Input: The gender-specific alterations of pGR232-Cdk5 signaling and BDNF gene expression in HIPPO and normalization of depressive-like behavior upon FLU treatment distinguishes this signaling pathway as potential future antidepressant target for gender-specific therapy of stress related mood disorders.

FLU


Input: Improved pharmaceutical stability of a boronphenylalanine mannitol formulation for boron neutron capture therapy.

boronphenylalanine mannitol

boron


Input: Boron neutron capture therapy (BNCT) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug.

Boron

boron


Input: These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf-life and clinical acceptability of the current fructose based L-boronphenylalanine (BPA) formulation.

fructose

L-boronphenylalanine

BPA


Input: Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated.

mannitol BPA


Input: A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures.

mannitol BPA


Input: After suitable periods the formulation was analysed by HPLC for BPA and degradation products.

BPA


Input: Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products.

mannitol BPA

BPA


Input: Autoclaving the solution induced and accelerated degradation.


Input: A solution or lyophilised mannitol BPA formulation has a shelf-life of between 1 and 4 years respectively, a marked improvement over the current fructose formulation.

mannitol BPA

fructose


Input: Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving.


Input: The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT.

mannitol

BPA


Input: Methods for analysis of citrinin in human blood and urine.

citrinin


Input: Citrinin (CIT), produced by several Penicillium, Aspergillus, and Monascus species, has been detected as contaminant in feeds, grains, and other food commodities.

Citrinin

CIT


Input: CIT can co-occur with ochratoxin A (OTA), a mycotoxin also known for its nephrotoxicity, and this raises concern regarding possible combined effects.

CIT

ochratoxin A

OTA


Input: But, in contrast to OTA, data on CIT contamination in foods for human consumption are scarce, and CIT biomonitoring has not been conducted so far due a lack of suitable methods for human specimen.

OTA

CIT

CIT


Input: Thus, it was the aim of the present study to develop sensitive methods for the analysis of CIT in human blood and urine to investigate human exposure.

CIT


Input: To this end, we assessed different methods of sample preparation and instrumental analysis for these matrices.


Input: Clean-up of blood plasma by protein precipitation followed by LC-MS/MS-based analysis allowed robust detection of CIT (LOD 0. 07 ng/mL, LOQ 0. 15 ng/mL).

CIT


Input: For urine, sample clean-up by an immunoaffinity column (CitriTest ((R))) proved to be clearly superior to SPE with RP (18) material for subsequent analysis by LC-MS/MS.


Input: For CIT and its metabolite dihydrocitrinone (HO-CIT), the LOD and LOQ determined by external calibration curves in matrix were 0. 02 and 0. 05 ng/mL for CIT, and those for HO-CIT were 0. 05 and 0. 1 ng/mL urine.

CIT

dihydrocitrinone

HO-CIT

CIT

HO-CIT


Input: The newly developed method was applied in a small pilot study: CIT was present in all plasma samples from 8 German adults, at concentrations ranging from 0. 11 to 0. 26 ng/mL.

CIT


Input: The molar (nM) concentrations of CIT are similar to those measured for OTA in these samples as a result of dietary mycotoxin intake.

CIT

OTA


Input: CIT was detected in 8/10 urines (from 4 adults and 6 infants) in a range of 0. 16-0. 79 ng/mL, and HO-CIT was present in 5/10 samples at similar concentrations.

CIT

HO-CIT


Input: Thus, CIT is excreted in urine as parent compound and also as metabolite.

CIT


Input: These first results in humans point to the need for further studies on CIT exposure.

CIT


Input: Bioactive microconstituents and antioxidant properties of wild edible mushrooms from the island of Lesvos, Greece.


Input: Crude composition, fatty acids, sterols, total phenolic content (TPC), individual polyphenols and terpenic acids were determined in five wild edible mushrooms species (Lactarius deliciosus, Lactarius sanguifluus, Lactarius semisanguifluus, Russula delica, Suillus bellinii) from Lesvos Island, Greece.

fatty acids

sterols

polyphenols

terpenic acids


Input: In addition, the DPPH scavenging capacity, the ferric ion reducing power (FRAP) and the ferrous ion chelating activity of mushroom methanolic extracts were assessed.

