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Abstract Background The measurement of native T1 through cardiovascular magnetic resonance (CMR) is a noninvasive method of assessing myocardial fibrosis without gadolinium contrast. No studies so far have evaluated native T1 after renal transplantation. The primary aim of the current study is to assess changes in the myocardium native T1 6 months after renal transplantation. Methods We prospectively evaluated 44 renal transplant patients with 3 T CMR exams: baseline at the beginning of transplantation and at 6 months after transplantation. Results The native T1 time was measured in the midventricular septum and decreased significantly from 1331 ± 52 ms at the baseline to 1298 ± 42 ms 6 months after transplantation (p = 0.001). The patients were split into two groups through a two-step cluster algorithm: In cluster-1 (n = 30) the left ventricular (LV) mass index and the prevalence of diabetes were lower. In cluster-2 (n = 14) the LV mass index and diabetes prevalence were higher. Decrease in native T1 values was significant only in the patients in cluster-1 (p = 0.001). Conclusions The native myocardial T1 time decreased significantly 6 months after renal transplant, which may be associated with the regression of the reactive fibrosis. The patients with greater baseline LV mass index and the diabetic group did not reach a significant decrease in T1.

Litter input is a critical link between the circulation and flows of energy and matter in forest ecosystems. Drought events impact litter inputs, affecting forest ecosystems’ nutrient and energy cycles. To investigate the response of litter production to extreme drought, explore their recovery mechanism, and the difference between whole year, concurrent drought, non-drought period, rainy season, and dry season. We studied an extreme drought event in a subtropical evergreen broadleaved forest in the Ailao Mountain in 2009–2010. We used 10 years (2005–2014) of monthly litter production and climate data, including monthly average precipitation (MAP), soil water content (SWC), and monthly average temperature (MAT). The observation period was separated into pre-drought (2005–2008), during-drought (2009–2010), and post-drought (2011–2014) periods. We found that annual total litter production decreased by 12 % during the drought (p

Summary: Retinoic acid (RA) counters insulin’s metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-induced CYP26A1 transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppresses CYP26A1 expression, increasing RA’s elimination half-life. Interaction between CCAAT-enhancer-binding protein beta (C/EBPβ) and the major allele of SNP rs2068888 enhances CYP26A1 expression; the minor allele restricts the C/EBPβ effect on CYP26A1. The major and minor alleles associate with impaired human health or reduction in blood triglycerides, respectively. Thus, regulating CYP26A1 transcription contributes to adapting RA to coordinate energy availability with metabolism. These results enhance insight into CYP26A1 effects on RA during changes in energy status and glucocorticoid receptor modification of RAR-regulated gene expression.

This article contains data on subsidies provided to the fisheries sector by maritime countries. The dataset is the culmination of extensive data collection efforts using peer-reviewed and grey literature, national budgets, online databases, websites and other relevant sources (e.g. OECD, World Bank and WTO), in order to estimate the scope and magnitude of global fisheries subsidies. For subsidies where we found evidence of expenditure by a country, we record the total amount alongside the source references and refer to these as ‘reported’ data. Where evidence is found that a country provides a subsidy but no amount reported, we estimate using various approaches and refer to these as ‘modeled’ data. Where evidence exists that no subsidy is provided by a country we refer to these null values as ‘not found evidence of subsidy’. All amounts were converted to constant 2018 USD using 2017 exchange rates and annual Consumer Price Index averages. The final dataset of ‘reported’, ‘modeled’ and ‘not found’ subsidies for 2018 consists of 13 subsidy types across 152 maritime countries. The dataset, first developed in the early 2000s, now forms part of the global fisheries management infrastructure and is a central tool used by WTO negotiators. The data we provide may be used to support local, regional and global fisheries management decision-making and may have further uses when analysed in combination with other fisheries related data. Interpretation of these data can be found in the associated research article titled “Updated estimates and analysis of global fisheries subsidies” [1]. Keywords: World Trade Organization, Fisheries, Subsidies, Capacity-enhancing, Overcapacity, Overfishing, Fuel subsidies, Fisheries management

Predicting radioactive fission product (FP) behaviors in the reactor coolant system and the containment of a nuclear power plant (NPP) is one of the major concerns in the field of reactor safety, since the amount of radioactive FP released into the environment during the postulated accident sequences is one of the major regulatory issues. Radioactive FPs circulating in the primary coolant loop and released into the containment are basically in the form of gas or aerosol. In this study, a multi-component and multi-sectional analysis module for aerosol fission products has been developed based on the MAEROS model [1,2], and the aerosol transport model has been developed and verified against an analytic solution. The deposition of aerosol FPs to the surrounding structural surfaces is modeled with recent research achievements. The developed aerosol analysis model has been successfully validated against the STORM SR-11 experimental data [3], which is International Standard Problem No. 40. Future studies include the development of the resuspension, growth, and chemical reaction models of aerosol fission products.

