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The direct hydroconversion of triglycerides into biojet fuel (i.e., cascade reactions including hydrogenation, deoxygenation, and hydrocracking) is challenging, even though it is beneficial in terms of process intensification. This is because the minute amount of CO produced during deoxygenation can poison the metal component of various metal–acid bifunctional catalysts, causing undesired overcracking and rapid catalyst deactivation through coke formation. To overcome this problem, we synthesized a CO-tolerant catalyst by supporting bimetallic PtRe on ultra-stable Y (USY) zeolite as acidic support. Compared to conventional catalyst (e.g., Pt/USY), PtRe/USY showed markedly enhanced tolerance to CO because it had weakened interaction with CO and also could rapidly convert the chemisorbed CO into less harmful methane and H2O through methanation. Consequently, overcracking and catalyst deactivation were greatly suppressed during the direct triglyceride hydroconversion. It is remarkable that PtRe/USY is intrinsically a much poorer hydrocracking catalyst than Pt/USY under pure H2 atmosphere because of its high hydrogenolysis activity. However, H2O and CO produced in situ during the deoxygenation of triglycerides selectively poisoned the active sites for undesired hydrogenolysis, thereby making PtRe/USY a highly stable and selective catalyst for producing biojet fuel. Under the optimum condition, 41 wt% of biojet fuel with respect to palm oil could be produced through direct hydroconversion, which satisfied all the required fuel specifications.

Protein synthesis is important for maintaining cellular homeostasis under various stress responses. In this study, we screened an anticancer drug library to select compounds with translational repression functions. AZD8055, an ATP-competitive mechanistic target of rapamycin complex 1/2 (mTORC1/2) inhibitor, was selected as a translational suppressor. AZD8055 inhibited protein synthesis in mouse embryonic fibroblasts and hepatocellular carcinoma HepG2 cells. Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) were activated during the early phase of mTORC1/2 inhibition by AZD8055 treatment. Combined treatment of AZD8055 with the MAPK kinase1/2 (MEK1/2) inhibitor refametinib or the p38 inhibitor SB203580 markedly decreased translation in HepG2 cells. Thus, the inhibition of ERK1/2 or p38 may enhance the efficacy of AZD8055-mediated inhibition of protein synthesis. In addition, AZD8055 down-regulated the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and AZD8055-induced phosphorylation of ERK1/2 and p38 had no effect on phosphorylation status of 4E-BP1. Interestingly, AZD8055 modulated the 4E-BP1 mRNA pool by up-regulating ERK1/2 and p38 pathways. Together, these results suggest that AZD8055-induced activation of MAPKs interferes with inhibition of protein synthesis at an early stage of mTORC1/2 inhibition, and that it may contribute to the development of resistance to mTORC1/2 inhibitors.

Deoxygenation of triglycerides (e.g., vegetable and microalgae oils) through hydro-upgrading is one of the most important routes to produce oxygen-free hydrocarbon fuels from biomass. Even though natural triglycerides are composed of fatty acids of different structures, their effects on catalytic selectivity and deactivation during deoxygenation have not been comprehensively investigated. In this study, we used three different reactant triglycerides including palm oil, soybean oil, and linseed oil for catalytic deoxygenation over Pt/γ-Al2O3. These oils consist of fatty acids with increasing degrees of unsaturation in the order of palm oil (number of C═C per fatty acid: 0.55) < soybean oil (1.33) < linseed oil (2.18). The catalytic results showed that the increased unsaturation of the triglycerides caused enhanced formation of heavy products by oligomerization (mostly dimers) of unsaturated fatty acid derivatives through Diels–Alder reaction and/or radical addition. These heavy products were readily transf...

Ketonization of fatty acids into fatty ketones is a potential route for producing high-value chemicals including bioderived lube base oil. In the present work, the catalytic selectivity and deactivation during the ketonization of C18 fatty acids having different unsaturation degrees over a TiO2 catalyst were rigorously investigated. The results demonstrated that the yield of fatty ketone gradually decreased with increasing unsaturation degree, while byproducts such as methyl ketones and olefins were produced owing to McLafferty rearrangement. It was verified that carboxylic acids longer than C5 can be decomposed via this pathway, the rate of which increased with the carbon chain length. In the ketonization of unsaturated fatty acids, the McLafferty rearrangement and cracking produced conjugated polyunsaturated olefins (e.g., dienes), which could be readily decomposed to coke. The results implied that the ketonization of natural fatty acids requires the presaturation of C═C bonds for increasing the fatty k...