DPPH

ferric

ferrous


Input: Among sterols, ergosterol predominated at concentrations 9. 2-18. 0mg/100g fw.

sterols

ergosterol


Input: Total phenolic content of mushroom extracts ranged from 6. 0 to 20. 8mg GAE/100g fw.


Input: Up to 19 simple polyphenols were determined in mushrooms extracts, the more abundant being p-OH-benzoic acid, p-OH-phenylacetic acid, o-coumaric acid, ferulic acid and chrysin.

polyphenols

p-OH-benzoic acid

p-OH-phenylacetic acid

o-coumaric acid

ferulic acid

chrysin


Input: In addition, the triterpenic acids oleanolic and ursolic were detected for the first time in mushrooms.

triterpenic acids oleanolic

ursolic


Input: All species exerted antioxidant activity and ferrous ion chelating capacity.

ferrous


Input: Principal component analysis revealed good correlations between TPC, DPPH and FRAP but not with metal chelating activity.

DPPH


Input: It seems that mushrooms polyphenols exert antiradical and reducing activities, but they are not strong metal chelators, the observed chelating ability being probably due to other classes of compounds.

polyphenols


Input: To our knowledge, this is the first report on the bioactive microconstituents and antioxidant activity of wild Greek edible mushrooms.


Input: Subchronic memantine induced concurrent functional disconnectivity and altered ultra-structural tissue integrity in the rodent brain: revealed by multimodal MRI.

memantine


Input: BACKGROUND: An effective NMDA antagonist imaging model may find key utility in advancing schizophrenia drug discovery research.

NMDA


Input: We investigated effects of subchronic treatment with the NMDA antagonist memantine by using behavioural observation and multimodal MRI.

NMDA

memantine


Input: METHODS: Pharmacological MRI (phMRI) was used to map the neuroanatomical binding sites of memantine after acute and subchronic treatment.

memantine


Input: Resting state fMRI (rs-fMRI) and diffusion MRI were used to study the changes in functional connectivity (FC) and ultra-structural tissue integrity before and after subchronic memantine treatment.

memantine


Input: Further corroborating behavioural evidences were documented.


Input: RESULTS: Dose-dependent phMRI activation was observed in the prelimbic cortex following acute doses of memantine.

memantine


Input: Subchronic treatment revealed significant effects in the hippocampus, cingulate, prelimbic and retrosplenial cortices.


Input: Decreases in FC amongst the hippocampal and frontal cortical structures (prelimbic, cingulate) were apparent through rs-fMRI investigation, indicating a loss of connectivity.


Input: Diffusion kurtosis MRI showed decreases in fractional anisotropy and mean diffusivity changes, suggesting ultra-structural changes in the hippocampus and cingulate cortex.


Input: Limited behavioural assessment suggested that memantine induced behavioural effects comparable to other NMDA antagonists as measured by locomotor hyperactivity and that the effects could be reversed by antipsychotic drugs.

memantine

NMDA


Input: CONCLUSION: Our findings substantiate the hypothesis that repeated NMDA receptor blockade with nonspecific, noncompetitive NMDA antagonists may lead to functional and ultra-structural alterations, particularly in the hippocampus and cingulate cortex.

NMDA

NMDA


Input: These changes may underlie the behavioural effects.


Input: Furthermore, the present findings underscore the utility and the translational potential of multimodal MR imaging and acute/subchronic memantine model in the search for novel disease-modifying treatments for schizophrenia.

memantine


Input: A prospective study of selenium concentration and risk of preeclampsia in pregnant Iranian women: a nested case-control study.

selenium


Input: Preeclampsia remains a leading cause of maternal and perinatal mortality and morbidity worldwide; however, its specific etiology still remains obscure.