A new computer code, named CORONA (Core Reliable Optimization and thermo-fluid Network Analysis), was developed for the core thermo-fluid analysis of a prismatic gas cooled reactor. The CORONA code is targeted for whole-core thermo-fluid analysis of a prismatic gas cooled reactor, with fast computation and reasonable accuracy. In order to achieve this target, the development of CORONA focused on (1) an efficient numerical method, (2) efficient grid generation, and (3) parallel computation. The key idea for the efficient numerical method of CORONA is to solve a three-dimensional solid heat conduction equation combined with one-dimensional fluid flow network equations. The typical difficulties in generating computational grids for a whole core analysis were overcome by using a basic unit cell concept. A fast calculation was finally achieved by a block-wise parallel computation method. The objective of the present paper is to summarize the motivation and strategy, numerical approaches, verification and validation, parallel computation, and perspective of the CORONA code.

Objective: To investigate the clinical features of patients with definite vestibular migraine (dVM). Methods: A total of 91 patients with vestibular symptoms accompanied by migraines/migraine-like symptoms were enrolled and diagnosed according to the criteria of the Bárány Society and the International Headache Society. Baseline data were collected. Videonystagmography and immune-related laboratory tests were performed. Results: Among the 91 patients, 62 (68.1%) had dVM (11 men, 51 women). Among dVM patients, migraine occurred earlier than vestibular symptoms in 42 (67.7%) patients. Spontaneous vertigo occurred in 41 (66.1%) patients. Induced vertigo occurred in 21 (33.9%) patients. Motion sickness occurred in 33 (53.2%) patients. Central oculomotor dysfunction was observed in 11 (17.7%) patients. Caloric test revealed unilateral horizontal semicircular canal dysfunction in 12 (19.4%) patients. Severe intolerance during the test occurred in 44 (71.0%) patients with dVM. 12 (19.4%) patients showed abnormal immune-related indicators. Conclusion: dVM is more common in women. The onset of migraine precedes that of vestibular symptoms, which are often accompanied by photophobia and phonophobia. Motion sickness and severe caloric test intolerance can contribute to the diagnosis of dVM. Immunological indicators are abnormal in some patients with dVM, dVM may be secondary or an accompanying disorder, but the causal relationship needs further investigation. Level of evidence: IV.

Deep eutectic solvents (DES) are renowned for their effectiveness in deconstructing lignocellulose and extracting lignin, yet the challenges lie in lignin condensation and the disposal of the DES remnants after pretreatment. To overcome these issues, this work proposed a holistic strategy utilizing deep eutectic solvent (DES)-driven lignocellulose deconstruction to upgrade lignocellulose into nitrogen-doped carbon dots (CDs) and iron-decorated porous carbons, serving as photocatalysts and adsorbents, respectively. These nitrogen-doped CDs via the choline chloride/FeCl 3 DES pretreatment exhibited abundant nitrogen/oxygen functional groups, enhancing photocatalytic activities and facilitating effective charge separation and transfer. The photocatalytic efficiency of the CDs on dyes reached 97 % under acidic conditions primarily, and free radical quenching experiments indicated that singlet oxygen was the dominant oxidant species. Moreover, the adsorption capabilities of Fe-decorated porous carbons for Congo red reached 2432.3 mg·g -1 , surpassing most existing carbon materials. The adsorption mechanism was due to a synergistic effect including physical adsorption, coordination, hydrogen bonding, electrostatic, and π-π interactions. This study proposed a synergetic conversion of DES and lignocellulose into functional carbon materials for wastewater remediation, which inspired the development of a green and cost-effective biorefinery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