Cooperative effects of secondary mesoporosity and zeolite crystallinity on the deactivation of ZSM-5 were investigated during propanal conversion. Varied secondary mesoporosities were introduced into a commercial ZSM-5 by alkaline desilication using solutions with different NaOH concentrations (0.1–0.5 M). The results showed that the mesoporosity gradually increased with the concentration of NaOH, while the intrinsic zeolitic microporosity decreased. This indicated that the alkaline desilication for mesopore generation is a destructive technique that sacrifices the zeolite crystallinity. In propanal conversion, ZSM-5 showed a longer catalyst lifetime as the external surface area increased (or as the zeolite framework thickness decreased) in the mild desilication regime (NaOH concentration ≤ 0.3 M). The enhanced catalyst lifetime could be attributed to the facilitated diffusion of coke precursors out of the zeolite structure. However, when the zeolite crystallinity or microporosity of ZSM-5 was decreased too much from excessively severe alkaline treatments (NaOH concentration > 0.3 M), deactivation of the catalyst became again faster. The result indicates that the crystallinity or the microporosity of ZSM-5 is also important in suppressing coke formation. This is in line with earlier reports showing that coke formation itself is a shape-selective reaction and significantly inhibited in the constrained space of the unique 10-membered micropore channels of ZSM-5. The present results imply that the generation of large mesoporosity (enhancing the diffusion of coke precursors) while keeping the zeolite crystallinity intact (suppressing coke formation by shape-selectivity) is highly desirable for designing a zeolite catalyst with an enhanced catalyst lifetime.

Hydroxypropyl cyclosophoraose-pullulan (HPCys-Pul) microspheres were designed as a novel hybrid system of biocompatible pullulan matrice and pendant hydroxypropyl cyclosophoraoses with drug complexing ability. The HPCys-Pul microspheres were prepared by emulsion crosslinking method, and characterized using thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, and solid state NMR spectroscopy. By virtue of hydroxypropyl cyclosophoraoses, the developed microspheres can encapsulate 4.2-fold more naproxen than pullulan microspheres. Korsmeyer–Peppas model was introduced for describing release kinetics. In vivo naproxen release analysis was carried out in Sprague-Dawley (SD) rats. From those results HPCys-Pul microsphere will be a promising platform for controlled drug delivery.

Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.

The cooperative effects of secondary mesoporosity and defects on the coke formation and deactivation of zeolite were investigated in n -pentane aromatization using model Ga/ZSM-5 catalysts. Mesoporosity was introduced to a commercial ZSM-5 by alkaline desilication, while the defects sites ( i.e. , internal silanols) in zeolites were annealed by the treatment with ammonium hexafluorosilicate. Aromatization after supporting Ga showed that the mesopore generation retarded catalyst deactivation via the suppression of internal coke formation while facilitating the external coke formation due to the enhanced diffusion of coke precursors (e.g ., alkylaromatics) out of zeolite micropores. Internal coke can cause a more severe deactivation than external coke because the acid sites are mainly located in the zeolite micropores. However, the mesopore generation alone could not efficiently reduce the total amount of coke deposition (it mainly changed the location of coke). In contrast, the annealing of internal silanols could suppress the overall coke formation. This phenomenon could be explained by the fact that coke precursors are initially generated at the zeolite internal defects, and then deposited as coke at either the internal or the external surfaces of the zeolite depending on the relative kinetics of coke precursor diffusion and its polymerization. Consequently, the catalyst with mesoporosity and annealed internal silanols exhibited the slowest catalyst deactivation due to the suppression of both internal and external coke depositions.

Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits tumor cell proliferation, inflammatory and oxidative stress better, when compared with other flavonoids. In the present study, it was demonstrated that luteolin induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic bodies. In addition, luteolin regulates expression of the endoplasmic reticulum (ER) chaperone binding immunoglobulin protein, activating ER stress sensors (eukaryotic initiation factor 2α phosphorylation and X‑box binding protein 1 mRNA splicing) and induced autophagy. The results indicated that luteolin induces the upregulation of the unfolded protein response pathway through the ER stress sensors, which helps as an influential regulator for the apoptosis pathway in PC12 cells. The results suggested that the understanding of the molecular mechanisms underlying luteolin‑induced apoptosis may be useful in cancer therapeutics, chemoprevention and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease.

BackgroundReactive oxygen species (ROS) produce different lesions in DNA by ROS-induced DNA damage. Detection and quantification of 8-oxo-7,8-dihydroguanine (8-oxoG) within cells are important for study. Human ribosomal protein S3 (hRpS3) has a high binding affinity to 8-oxoG. In this study, we developed an imaging probe to detect 8-oxoG using a specific peptide from hRpS3. Transactivator (TAT) proteins are known to have cell-penetrating properties. Therefore, we developed a TAT-S3 probe by attaching a TAT peptide to our imaging probe.ResultsA DNA binding assay was conducted to confirm that our probe bound to 8-oxoG and apurinic/apyrimidinic (AP) sites. We confirmed that the TAT-S3 probe localized in the mitochondria, without permeabilization, and fluoresced in H2O2-treated HeLa cells and zebrafish embryos. Treatment with Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, reduced TAT-S3 probe fluorescence. Additionally, treatment with O8, an inhibitor of OGG1, increased probe fluorescence. A competition assay was conducted with an aldehyde reaction probe (ARP) and methoxyamine (MX) to confirm binding of TAT-S3 to the AP sites. The TAT-S3 probe showed competitive binding to AP sites with ARP and MX.ConclusionsThese results revealed that the TAT-S3 probe successfully detected the presence of 8-oxoG and AP sites in damaged cells. The TAT-S3 probe may have applications for the detection of diseases caused by reactive oxygen species.