Input: Some studies implicate poor maternal selenium status predisposing the mother to preeclampsia.

selenium


Input: This study was designed to determine changes in plasma selenium levels in women having preeclampsia as compared with those with normal pregnancy.

selenium


Input: In a nested case-control study, 650 normal primigravida in their first 24-28 weeks participated in the study.


Input: After 3 months of follow-up of all subjects, blood selenium levels were measured in 38 women presenting consecutively with preeclampsia and in 38 women having a normal pregnancy by atomic absorption spectrophotometry.

selenium


Input: Birth outcomes were recorded, such as gestational age at delivery, height, weight, birth head circumflex and 1-min Apgar score.


Input: Preeclampsia affects about 5. 84% of pregnancies, and in our study, there were no significant differences in age, anthropometric indices, and family history of preeclampsia between the preeclamptic and control groups.


Input: The selenium concentrations in plasma in women with preeclampsia were significantly lower as compared with those in women with normal pregnancy (70. 63 +/- 21. 41 versus 82. 03 +/- 15. 54 mu g/L, p < 0. 05).

selenium


Input: Being in the bottom tertile of selenium concentration (less than 62. 2 mu g/L) was associated with greater risk of preeclampsia in pregnant women.

selenium


Input: The reduced selenium in the maternal circulations observed in the preeclamptic mothers support the hypothesis that insufficient selenium concentration may be a contributing factor to the pathophysiological mechanisms associated with preeclampsia, and optimizing the dietary selenium intake through supplementation could produce demonstrable clinical benefits.

selenium

selenium

selenium


Input: Environmental concentrations and bioaccumulations of cadmium and zinc in coastal watersheds along the Chinese Northern Bohai and Yellow Seas.

cadmium

zinc


Input: Cadmium (Cd) and zinc (Zn) in surface water, sediment, carp, and crab samples collected from upstream and downstream regions of coastal watersheds along the Chinese Northern Bohai and Yellow Seas were analyzed to provide a comprehensive understanding and assessment of their environmental concentrations and bioaccumulations.

Cadmium

Cd

zinc

Zn


Input: The results showed that downstream waters contaminated with Zn would have adverse effects on aquatic organisms.

Zn


Input: Although nearly all sediments were contaminated with Cd due to human activities, little potential existed for Cd toxicity in sediment-dwelling fauna.

Cd

Cd


Input: Concentrations of Cd and Zn in most water, sediment, carp, and crab were less than published values.

Cd

Zn


Input: The downstream carp and crabs had higher mean bioaccumulation factors and biota-sediment accumulation factors for Cd but lower mean biota-sediment accumulation factors for Zn than the upstream carp and crabs.

Cd

Zn


Input: Based on the relationships among Cd and Zn concentrations in water, sediment, and biota, the authors conclude that Cd and Zn in crabs primarily derived from sediment exposure.

Cd

Zn

Cd

Zn


Input: Although Cd and Zn in water and sediment originated from some of the same sources, the sources of Cd or Zn in water were likely different from those in sediment.

Cd

Zn

Cd

Zn


Input: The reversal of inhibitors in congenital hemophilia.


Input: Hemophilias A and B are heritable bleeding disorders characterized by deficient baseline levels of factor VIII (fVIII) and factor IX (fIX), respectively.


Input: Standard treatment for acute bleeding events and for prophylaxis in patients with severe disease consists of recombinant fVIII and fIX infusions.


Input: The development of alloantibodies, or inhibitors, is a serious complication of congenital hemophilia that may impair the effectiveness of fVIII and fIX, leading to increased morbidity and cost of therapy.


Input: When inhibitors are present, bypassing agents such as recombinant activated factor VII and factor eight inhibitor bypass agent are available for treatment of bleeding events.


Input: Although usually effective, they are costly treatments.


Input: Immune-modulatory therapy may reverse inhibitors, allowing fVIII and fIX to be used again.


Input: Immune tolerance induction is the chief treatment option to decrease inhibitor levels, but about 20-30% of patients fail this treatment.