To comprehend the biosynthesis processes of conifers, it is essential to investigate the disparity between the cell wall shape and the interior chemical structures of polymers throughout the development of Chinese pine. In this study, branches of mature Chinese pine were separated according to their growth time (2, 4, 6, 8 and 10 years). The variation of cell wall morphology and lignin distribution was comprehensively monitored by scanning electron microscopy (SEM) and confocal Raman microscopy (CRM), respectively. Moreover, the chemical structures of lignin and alkali-extracted hemicelluloses were extensively characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The thickness of latewood cell walls increased steadily from 1.29 μm to 3.38 μm, and the structure of the cell wall components became more complicated as the growth time increased. Based on the structural analysis, it was found that the content of β-O-4 (39.88-45.44/100 Ar), β-β (3.20-10.02/100 Ar) and β-5 (8.09-15.35/100 Ar) linkages as well as the degree of polymerization of lignin increased with the growth time. The complication propensity increased significantly over 6 years before slowing to a trickle over 8 and 10 years. Furthermore, alkali-extracted hemicelluloses of Chinese pine mainly consist of galactoglucomannans and arabinoglucuronxylan, in which the relative content of galactoglucomannans increased with the growth of the pine, especially from 6 to 10 years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Vitamin D is an important immune modulator and is associated with susceptibility to infection. However, past studies have reported inconsistent results regarding the association between vitamin D deficiency and mortality in patients with sepsis, and early-stage data regarding septic shock are limited. This study aimed to determine the relationship between vitamin D deficiency on admission to the emergency department (ED) and mortality in patients with septic shock., Methods: We analyzed prospectively collected data on adult patients with septic shock who were treated with protocol-driven resuscitation bundle therapy in the ED between September 2019 and February 2021. Septic shock was defined by the sepsis-3 definition and vitamin D deficiency was defined as a 25-hydroxyvitamin D <20 ng/ml. The primary outcome was 30-day mortality., Results: A total of 302 patients were included, 236 (78.1%) patients had vitamin D deficiency; it was significantly higher in non-survivors than in survivors (89.3% vs. 73.9%, P = 0.004). Mortality was higher in vitamin D deficient patients than in non-deficient patients (31.8% vs. 13.6%, P = 0.004). In multivariate analysis, vitamin D deficiency (odds ratio [OR], 2.43; 95 % confidence interval [CI], 1.03-5.74), hyperlactatemia (OR, 3.65; 95 % CI, 1.95-6.83), Sequential Organ Failure Assessment scores (OR, 1.22; 95% CI, 1.09-1.36), and albumin levels (OR, 0.39; 95% CI, 0.21-0.73) were significantly associated with 30-day mortality., Conclusions: Vitamin D deficiency was prevalent in patients with septic shock visiting the ED and was associated with mortality., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Understanding of the morphological changes at different growth stages and lignin accumulation pattern for pine biomass plays the key role in facilitating the further development of value-added utilization and downstream conversion processes. This work systematically revealed the morphological change and lignin accumulation pattern in Chinese pine branches cell walls via confocal Raman microscopy (CRM) technology. Meanwhile, the structural characteristics of isolated lignin samples from different growth stages were synthetically characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques. The results indicated that the content of pith in adult pine new branch was bigger than juvenile trees. With the increase of physiological age, the branches in adult pine could accumulate more lignin both in overall content and the concentration of cell corner middle layer. Moreover, the significantly increases of molecular weights and the β-O-4, β-β linkages content revealed that the lignin macromolecule of pine would polymerize faster in the adult stage (14, 35 years). The panorama generated from the structural and chemical features of pine native lignin not only benefited to understand the biosynthetic pathways and lignin macromolecules structural variation in plant cell walls from different growth stages but also contributed to the valorization and deconstruction of biomass., (Copyright © 2022. Published by Elsevier B.V.)