Pt/KL is a highly active and selective monofunctional catalyst for aromatization of n-alkanes due to its 1-dimensionally connected cage-like micropores. The unique micropore structure of the KL zeolite, however, can also inhibit the diffusion of bulky aromatic products out of the catalyst, which can cause unwanted side reactions that can decrease the aromatic yields. In this work, we investigated the effect of secondary mesoporosity, which can substantially facilitate molecular diffusion in Pt/KL during C6–C8 alkane aromatizations. The results showed that the hierarchically micro-/mesoporous Pt/KL synthesized with a subsequent dealumination/desilication method exhibited enhanced aromatic yields, compared with a conventional Pt/KL. In particular, in C7 and C8 aromatizations, the hierarchical Pt/KL showed substantially less formation of dealkylated aromatic products than the Pt/KL due to suppressed secondary hydrogenolysis. Pt supported on a solely mesoporous γ-Al2O3 also showed significantly suppressed secondary hydrogenolysis (dealkylation), which indicates that fast diffusion of alkylated aromatics out of the catalyst structure is important for suppressing the secondary hydrogenolysis. However, the solely mesoporous Pt/γ-Al2O3 showed markedly lower aromatization activities than the KL-supported catalysts, which indicates that Pt located inside the zeolite micropores is crucial for obtaining high catalytic activity due to the preorganization of n-alkanes in the micropores. The present results showed that the hierarchical Pt/KL provides the synergistically combined benefits of the Pt/KL and the mesoporous Pt catalyst, namely high aromatization activity and suppressed secondary hydrogenolysis, respectively.

2-Hydroxy-4-methoxy-2′,3′-benzochalcone (HymnPro), a chalcone derivative, induces cell cycle arrest at the G2/M phase followed by caspase-dependent apoptosis. Structurally, HymnPro contains a α-β olefin that can act as a Michael acceptor, and that is involved in the depletion of cellular glutathione. However, the effect of HymnPro on the generation of reactive oxygen species (ROS) is still unknown. In the present study, we observed that treatment of Capan-1 pancreatic cancer cells with HymnPro resulted in a dose-dependent accumulation of ROS, owing to the depletion of intracellular glutathione. Treatment with ROS scavenger N-acetylcycteine prevented HymnPro-induced caspase activation and cell death, but had little effect on G2/M cell cycle arrest and microtubule assembly. Our results suggest that HymnPro causes tubulin binding-mediated cell cycle arrest at the G2/M phase as well as ROS-mediated caspase activation.

Eupatorin (5,3′-dihydroxy-6,7,4′-trimethoxyflavone) is a natural flavone exhibiting antiproliferative activity in diverse cancer cell lines. In the present study, we characterized the cytotoxic effect of eupatorin in HeLa cervical carcinoma cells. Treatment with eupatorin induced cell cycle arrest at the G2/M phase within 12 h, followed by the induction of apoptosis. Eupatorin down-regulated cyclin D1 within 3 h, whereas up-regulated cyclin B1 levels after 12 h. Eupatorin also accumulated p53, p21, and Bax levels and stimulated the cleavage of caspase-3, caspase-7, and poly(ADP-ribose) polymerase after 12 h of treatment. In addition, we found that eupatorin-induced p21 expression was p53-dependent, while Bax expression was Egr-1-dependent pathway. Our results suggest that eupatorin induces G2/M cell cycle arrest through dysregulation of cell cycle regulatory proteins and triggers apoptosis through activation of the p53-dependent and p53-independent pathways.

A methoxylated flavanone derivative, 2′,3′,4′-trimethoxy-5,6-naphthoflavanone (TMNF), was synthesized, and its anti-proliferative activity was evaluated. In HCT116 colon cancer cells, TMNF inhibited cellular proliferation and triggered cytotoxicity. A flow cytometry assay showed that TMNF caused cell cycle arrest at the G2/M phase with a concomitant decrease in the population of G1 phase cells. Furthermore, TMNF caused accumulation of p53 and its downstream target, Bax, and stimulated cleavage of caspase-7 and poly(ADP-ribose) polymerase. These data suggest that methoxylated naphthoflavanone can be an attractive pharmacophore for further development of therapeutic adjuvants.