Input: Alternatively, multiple immune-modulating agents have been tried with limited success.


Input: Rituximab, an anti-CD20 monoclonal antibody, is one therapy that has been successful in reducing inhibitor titers in multiple case reports.


Input: Although current evidence is limited and questions regarding its use and place in therapy still exist, this agent shows promise for the future.


Input: 3-Methylglutaconic aciduria-lessons from 50 genes and 977 patients.


Input: Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder.

3-methylglutaconic acid


Input: In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation.

leucine


Input: In all other disorders with 3-methylglutaconic aciduria the origin is unknown, yet mitochondrial dysfunction is thought to be the common denominator.


Input: We investigate the biochemical, clinical and genetic data of 388 patients referred to our centre under suspicion of a metabolic disorder showing 3-methylglutaconic aciduria in routine metabolic screening.


Input: Furthermore, we investigate 591 patients with 50 different, genetically proven, mitochondrial disorders for the presence of 3-methylglutaconic aciduria.


Input: Three percent of all urine samples of the patients referred showed 3-methylglutaconic aciduria, often in correlation with disorders not reported earlier in association with 3-methylglutaconic aciduria (e. g. organic acidurias, urea cycle disorders, haematological and neuromuscular disorders).

urea


Input: In the patient cohort with genetically proven mitochondrial disorders 11% presented 3-methylglutaconic aciduria.


Input: It was more frequently seen in ATPase related disorders, with mitochondrial DNA depletion or deletion, but not in patients with single respiratory chain complex deficiencies.


Input: Besides, it was a consistent feature of patients with mutations in TAZ, SERAC1, OPA3, DNAJC19 and TMEM70 accounting for mitochondrial membrane related pathology.


Input: 3-methylglutaconic aciduria is found quite frequently in patients suspected of a metabolic disorder, and mitochondrial dysfunction is indeed a common denominator.


Input: It is only a discriminative feature of patients with mutations in AUH, TAZ, SERAC1, OPA3, DNAJC19 TMEM70.


Input: These conditions should therefore be referred to as inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.


Input: Gas Dielectric Transistor of CuPc Single Crystalline Nanowire for SO2 Detection Down to Sub-ppm Levels at Room Temperature.

CuPc


Input: A room-temperature highly-sensitive SO2 sensor with fast response and complete recovery is constructed based on gas dielectric field-effect transistor (FET) of CuPc single crystalline nanowire.

CuPc


Input: The exposed conductive channel by gas dielectric is responsible for the high sensitivity to SO2 and the adsorption of the SO2 molecules dramatically enhances the field-effect mobility.


Input: These results not only open up new opportunities to develop new SO2 sensors, but also provide an efficient way to improve the performance of organic FETs.


Input: Efficient stacking on protein amide fragments.

amide


Input: The less polar pi-surface of protein amide groups is exposed in many receptor binding sites, either as part of the backbone or in Gln/Asn side chains.

amide

Gln

Asn


Input: Using quantum chemical calculations and Protein Data Bank (PDB) searches on model systems, we investigate the energetics and geometric preferences for the stacking on amide groups of a large number of heteroarenes that are relevant to medicinal chemistry.

amide

heteroarenes


Input: From this study, we discern that the stacking energy of an aromatic ligand substituent can be improved by: 1) orienting the fragment dipole vector such that it is aligned in an antiparallel fashion with the dipole of the interacting protein amide group, 2) increasing its dipole moment, and 3) decreasing its pi-electron density.

amide


Input: These guidelines should be helpful to more rationally exploit this interaction type in future structure-based drug design.


Input: Relation between respiratory function tests and life habits of the university students.


Input: Among the university students especially in adolescence period, smoking habits and unhealthy lifestyles are major problems in social life.


Input: In this study, it is intended to reveal smoking habits and lifestyles of the students from Suleyman Demirel University and to determine the effects of smoking and lifestyles on pulmonary functions.