Background: Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift., Methods: To investigate the astrocytic activity-driven neuronal synaptic events and behavioral consequences, we chemogenetically activated astrocytes in the DMS using GFAP promoter-driven expression of hM3Dq, the excitatory DREADDs (designer receptors exclusively activated by designer drugs). First, we confirmed the chemogenetically induced cellular activity in the DMS astrocytes using calcium imaging. Then, we recorded electrophysiological changes in the synaptic activity of the two types of medium spiny neurons (MSNs): direct and indirect pathway MSNs. To evaluate the behavioral consequences, we trained mice in nose-poking operant chambers that developed either habitual or goal-directed reward-seeking behaviors., Results: The activation of DMS astrocytes reduced the frequency of spontaneous excitatory postsynaptic currents in the direct pathway MSNs, whereas it increased the amplitude of the spontaneous excitatory postsynaptic currents and decreased the frequency of spontaneous inhibitory postsynaptic currents in the indirect pathway MSNs. Interestingly, astrocyte-induced DMS neuronal activities are regulated by adenosine metabolism, receptor signaling, and transport. Importantly, mice lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1), show no transition from habitual to goal-directed reward-seeking behaviors upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition., Conclusions: Our findings reveal that DMS astrocyte activation differentially regulates MSNs' activity and facilitates shifting from habitual to goal-directed reward-seeking behavior., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Hand hygiene (HH) is crucial to prevent healthcare-associated infections and the spread of multidrug-resistant organisms. The monitoring of HH compliance may be affected by observer expertise. A sufficient duration of HH is necessary to remove microorganisms. The aim of this study was to measure compliance with both the World Health Organization (WHO) checklist and optimal HH as reported by unit-based observers and infection control nurses (ICN)., Methods: Optimal HH was defined as adhering to the exact duration and following a six-step procedure. The disparity in compliance with the WHO checklist and optimal HH was analyzed among each profession, unit, and indication, covering a period of 3 years., Results: There was a statistically significant difference in WHO checklist compliance (94.4% vs. 87.0%, p<0.01) and optimal HH rate (86.3% vs. 42.4%, p<0.01) between unit-based observers and ICN. The optimal HH rate was especially lower for doctors (30.1%), in the intensive care units (39.4%), and before clean and aseptic procedures (37.0%) as observed by ICN., Conclusions: Although the overall WHO checklist HH rate was reported to be higher than 90%, optimal HH was only half this rate. More education and awareness of the significance of HH, as well as adherence to the optimal HH procedures, are needed to prevent hospital-acquired infections., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the distribution and structural features of lignin in heartwood, sapwood, and bark of terrestrial plants is important to optimize the industrial utilization of lignocellulose. In this work, the lignins in heartwood, sapwood, and bark of Eucalyptus urophylla × E. grandis were comparatively studied. Confocal Raman microscopy was used to probe the heterogeneity of lignin distribution in situ. The swollen residual enzyme lignin samples were isolated and systematically characterized to determine the structural differences. The results showed that the content and molecular weights of lignin gradually decreased in the order of heartwood, sapwood, and bark. The S/G ratios of heartwood lignin (3.45) and sapwood lignin (2.74) suggested the increase of deposited S-type lignin with the maturity of wood. The bark lignin exhibited a high frequency of β-O-4' linkages and showed a unique substructural pattern with the absence of spirodienone substructures and p-hydroxycinnamyl alcohol end-groups., (Copyright © 2018. Published by Elsevier B.V.)