Eukaryotic translation initiation factor 2 alpha (eIF2α), which is a component of the eukaryotic translation initiation complex, functions in cell death and survival under various stress conditions. In this study, we investigated the roles of eIF2α phosphorylation in cell death using the breast cancer cell lines MCF-7 and MCF-7/ADR. MCF-7/ADR cells are MCF-7-driven cells that have acquired resistance to doxorubicin (ADR). Treatment of doxorubicin reduced the viability and induced apoptosis in both cell lines, although susceptibility to the drug was very different. Treatment with doxorubicin induced phosphorylation of eIF2α in MCF-7 cells but not in MCF-7/ADR cells. Basal expression levels of Growth Arrest and DNA Damage 34 (GADD34), a regulator of eIF2α, were higher in MCF-7/ADR cells compared to MCF-7 cells. Indeed, treatment with salubrinal, an inhibitor of GADD34, resulted in the upregulation of eIF2α phosphorylation and enhanced doxorubicin-mediated apoptosis in MCF-7/ADR cells. However, MCF-7 cells did not show such synergic effects. These results suggest that dephosphorylation of eIF2α by GADD34 plays an important role in doxorubicin resistance in MCF-7/ADR cells.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovitis, hyperplasia, and the destruction of bone and cartilage. A variety of immunosuppressive biological agents have been developed because the pathogenesis of RA is related predominantly to the inflammatory response. However, rheumatoid arthritis fibroblast-like synovial cells (RAFLS), which are known to play an important role in RA progression, exhibit resistance to immunosuppressants through cancer-like properties. In this study, we identified a novel therapeutic compound for RA, which reduced inflammation and the abnormal proliferation of RAFLS in natural product library made from Korean native plants. Eupatorium japonicum Thunb. (EJT) extract, a component of the natural product library, most effectively reduced viability through the induction of ROS-mediated apoptosis in a dose-dependent manner. In addition, the increased ROS induced the expression of ATF4 and CHOP, key players in ER stress-mediated apoptosis. Interestingly, EJT extract treatment dose-dependently reduced the expression of IL-1β and the transcription of MMP-9, which were induced by TNF-α treatment, through the inhibition of NF-κB and p38 activation. Collectively, we found that EJT extract exerted apoptotic effects through increases in ROS production and CHOP expression and exerted anti-inflammatory effects through the suppression of NF-κB activation, IL-1β expression, and MMP-9 transcription.

Historically, Pt/LTA (e.g., Pt/NaA) has often been used as a model catalyst for studying the catalytic functions of hydrogen spillover (H spillover). Notably, none of the works reported appreciable catalytic activities for Pt/LTA alone, while markedly enhanced activities were reported after physical dilution with some acidic oxides. It was often speculated without experimental evidence that activated hydrogen generated from Pt/LTA can migrate to the diluents surface (“inter-particular” H spillover) where organic reactants can react with spilt-over hydrogen. In this work, we carefully studied benzene hydrogenation activities of Pt/NaA and its decationized form (Pt/HA), before and after the physical dilution with various metal oxides possessing different Lewis and Bronsted acidity. The originally negligible activity of Pt/NaA increased significantly after mixing with various acidic oxides. The physical dilutions, however, resulted in a significant alteration of Pt/NaA structure due to solid-state H+ exchange, which made the catalytic interpretation vague. In contrast, Pt/HA structure did not change after the dilutions, and thus could be used as an ideal catalytic model system for studying inter-particular H spillover. The catalytic results showed that Al-rich metal oxides with abundant Lewis acid sites are effective for enhancing the catalytic activity.

Two different methods, organosilane templating and carbon templating, were used to generate secondary mesoporosity within SAPO-11. The former method produced mesoporous SAPO-11 samples with a large amount of external acidity, while the latter produced mesoporous samples containing predominantly internal acid sites. It was shown that, depending on the location of Bronsted acid sites, Pt supported on mesoporous SAPO-11 samples can exhibit widely ranging maximum isomerization yields from 13% to 84%, while solely microporous SAPO-11 showed 44% isomerization yield. The results indicate that the presence of secondary mesoporosity can be either remarkably beneficial or detrimental to hydroisomerization selectivity depending on the spatial location of the acid sites. The present results clearly showed that hydroisomerization selectivity of the catalysts can be significantly enhanced by facilitating the hydrocarbon diffusion via the formation of secondary mesopores while suppressing the formation of external acid sites that can non-selectively catalyze consecutive cracking reactions.