Input: Materials and methods: Participants were 94 university students who were getting formal education in the Suleyman Demirel University central campus.


Input: Data were analysed by analysis of variance and chi-square tests.


Input: For all analysis, p value of < 0. 05 was considered significant.


Input: Results: Students' mean age was 19. 9 +/- 0. 9 years, and of all the students 74 (78. 7%) were undergraduate students; remaining 20 (21. 3%) were graduate students.


Input: Of all the students, 27 (28. 7%), which comprised the largest group of the students, were living in state dormitory.


Input: Body mass index (BMI) was examined for the study group; according to BMI, body weight was generally within normal limits but 17. 39% of girls' were found to be underweight.


Input: Conclusions: Respiratory parameters can be affected by many factors.


Input: Smoking habit of university students can be prevented, and it is an important point that they have a healthy lifestyle both for their own health and for future generations.


Input: Lapatinib-mediated cyclooxygenase-2 expression via epidermal growth factor receptor/HuR interaction enhances the aggressiveness of triple-negative breast cancer cells.

Lapatinib


Input: Lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) kinase inhibitor, showed clinical benefits in advanced HER2-positive breast cancer patients.

Lapatinib


Input: Because some triple-negative breast cancers (TNBCs) frequently overexpress EGFR, the antitumor activity of lapatinib in such diseases was also tested.

lapatinib


Input: However, the results showed a worse event-free survival rate.


Input: It remains unknown whether and how lapatinib elicits the aggressiveness of such cancer cells.

lapatinib


Input: In this study, our results demonstrated that lapatinib facilitated axillary and lung metastases of triple-negative MDA-MB-231 breast cancer cells without affecting their viability, leading to worse survival in orthotopic xenograft mice.

lapatinib


Input: The lapatinib-increased motility was attributed by the elevation of EGFR through the downregulation of microRNA-7 and by the subsequent overexpression of cyclooxygenase-2 (COX-2).

lapatinib


Input: Strikingly, independent of its kinase activity, the elevated EGFR at least partly stabilized COX-2 expression by enhancing the binding of HuR to COX-2 mRNA.


Input: Our results suggest that lapatinib may increase the migration and invasion of MDA-MB-231 cells by upregulating EGFR and COX-2 through the downregulation of microRNA-7, providing a potential explanation for the worse clinical outcome of TNBC patients who receive lapatinib-based treatment.

lapatinib

lapatinib


Input: These findings also shed new light on the molecular mechanism of COX-2 mRNA stabilization by EGFR in a kinase-independent manner.


Input: Dispersion and Filtration of Carbon Nanotubes (CNTs) and Measurement of Nanoparticle Agglomerates in Diesel Exhaust.

Carbon


Input: Carbon nanotubes (CNTs) tend to form bundles due to their geometry and van der Walls forces, which usually complicates studies of the CNT properties.

Carbon


Input: Dispersion plays a significant role in CNT studies and we summarize dispersion techniques to generate airborne CNTs from suspensions or powders.


Input: We describe in detail our technique of CNT aerosolization with controlled degree of agglomeration using an electrospray system.


Input: The results of animal inhalation studies using the electrosprayed CNTs are presented.


Input: We have performed filtration experiments for CNTs through a screen filter.


Input: A numerical model has been established to simulate the CNT filtration experiments.


Input: Both the modeling and experimental results show that the CNT penetration is less than the penetration for a sphere with the same mobility diameter, which is mainly due to the larger interception length of the CNTs.


Input: There is a need for instruments capable of fast and online measurement of gas-borne nanoparticle agglomerates.


Input: We developed an instrument Universal NanoParticle Analyzer (UNPA) and the measurement results for diesel exhaust particulates are presented.


Input: The results presented here are pertinent to non-spherical aerosol particles, and illustrate the effects of particle morphology on aerosol behaviors.