A facile inorganic complex synthesis route has been developed to synthesis V2O5 nanostructures. The effects of varying incubation time on the crystallinity and morphology of the V2O5 phase has been investigated. The obtained XRD result clearly revealed the pure orthorhombic V2O5 crystalline phase. Raman antiphase bridging VO and chaining VO stretching modes peaks at 686 and 521cm(-1) attributed orthorhombic V2O5 characteristics. The V2p3/2 peak at the binding energies of 517eV and V2p1/2 peak at 524eV assigned to V(5+) oxidation state. Bioinspired V2O5 nanostructures as a biocompatible material for anticancer agents show excellent cytotoxicity at higher V2O5 concentration., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Perfect α-Bi2O3 nanocrystals were successfully synthesized via green synthesis method. X-ray diffraction studies clearly revealed a single phase α-Bi2O3 nanocrystal without any secondary phase. The strong XPS peaks observed at 160 and 165 eV were assigned to Bi4f5/2 and Bi4f7/2 and clearly revealed Bi(3+) valence states of bismuth ions. Photoluminescence spectra revealed the perfect α-Bi2O3 crystal nature without having inter band transitions between defects, impurity and different valence states of bismuth ions. Out of thirty expected modes, the symmetry assignments of Raman bands correlated to Bg(4), Ag(5), Bg(5), Bg(6), Ag(7), Ag(8), Ag(9), Ag(10), Ag(12) and Ag(14) modes revealed perfect α-Bi2O3 nanocrystals. Transmission electron microscopy studies combined with a selected area electron diffraction pattern recorded on α-Bi2O3 nanocrystals show monoclinic structure preferential orientation with sizes approximately 200 nm in diameters and 500 nm in length., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A naturally occurring rambutan peel waste was employed to synthesis bioinspired zinc oxide nanochains. Rambutan peels has the ability of ligating zinc ions as a natural ligation agent resulting in zinc oxide nanochains formation due to its extended polyphenolic system over incubation period. Successful formation of zinc oxide nanochains was confirmed employing transmission electron microscopy studies. About 60% and ∼40% cell viability was lost and 50% and 10% morphological change was observed in 7 and 4 days incubated ZnO treated cells compared with control. Moreover, 50% and 55% of cell death was observed at 24 and 48 h incubation with 7 days treated ZnO cells and hence alters and disturbs the growth of cancer cells and could be used for liver cancer cell treatment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Cyclin A1 is an A-type cyclin that directly binds to CDK2 to regulate cell-cycle progression. In the present study, we found that doxorubicin decreased the expression of cyclin A1 at the protein level in A549 lung cancer cells, while markedly downregulating its mRNA levels. Interestingly, doxorubicin upregulated caspase-1 in a concentration-dependent manner, and z-YAVD-fmk, a specific inhibitor of caspase-1, reversed the doxorubicin-induced decrease in cyclin A1 in A549 lung cancer and MCF7 breast cancer cells. Active caspase-1 effectively cleaved cyclin A1 at D165 into two fragments, which in vitro cleavage assays showed were further cleaved by caspase-3. Finally, we found that overexpression of cyclin A1 significantly reduced the cytotoxicity of doxorubicin, and knockdown of cyclin A1 by RNA interference enhanced the sensitivity of cells to ionizing radiation. Our data suggest a new mechanism for the downregulation of cyclin A1 by DNA-damaging stimuli that could be intimately involved in the cell death induced by DNA damage-inducing stimuli, including doxorubicin and ionizing radiation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In the present investigation, we report a sustainable novel green synthetic strategy to synthesis zinc oxide nanocrystals. This is the first report on sustainable biosynthesis of zinc oxide nanocrystals employing Nephelium lappaceum L., peel extract as a natural ligation agent. Green synthesis of zinc oxide nanocrystals was carried out via zinc-ellagate complex formation using rambutan peel wastes. The successful formation of zinc oxide nanocrystals was confirmed employing standard characterisation studies. A possible mechanism for the formation of ZnO nanocrystals with rambutan peel extract was also proposed. The prepared ZnO nanocrystals were coated on the cotton fabric and their antibacterial activity were analyzed. ZnO nanocrystals coated cotton showed good antibacterial activity towards Escherichia coli (E. coli), gram negative bacteria and Staphylococcus aureus (S. aureus), gram positive bacteria., (Copyright © 2014 Elsevier B.V. All rights reserved.)

TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The PI3K/Akt/mTOR axis in lung cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for lung cancer. However, non-small cell lung cancer cells are resistant to BEZ235, a dual inhibitor of PI3K and mTOR. Interestingly, blockage of Stat3 with a selective inhibitor, S3I-201, or siRNA dramatically sensitized the BEZ235-induced cell death, as evident from increased PARP cleavage. Furthermore, inhibition of Stat3 led to enhancement of cell death induced by LY294002, a PI3K inhibitor. Treatment of cells with a combination of BEZ235 and S3I-201 significantly induced the proapoptotic transcription factor, CHOP, and its targets, Bim and DR4. Knockdown of CHOP or Bim suppressed cell death stimulated by the combination treatment, implicating the involvement of these BEZ235/S3I-201-induced factors in pronounced cell death. Moreover, the BEZ235/S3I-201 combination enhanced TRAIL-induced cell death. Our results collectively suggest that blockage of Stat3 presents an effective strategy to overcome resistance to PI3K/Akt/mTOR inhibition., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Our aim was to structure the configuration of family caregivers' management strategies for the person with dementia (PWD) and to examine factors differentiating caregiving styles., Methods: Using a latent class analysis on the data (N = 338) collected from an ambulatory dementia clinic of a tertiary hospital and the local Alzheimer association, we classified overall patterns of caregivers' dementia management strategies into three domains: criticism, encouragement, and active management. As determinants related to caregiving style, caregiver sociodemographics, caregiving experience, and health outcomes were tested while controlling for the PWD's characteristics., Results: A hierarchical structure of dementia caregiving style was classified into three groups: passive class (33.24%), authoritarian class (29.12%), and nurturing class (37.65%). Caregiver's marital status, employment, reaction to PWD's memory and behavior problems, sense of competence, and perceived gains from caregiving were significantly associated with the caregiving styles derived. In particular, the authoritarian class perceived higher burden whereas the nurturing class was associated with greater gains., Conclusion: A better understanding of caregiver coping and caregiving style is critical to improving care for the PWD. Information on predictive factors related to more constructive coping strategies can be beneficial to design interventions for caregivers. Understanding caregiving styles may thus provide meaningful evidence for more efficient allocation of supportive resources to caregivers caring for the PWD., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Resistance of estrogen receptor-positive breast cancer cells to tamoxifen represents a major barrier to the successful treatment of breast cancer. In the present study, we found that vacuolar H+ ATPase (vATPase) inhibitors, bafilomycin A1 and concanamycin A, sensitize tamoxifen-induced cell death. siRNA targeting ATP6V0C, a 16-kDa hydrophobic proteolipid subunit of vATPase that plays a central role in H+ transport, markedly increased cell death induced by tamoxifen. Interestingly, bafilomycin A1 induced up-regulation of DR4/DR5 and CHOP. Knock-down of CHOP by siRNA suppressed the cell death induced by bafilomycin A1 and tamoxifen, suggesting that bafilomycin A1-mediated CHOP activation sensitizes to tamoxifen. In addition, we found that bafilomycin A1 enhances TRAIL-induced cell death in breast cancer cells. Furthermore, we showed that combination of vATPase inhibitors with tamoxifen also effectively induced cell death in HER2- and ERα-overexpressing breast cancer cells. Overall, our results demonstrate that inhibition of vATPase can potentiate the apoptotic effects of tamoxifen through up-regulation of CHOP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Oxethazaine, an over-the-counter (OTC) antacid, is a precursor of phentermine, which is the most abused anorectic by methamphetamine users in Korea. However, no studies have investigated the abuse potential of oxethazaine. Therefore, we examined and compared the consequences of oxethazaine and phentermine treatment on animal models of conditioned place preference (CPP) and self-administration. Furthermore, oxethazaine and its metabolites in rat plasma were monitored using liquid chromatography-tandem mass spectrometry (LC-MS/MS) after oxethazaine administration, and compared with phentermine itself after phentermine administration to clarify the relationship between phentermine production by oxethazaine ingestion and the possible oxethazaine dependence. Oxethazaine metabolites were also determined by LC-MS/MS in rat hair after oxethazaine administration to investigate the possibility of phentermine detection in hair from oxethazaine abusers. In the behavioral experiment, phentermine (3mg/kg) produced CPP in mice while oxethazaine (5, 10, and 15mg/kg) did not. Moreover, phentermine (0.25mg/kg/infusion) was self-administered by rats at 80% of free-feeding weight, whereas oxethazaine was not. In the analytical study, mephentermine and phentermine, both oxethazaine metabolites, were detected below the limit of quantitation or not detected in both plasma and hair from rats that had ingested oxethazaine (10mg/kg, single dose or for 2weeks). On the other hand, phentermine was detected in plasma and hair samples from rats that had ingested phentermine (10mg/kg, single dose or for 2weeks). Consequently, phentermine induced significant rewarding effects, but oxethazaine did not. Presumably, either oxethazaine does not have any abuse potential or oxethazaine metabolism to phentermine does not result in a pharmacologically active level of psychostimulant in the body. Furthermore, phentermine was not a major metabolite in hair obtained from oxethazaine abusers, which should make it possible to differentiate between chronic oxethazaine and phentermine users., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Previously we reported that the 50% EtOH extract of Cinnamomum cassia (C. cassia) possesses anxiolytic-like activity in the mouse elevated plus maze (EPM) test. This activity was blocked by the 5-HT(1A) receptor antagonist, WAY 100635. Therefore, in order to investigate the effect of C. cassia on 5-HT(1A) receptor binding, quantitative autoradiography of 5-HT(1A) receptors was carried out in brains of mice treated acutely and repeatedly with C. cassia. Binding of [(3)H]8-OH-DPAT to the 5-HT(1A) receptor was investigated in the mouse brain. After a single treatment of C. cassia (750 mg/kg, p.o.), [(3)H]8-OH-DPAT binding showed a significant increase in the dorsal raphe nucleus (DRN). After repeated treatment with C. cassia (100mg/kg, once a day for 5 days, p.o.), [(3)H]8-OH-DPAT binding showed no significant change in any brain region. Taken together, the anxiolytic-like effect of the 50% EtOH extract of C. cassia might be mediated by region specific change of 5-HT(1A) receptors in the dorsal raphe nucleus., (Copyright © 2012. Published by Elsevier Inc.)