BACKGROUND IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end-stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope. MATERIALS AND METHODS We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first-year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners. RESULTS Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m2 , which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/gCr, respectively, P

Ethnopharmacological relevance The medicinal efficacy of hempseed (Cannabis sativa L.), which is rich in polyunsaturated fatty acids, in atopic dermatitis, inflammation, and rheumatoid arthritis (RA) has been suggested for centuries. Hempseed has been used as a treatment for these diseases in Korean and Chinese folk medicine. The aim of the study is to investigate the effects of hempseed oil (HO) on MH7A human RA fibroblast-like synovial cells. Materials and methods MH7A cells were used to study the anti-rheumatoid effects of hempseed (Cannabis sativa L., cv. Cheungsam/Cannabaceae) oil by investigating cell viability, apoptosis, lipid accumulation, oxidative stress, and endoplasmic reticulum (ER) stress-induced apoptosis. Results HO treatment reduced the survival rate of MH7A cells and promoted apoptotic cell death in a time- and dose-dependent manner. Both lipid accumulation and the level of intracellular reactive oxygen species (ROS) increased in HO-treated MH7A cells. Co-treatment with the antioxidant Tiron effectively abrogated the cytotoxic effects of HO; the ROS level was reduced, cell viability was recovered, and apoptotic cell death was significantly diminished. Moreover, HO-treated cells exhibited increased expression of the major ER stress markers, glucose-regulated protein 78 and C/EBP homologous protein (CHOP). The siRNA-mediated knockdown of CHOP prevented HO-induced apoptosis. Conclusions Our results suggest that HO treatment induced lipid accumulation, ROS production, CHOP expression, and apoptosis in MH7A cells, and that CHOP functions as an anti-rheumatoid factor downstream of HO in MH7A cells.

Plasma cells are exposed to intense endoplasmic reticulum (ER) stress imposed by enormous rates of immunoglobulin (Ig) synthesis and secretion. Therefore, protein homeostasis is crucial for the survival of plasma cells, but its molecular mechanism remains largely unknown. Here we found marked overexpression of FK506-binding protein 13 (FKBP13) in long-lived plasma cells from autoimmune mice, and investigated its function using a plasmacytoma cell line secreting IgA. FKBP13 expression was induced largely in the lumen of ER in response to treatment with an ER stressor tunicamycin or overexpression of an adaptive unfolded protein response protein X-box binding protein 1 (XBP1). Silencing of FKBP13 expression led to induction of molecules involved in the terminal unfolded protein response and ER stress-associated apoptosis. FKBP13 interacted with Ig, facilitated its ubiquitination, and lowered the extent of ER stress. FKBP13 overexpression caused a significant reduction in secreted IgA in plasmacytoma cells, and FKBP13 knockdown exerted an opposite effect. Rapamycin interfered with the interaction between FKBP13 and IgA and enhanced the amount of secreted IgA. Importantly, the level of FKBP13 was inversely correlated with the amount of secreted antibody in long-lived plasma cells from autoimmune mice. These results suggest that FKBP13 is a marker of long-lived plasma cells and a component of XBP1-dependent ER protein homeostasis. FKBP13 is likely to act as a molecular chaperone that delivers misfolded ER clients, including Ig, to ER-associated degradation, so reducing proteotoxic stress on the plasma cell. Our data reveal a novel cytoprotective role for FKBP13 in long-lived plasma cells occurring at the expense of antibody production.

Non-motile primary cilium is an antenna-like structure whose defect is associated with a wide range of pathologies, including developmental disorders and cancer. Although mechanisms regulating cilia assembly have been extensively studied, how cilia disassembly is regulated remains poorly understood. Here, we report unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1) in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143 and T224 in a manner that requires both non-canonical Wnt5a ligand and casein kinase 1 epsilon (CK1ɛ), and that this event is critical to interact with Plk1 in early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a-CK1ɛ-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold and activating its associated Aurora-A (AurA), a kinase crucially required for primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1 plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders.

Fibroblast-like synovial cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA), as these cells are involved in inflammation and joint destruction. Apigenin, a dietary plant-flavonoid, is known to have many functions in animal cells including anti-proliferative and anticancer activities, but its role in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) has not been reported. In this study, we investigated the roles of apigenin in RA-FLSs. The survival rate decreased, and apoptotic cell death was induced by apigenin treatment in RA-FLSs. Apigenin treatment resulted in activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and pretreatment with an ERK inhibitor PD98059 dramatically reduced apigenin-induced apoptosis. We found that apigenin-mediated production of a large amount of intracellular reactive oxygen species (ROS) caused activation of ERK1/2 and apoptosis; treatment with the antioxidant Tiron strongly inhibited the apigenin-induced generation of ROS, phosphorylation of ERK1/2, and apoptotic cell death. Apigenin-induced apoptotic cell death was mediated through activation of the effectors caspase-3 and caspase-7, and was blocked by pretreatment with Z-VAD-FMK (a pan-caspase inhibitor). These results showed that apigenin-induced ROS and oxidative stress-activated ERK1/2 caused apoptotic cell death in apigenin-treated RA-FLSs.