Input: Design and synthesis of cyclopropylamide analogues of combretastatin-A4 as novel microtubule-stabilizing agents.

cyclopropylamide


Input: A series of novel cyclopropylamide analogues of combretastatin-A4 (CA-4) were designed and synthesized.

cyclopropylamide


Input: Most of them had significant in vitro antiproliferative activities, particularly for compounds 7i4, 7c4, 8a4, and 8c4.


Input: Moreover, compound 8c4 was also equally potent against paclitaxel resistant cancer cells.

paclitaxel


Input: Interestingly, the novel cyclopropylamide analogues had different binding mechanisms from CA-4.

cyclopropylamide


Input: Instead of inhibiting tubulin polymerization, these CA-4 derivatives were able to stimulate tubulin polymerization.


Input: Flow cytometry revealed that compound 8c4 arrested A549 cancer cells in the G2/M phase and resulted in cellular apoptosis.


Input: Further immunofluorescence assays revealed that compound 8c4 induced mitotic arrest in A549 cells through disrupting microtubule dynamics.


Input: In addition, compound 8c4 also effectively inhibited the tumor growth in the A549 xenograft model without causing significant loss of body weight.


Input: Compound 8c4 represents a novel class of microtubule-stabilizing agent and can be used as a promising lead for the development of new antitumor agents.


Input: A new iridoid glycoside and potential MRB inhibitory activity of isolated compounds from the rhizomes of Cyperus rotundus L.

iridoid glycoside


Input: A new iridoid glycoside, rotunduside (1), along with four known iridoid glycosides, 10-O-p-hydroxybenzoyltheviridoside (2), 10-O-vanilloyltheviridoside (3), 6''-O-(trans-p-coumaroyl)-procumbide (4) and loganic acid (5), was isolated from the rhizomes of Cyperus rotundus L.

iridoid glycoside

rotunduside

iridoid glycosides

loganic acid


Input: Their chemical structures were elucidated on the basis of UV, IR, MS and NMR spectroscopic analyses.


Input: In addition, the macrophages respiratory burst (MRB) inhibitory activity of the isolated compounds was reported.


Input: Compound 2 exhibited considerable MRB inhibitory activity in the test with IC (50) value of ~ 37 mu M.


Input: Two new glycosides from Vitex negundo.


Input: Two new glycosides, 2-methyl pyromeconic acid 3-O-beta-d-glucopyranoside-6'-(O-4''-hydroxybenzoate) (1), 6'-O-p-hydroxybenzoyl-gardoside (2) and four known iridoid glycosides (3-6) were isolated from the whole plant of Vitex negundo.

2-methyl pyromeconic acid 3-O-beta-d-glucopyranoside-6'-(O-4''-hydroxybenzoate)

iridoid glycosides


Input: Their structures were elucidated on the basis of spectroscopic methods including HR-ESI-MS, 1D and 2D NMR.


Input: Identification of alpha-tocopherol and alpha-tocopheryl acetate from the cuticle of soybean pods armyworm (Spodoptera cosmioides).

alpha-tocopherol

alpha-tocopheryl acetate


Input: The chemical composition of the soybean pods armyworm Spodoptera cosmioides (Walker, 1858) (Lepidoptera: Noctuidae) and Anticarsia gemmatalis H u bner, 1818 (Lepidoptera: Erebidae) larval cuticles was evaluated using gas chromatography coupled to a mass detector (GC-MS).


Input: Among the usual lipids found in the insect cuticle, alpha-tocopherol and alpha-tocopheryl acetate were also isolated from S. cosmioides.

alpha-tocopherol

alpha-tocopheryl acetate


Input: On the other hand, no vitamin E derivative was found in A. gemmatalis exuvia.

vitamin E


Input: This is the first report of vitamin E occurrence in the insect' s cuticle.

vitamin E


Input: Bioactives and nutraceutical phytochemicals naturally occurring in virgin olive oil.


Input: The case study of the Nocellara del Belice Italian olive cultivar.


Input: This work reports on the composition and bionutritional value of organic virgin olive oil from the Nocellara del Belice variety, one cultivated in the olive areas of the Sicily region, Italy.