Introduction: Histone deacetylase inhibitors (HDACIs) induce growth arrest and apoptosis in cancer cells. In addition to their intrinsic anticancer properties, HDACIs modulate cellular responses to ionizing radiation (IR). We examined the molecular mechanism(s) associated with the radiosensitizing effects of HDACIs in human lung cancer cells., Methods: Lung cancer cells were pretreated with the appropriate concentrations of suberoylanilide hydroxamic acid or trichostatin A. After 2 hours, cells were irradiated with various doses of γ-IR, and then we performed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence-activated cell sorting analysis, clonogenic assay, and Western blotting to detect cell viability or apoptosis and changes of specific proteins expression levels., Results: In this study, we showed that HDACIs (including suberoylanilide hydroxamic acid and trichostatin A) and IR synergistically trigger cell death in human non-small cell lung cancer cells. Cell viability and clonogenic survival were markedly decreased in cultures cotreated with HDACIs and IR. Interestingly, p53 acetylation at lysine 382 was significantly increased, and c-myc expression simultaneously down-regulated in cotreated cells. Radiosensitization by HDACIs was inhibited on transfection with small interfering RNA against p53 and c-myc overexpression, supporting the involvement of p53 and c-myc in this process. Furthermore, c-myc down-regulation and apoptotic cell death coinduced by IR and HDACI were suppressed in cells transfected with mutant K382R p53 and C135Y p53 displaying loss of acetylation at lysine 382 and DNA-binding activity, respectively., Conclusions: Our results collectively demonstrate that the degree of radiosensitization by HDACIs is influenced by acetyl p53-mediated c-myc down-regulation.

Redd1 acts as a negative regulator of mTOR in response to various stress conditions, but its specific physiological role is currently unclear. In the present study, we showed that Redd1 inhibits the invasive activity of non-small cell lung cancer (NSCLC) cells. Interestingly, expression of Redd1 was extremely low in H1299 cells displaying high invasiveness, compared with that in H460 cells with lower invasive activity. Overexpression of Redd1 inhibited the invasive activity of H1299 cells, while suppression with specific siRNAs enhanced the invasiveness of H460 cells. Knockdown of the mTOR downstream substrate, S6K, resulted in a decrease in the invasive property of H1299 cells. Our results provide preliminary evidence that Redd1 inhibits the invasive activity of NSCLC cells via suppression of the mTOR downstream pathway., (Copyright © 2011 Elsevier Inc. All rights reserved.)

To observe the role of sarcoplasmic protein (SP) on myofibrillar protein (MP) denaturation under a hydrostatic pressure (HP), MP isolated from bovine muscle was treated with 300 MPa by increasing concentrations of SP (0, 0.8, 1.6, and 3.2 mg/ml) from bovine. SDS-PAGE patterns of soluble proteins in 0.1M NaCl (pH 7.4) indicated that a protein (about 100 kDa) from MP decreased with increasing concentrations of SP and that a 97 kDa protein from SP observed with 0.1 MPa was not observed with 300 MPa. SDS-PAGE patterns of soluble proteins in 0.6 M NaCl (pH 7.4) and Ca-ATPase activity showed that the denaturation of myosin heavy chain (MHC) was accelerated with increasing SP concentrations with the 300 MPa treatment. Thus, the addition of SP enhanced HP-induced denaturation of MHC and of a protein from MP of about 100 kDa., (Copyright © 2010. Published by Elsevier Ltd.)

Various experiments and analysis were conducted in order to manufacture a catalyst that could very efficiently oxidize carbon monoxide at room temperature and also to identify the relevant factors influencing the oxidation reaction. Pt/TiO(2) catalyst can increase the oxidizing capability of CO at low temperature and room temperature by reduction. In FT-IR experiments, the catalyst that displayed excellent activity was capable of efficiently oxidizing CO to CO(2) using atmospheric oxygen. Based on the results of XPS analysis, we found that the reduced catalyst changed the platinum's oxidation value to Pt(+2) and Pt(+0). Through the O(2)-reoxidation experiments, the catalyst, which consisted of non-stoichiometric platinum oxidized species, displayed an excellent ability to accept oxygen. In this study, the Pt/TiO(2) catalyst was able to very efficiently oxidize CO at low temperature and room temperature even with a minute quantity of platinum., (Copyright 2010 Elsevier B.V. All rights reserved.)