Macrophages secrete inflammatory cytokines and mono-nitrogen oxide (NO), and play crucial roles in inflammation in early-stage rheumatoid arthritis (RA). This study investigated whether glucosamine hydrochloride (GlcN), a nonsteroidal anti-inflammatory agent (NSAID) widely used to treat arthritis, affects the expression of inflammatory cytokines via the unfolded protein response (UPR) in lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW264.7 cells). Pretreatment with GlcN reduced the expression of inflammatory cytokines and inhibited cell differentiation. Moreover, GlcN treatment increased the expression of CHOP and BiP/Grp78, the UPR target genes, in the presence or absence of LPS. Indeed, knockdown of CHOP using siRNAs prevented the GlcN-mediated reduction of inflammatory cytokines in LPS-stimulated RAW264.7 cells. Finally, we found that GlcN-mediated induction of CHOP reduced the phosphorylation of JNK and NF-?B in LPS-stimulated RAW264.7 cells. Combined, these results suggest that the GlcN-mediated induction of CHOP negatively regulates the inflammatory response by modulating JNK and NF-?B in LPS-stimulated RAW264.7 cells.

Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca2+ leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.

For many years, HBTs have been vertically and laterally scaled down to improve high-frequency performance. For the very small devices of recent process, some parameters cannot be scaled down properly and an alternative scaling-law is required. In this paper, we describe the optimization issues for high-speed InP/InGaAs SHBTs and offer a design guideline to accommodate the scaling limit. From a 0.25 μm SHBT designed by the scaling law, the maximum extrapolated f max of about 687 GHz with f T of 215 GHz can be achieved. We also investigate the effect of key geometrical parameters such as emitter geometry and base/collector layer thicknesses on the device RF performance.

It is well known that C/sub bc/ is the dominant nonlinear element in heterojunction bipolar transistors (HBTs). To study its behavior, an analytical nonlinear HBT equivalent-circuit model has been developed. The present model includes the effect of the ionized donor charge in the depleted collector region compensated by the injected mobile charge. The model-based simulation shows that, at a small-signal range, the third-order intermodulation (IM3) of the normal HBT has the normal 3:1 gain slope generated by the nonlinearity of C/sub bc/. At a large-signal level, the load line passes through some regions with constant C/sub bc/ because its collector is fully depleted by the injected free carriers, and the growth rate of the IM3 is decreased. The punch-through collector HBT has constant C/sub bc/ during the whole RF cycle, and the IM3, which is generated by g/sub m/ nonlinearity, has the normal 3:1 gain slope for the all input signal level. Therefore, the IM3 level is significantly lower for the punch-through HBT at a low-power level, but the IM3s of both devices are comparable at a high-power level. The experiment supports our proposed model.

Pb(Zr,Ti)O3 (PZT) thin films were deposited using a liquid delivery metalorganic chemical vapor deposition (MOCVD) system. A novel Zr precursor, Zr(DIBM)4/ THF, was used as a Zr source, and Pb(DPM)2/THF and Ti(O/Pr)2(DPM)2/THF were used as Pb and Ti sources, respectively. These liquid sources were simultaneously injected into a vaporizer heated at 270°C. The vaporized gas was transported to a reactor by N2 carrier gas and blowed on 6” substrate area heated at 550°C with O2 gas through a shower head. In a preliminary experiment, it was found that the deposition rate of ZrO2 thin films was relatively high and limited by the amount of supplying source material at the substrate temperature above 500°C in case of Zr(DIBM)4/THF while it was low and limited by reaction even at 600°C in case of Zr(DPM)4/THF. The PZT 35/65 thin films with a thickness of 440 nm exhibited good ferroelectric properties: 2Pr of 70 μC/cm2 and 2E c of 140 kV/cm. The deposition rate of the PZT films was approximately 11 nm/min a...

In this study, the effect of the emitter-base contact spacing on the current gain of InGaP/GaAs HBTs has been described and the base contact recombination current has been experimentally studied. When devices were passivated by nitride, the current gain of InGaP/GaAs HBTs showed no variation with the perimeter to area ratio, which suggested that the surface recombination current of InGaP/GaAs HBTs was negligible, leading the base contact recombination current to affect the current gain. It was found that the base contact recombination current significantly degraded the current gain when the emitter-base contact spacing was reduced to below 0.5 μm. The diode equation was used to model the base contact recombination current, and an ideality factor of 1.76 was obtained.

New fluoroalkylated end-capped 2-acrylamido-2-methylpropanesulfonic acid copolymers containing poly(oxyethylene) units were prepared by the use of fluoroalkanoyl peroxides. It was demonstrated that these fluorinated copolymers can form gels in DMSO under non-crosslinked conditions, and these fluorinated polymeric gelling electrolytes containing lithium salts exhibit a considerably high ionic conductivity of 10 −3 S/cm level at room temperature.

New fluoroalkyl end-capped oligomers containing pendant phosphoric acid groups wereprepared by the reactions of the corresponding monomer with fluoroalkanoyl peroxides. It was demonstrated that not only strong aggregations of fluoroalkyl segments but also hydrogen bonding could interact synergistically to form the highly viscoelastic fluids (gel-like fluids) in aqueous solutions of these new fluoroalkyl end-capped oligomers containing pendant phosphoric acid groups. Furthermore, these oligomers were able to reduce the surface tension of water effectively to exhibit a clear breakpoint resembling a CMC, and the modified stainless-steel surface treated with these oligomers was shown to possess an excellent property imparted by fluorine. More interestingly, these oligomers were found to be potent and selective inhibitors against HIV-1 replication in vitro. New fluoroalkyl end-capped phosphonic acid and phosphonate oligomers were also prepared by the reactions of the corresponding phosphonic acid and phosphonate monomers, respectively, by the use of fluoroalkanoyl peroxides. These new fluoroalkyl end-capped phosphonic acid and phosphonate oligomers were found to have a higher solubility in not only water but also in common organic solvents than that of the corresponding fluorinated oligomers containing pendant phosphoric acid groups, and these new oligomers were able to reduce the surface tension of these solvents quite effectively. Thus, these oligomers are expected to develop as new fluorinated oligosurfactants. Moreover, the modified poly(methyl methacrylate) surface treated with these phosphonate oligomers was clarified to exhibit a good oil-repellency imparted by fluorine. In addition, fluoroalkyl end-capped phosphonate homo- and cooligomers were found to form monomolecular films at the air–water interface. Therefore, these fluorinated oligomers are suggested to have high potential for new functional materials through not only their excellent properties imparted by both fluorine and phosphorus, but also through their biological properties. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 228–245, 2001

New fluoroalkylated end-capped co-oligomers containing oligo (oxyethylene) units were prepared by reactions of fluoroalkanoyl peroxides with oligo (oxyethylene) units -containing vinylsilane (or methacrylates) and co-monomers such as acrylic acid, dimethylacrylamide and isopropylacry-lamide. By these fluorinated co-oligomers containing oligo (oxyethylene) units, the surface tension of water could be reduced effectively with a clear break point resembling CMC and appeared to be formed intra- or inter molecular aggregates resembling micelles in water. The co-oligomers containing oli-go (oxyethylene) units were found useful for extracting various metal cations and oligomer electrolyte film containing LiCF3SO3 showed high ionic conductivity of 4×10-5S/cm at room temperature. Of particular interest is the finding that the fluoroalkylated end-capped acrylic acid co-oligomers containing oligo (oxyethylene) units were found to strongly and selectively inhibit HIV-1 replication in vitro.

InP-based single heterojunction bipolar transistors (SHBTs) for high-speed circuit applications were developed. Typical common emitter DC current gain (/spl beta/) and BV/sub CEO/ were about 17 and 10 V, respectively. Maximum extrapolated f/sub max/ of 478 GHz with f/sub T/ of 154 GHz was achieved for 0.5 /spl times/ 10 /spl mu/m/sup 2/ emitter size devices at 300 kA/cm/sup 2/ collector current density and 1.5 V collector bias. This is the highest f/sub max/ ever reported for any nontransferred substrate HBTs, as far as the authors know. This paper highlights the optimized conventional process, and the authors have great hopes for the process that offers inherent advantages for the direct implementation to high-speed electronic circuit fabrication.

A MMIC chip set consisting of a power amplifier, a driver amplifier, low noise amplifier, and a frequency doubler has been developed for automotive radar systems at 77GHz. The chip set was fabricated using 0.15 /spl mu/m gate-length InGaAs/InAlAs/GaAs mHEMT process based on 4-inch substrate. The power amplifier demonstrated a measured small signal gain of over 20 dB from 76-77GHz with 15.5 dBm output power. The chip size is 2mm /spl times/ 2mm. The driver amplifier exhibited a gain of 23dB over a 76-77 GHz band with an output power of 13dBm. The chip size is 2.1mm /spl times/ 2mm. The low noise amplifier achieved a gain of 20 dB in a band between 76-77GHz with an output power of 10 dBm. The chip size is 2.2mm /spl times/ 2mm. The frequency doubler achieved an output power of -6 dBm at 76.5 GHz with a conversion gain of -16dB for an input power of 10 dBm and a 38.25 GHz input frequency. The chip size is 1.2 mm /spl times/ 1.2mm. This MMIC chip set is suitable for the 77 GHz automotive radar systems and related applications in W-band.

In this study, we investigated the effects of long-term administration of quercetin with or without daidzein on glutathione and the enzymes involved in its metabolism in rat liver in vivo. Male Sprague-Dawley rats were divided randomly into four groups and given oral quercetin (20 mg/day) and daidzein (20 mg/day) alone or in combination, or vehicle alone for six weeks. The serum and liver alpha-tocopherol concentrations were significantly increased following administration of quercetin and daidzein alone or in combination. Glutathione concentration and glutathione reductase activity was significantly (p0.05) decreased with quercetin treatment, while no such effect was observed with daidzein treatment. Interestingly, decrease in glutathione concentration and glutathione reductase activity by quercetin treatment was inhibited by combined administration of daidzein and quercetin. The malondialdehyde concentration was significantly decreased following administration of quercetin and daidzein alone or in combination. These results suggest that quercetin, but not daidzein, acts as a pro-oxidant agent by decreasing glutathione concentration and glutathione reductase activity. Interestingly, this pro-oxidant effect of quercetin was inhibited by the combined administration of quercetin and daidzein.