Various experiments were conducted to improve durability against SO(2) by impregnating the same amount of vanadium in TiO(2) which had the various physical properties. According to those catalysts, the degree of deactivation by SO(2) had various results, and it was found that the production of unreacted NH(3) in selective catalytic reduction reaction should be low. Based on X-ray photoelectron spectroscopy analysis, O(2) on-off test, O(2) reoxidation test and H(2)-temperature programmed reduction experiment, the redox capacity of catalyst was improved due to increasing of non-stoichiometric compounds. Such a non-stoichiometric oxide and redox capacity of catalyst can be enhanced by the ball-milling process, and the production of ammonium sulfate salt can be more easily inhibited by the superior oxidation-reduction capacity of catalyst. We found that this result is caused by producing and increasing of V(x+) (x

Heat-shock protein 27 (HSP27), a member of the small heat-shock protein family, is a molecule involved in cellular protection in response to a variety of stresses such as heat shock, toxicants, and oxidative stress. HSP27 is also known to modulate cell functions via interaction with the actin cytoskeleton. To elucidate the functions of HSP27 in adhesion and invasion in more detail, we examined NIH3T3 cells overexpressing HSP27. HSP27 overexpression affected FAK phosphorylation and focal adhesion formation, depending on integrin-mediated actin cytoskeleton polymerization. In addition, the HSP27-overexpressing cells showed a retarded cell migration and invasion in wound-healing assays. Such HSP27-mediated retarded wound healing was correlated with reduced matrix metalloproteinase-2 (MMP-2) expression. The transcription factor for MMP-2 expression, signal transducer and activator or transcription 3 (STAT3), was correspondingly less phosphorylated. When a phosphomimetic form of HSP27 was transiently transfected, migration and invasion were similarly decreased via the regulation of the FAK/STAT3/MMP-2 signaling pathway, whereas a non-phosphorylatable form of HSP27 blocked HSP27-mediated phenotypes probably due to a dominant-negative effect on phosphorylation of endogenous HSP27. Altogether, our results suggest that HSP27 can enhance cell adhesion and modulate cell migration and invasion via the coordination of FAK-dependent actin organization and STAT3-dependent MMP-2 expression, and that phosphorylation of HSP27 is indispensable to regulate this signal pathway.

It was recently established that fructose-1,6-bisphosphate (FBP) aldolase (FBA) and tagatose-1,6-bisphosphate (TBP) aldolase (TBA), two class II aldolases, are highly specific for the diastereoselective synthesis of FBP and TBP from glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP), respectively. In this paper, we report on a FBA from the thermophile Thermus caldophilus GK24 (Tca) that produces both FBP and TBP from C(3) substrates. Moreover, the FBP:TBP ratio could be adjusted by manipulating the concentrations of G3P and DHAP. This is the first native FBA known to show dual diastereoselectivity among the FBAs and TBAs characterized thus far. To explain the behavior of this enzyme, the X-ray crystal structure of the Tca FBA in complex with DHAP was determined at 2.2A resolution. It appears that as a result of alteration of five G3P binding residues, the substrate binding cavity of Tca FBA has a greater volume than those in the Escherichia coli FBA-phosphoglycolohydroxamate (PGH) and TBA-PGH complexes. We suggest that this steric difference underlies the difference in the diastereoselectivities of these class II aldolases.

A recombinant thermophilic Thermus caldophilus GK24 hexokinase, one of the ROK-type (repressor protein, open reading frames, and sugar kinase) proteins, exists uniquely as a 120 kDa molecule with four subunits (31 kDa), in contrast to eukaryotic and bacterial sugar kinases which are monomers or dimers. The optimal temperature and pH for the enzyme reaction are 70-80 degrees C and 7.5, respectively. This enzyme shows broad specificity toward glucose, mannose, glucosamine, allose, 2-deoxyglucose, and fructose. To understand the sugar specificity at a structural level, the enzyme-ATP/Mg2+-sugar binding complex models have been constructed. It has been shown that the sugar specificity is probably dependent on the interaction energy occurred by the positional proximity of sugars bound in the active site of the enzyme, which exhibits a tolerance to modification at C2 or C3 of glucose.