A significant degradation of current gain of InP/InGaAs/InP double heterojunction bipolar transistors was observed after passivation. The amount of degradation depended on the degree of surface exposure of the p-type InGaAs base layer according to the epi-structure and device structure. The deposition conditions such as deposition temperature, kinds of materials (silicon oxide, silicon nitride and aluminum oxide) and film thickness were not major variables to affect the device performance. The gain reduction was prevented by the BOE treatment before the passivation. A possible explanation of this behavior is that unstable non-stoichiometric surface states produced by excess In, Ga, or As after mesa etching are eliminated by BOE treatment and reduce the surface recombination sites.

The 0.2 /spl mu/m gate-length power MHEMTs with the wide head T-shaped gate are characterized for DC, microwave, and noise performance. The MHEMT device shows the DC output characteristics having an extrinsic transconductance of 700 mS/mm and a threshold voltage of -0.92 V. The f/sub T/ and f/sub max/ obtained for the 0.2 /spl mu/m /spl times/ 100 /spl mu/m MHEMT device are 120 GHz and 230 GHz, respectively. The MHEMTs exhibit the minimum noise figure, NF/sub min/, of 1.26 dB and associated gain of 8.6 dB at 30 GHz. The NF/sub min/ measured at 35 GHz is 1.45 dB with associated gain of 7.5 dB. This noise data is first reported for power MHEMT devices with InGaAs channel of 53% In. These excellent noise characteristics can be explained by the drastic reduction of gate resistance owing to the T-shaped gate with a wide head of about 1.2 /spl mu/m and the improved device performance.

We have investigated the effects of the cleaning process prior to selective reoxidation on the device reliability against hot carrier degradation. A remarkable increase in the lifetimes was obtained for the devices in which the remaining oxide under the LDD spacer was partially removed. This additional cleaning process was found to effectively improve the interface quality of the spacer bottom oxide.

We have investigated the various types of diffusion barriers for the thermally stable W-bit line structure. We estimated the thermal stability and the electrical characteristics of various barrier structures after annealing at 850/spl deg/C and then optimized the W-bit line process. A newly developed PVD-Ti/PVD-TiN/RTP/Strip/PVD-TiN/CVD-W structure showed good integrity with the W-bit line after high temperature processing. It is concluded that the prevention of oxygen penetration during silicidation is most important for the formation of a uniform silicide layer and better contact characteristics.

PURPOSE The purpose of this study was to investigate topographic characteristics of the retina in myopic eyes. METHODS We reviewed spectral-domain optical coherence tomography (SD-OCT) images of patients with myopia retrospectively. Retinal topography (RT) was defined as the topography of the retinal pigment epithelium layers. Retinal topographies were classified into several types, and the distribution and characteristics of each type were assessed in eyes with varying degrees of axial length (AL). RESULTS A total of 167 subjects with myopia were included in this study. Seventy eyes (41.9%) were classified as regular (R) type, 48 (28.7%) were wave (W) type, 32 (19.2%) were band (B) type, and 17 (10.2%) were pond (P) type. The distribution of these types varied significantly among eyes with different degrees of AL (P < 0.001); R-type was predominant in eyes with 24 mm less than or equal to AL less than 26 mm, and P-type in eyes with AL greater than or equal to 28 mm. The retina sloped away from the cornea more frequently on the nasal side than it did on the temporal side or in between the nasal and the temporal sides, with the exception of the P-type RT. Topography of the central zone was frequently slanted, except in B-type eyes. The difference between the refractive and corneal astigmatism of eyes with P-type RT was greater than that of B-type eyes (P = 0.002). CONCLUSIONS Retinal topography varies according to the degree of AL. This variation in RT may originate from the differences between healthy eyes and highly myopic eyes, and may be related to the optical characteristics of the eye.

A new layout for high-speed AlGaAs/GaAs heterojunction bipolar transistors (HBTs) is presented. The layout is horseshoe shaped and designed to simultaneously reduce base resistance (R/sub B/) and base-collector capacitance (C/sub BC/). A horseshoe-shaped HBT and a conventional single-finger HBT with the same emitter width of 2 /spl mu/m were fabricated and tested. The reduction of R/sub B/ and C/sub BC/ using the horseshoe-shaped HBT resulted in a 25% improvement of the maximum oscillation frequency (f/sub max/=130 GHz).