Input: Destoned oils obtained by processing olives with a destoning-based procedure were compared with conventional oils.


Input: This innovative technique, consisting in removing the stone from fruits prior to processing, strongly enhanced the already high-quality level of the conventional product.


Input: An in-depth analytical investigation from 2008 to 2010 showed how this innovative olive extraction process led to an excellent peculiar final product, mainly attributable to the improved biophenol and volatile composition, as well as higher concentrations of the lipophilic and vitamin antioxidants (tocopherols and tocotrienols).

tocopherols

tocotrienols


Input: It had higher levels of oleocanthal (p-HPEA-EDA), a nutraceutical compound exerting actions against COX1 and COX2 (cycloxygenases).

oleocanthal

p-HPEA-EDA


Input: Its head-space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the lipoxygenase (LOX)-pathway (one having as precursors the polyunsaturated fatty acids containing a cis-cis-1, 4-pentadiene system).

polyunsaturated fatty acids

cis-cis-1, 4-pentadiene


Input: Among the other bioactives, we highlight its significant levels of trans-beta-carotene and xanthophylls (lutein, violaxanthin, neoxanthin and other carotenoids).

trans-beta-carotene

xanthophylls

lutein

violaxanthin

neoxanthin


Input: Its enhanced nutritional value was also attributable to the increased intensity of valuable tasting notes.


Input: Revealing the excited-state dynamics of the fluorescent protein Dendra2.


Input: Green-to-red photoconversion is a reaction that occurs in a limited number of fluorescent proteins and that is currently mechanistically debated.


Input: In this contribution, we report on our investigation of the photoconvertible fluorescent protein Dendra2 by employing a combination of pump-probe, up-conversion and single photon timing spectroscopic techniques.


Input: Our findings indicate that upon excitation of the neutral green state an excited state proton transfer proceeds with a time constant of 3. 4 ps between the neutral green and the anionic green states.


Input: In concentrated solution we detected resonance energy transfer (25 ps time constant) between green and red monomers.


Input: The time-resolved emission spectra suggest also the formation of a super-red species, first observed for DsRed (a red fluorescent protein from the corallimorph species Discosoma) and consistent with peculiar structural details present in both proteins.


Input: Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in beta-cyclodextrin.

p-cymene

beta-cyclodextrin


Input: Previously, we have demonstrated the analgesic-like property of p-cymene in rodents.

p-cymene


Input: Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems.

p-cymene

monoterpenes


Input: Here, we used p-cymene/beta-cyclodextrin (beta-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene.

p-cymene

beta-cyclodextrin

beta-CD

p-cymene

monoterpene


Input: Male mice (26-30g) were pretreated with PC/beta-CD (20 or 40mg/kg, p. o.), PC (20 or 40mg/kg, p. o.) or vehicle (distilled water), 0. 5h before painful tests and antinociceptive effect was evaluated at times: 0. 5, 1, 2, 4, 8, and 16h after treatment.

beta-CD


Input: We evaluated the analgesic-like effect of PC/beta-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus.

beta-CD

acetic acid


Input: Our results demonstrated that acute treatment with complex PC/beta-CD produced an antinocicepitve effect (p < 0. 01 or p < 0. 001) for 8h followed whereas isolated PC produced the same effect for 2h.

beta-CD


Input: Similar results were obtained in hot-plate test, PC/beta-CD, in all doses, significantly reduces (p < 0. 01 or p < 0. 001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose.

beta-CD


Input: Such results were unlikely to be caused by motor abnormality.


Input: Systemic pretreatment with PC/beta-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/beta-CD did so during a longer period when compared with isolated monoterpene alone.

beta-CD

beta-CD

monoterpene


Input: Our results provide evidence to propose that the complex with beta-CD improved analgesic and anti-inflammatory effects of p-cymene.

beta-CD

p-cymene


Input: Towards the validation of a lung tumorigenesis model with mainstream cigarette smoke inhalation using the A/J mouse.


Input: A generally accepted and validated laboratory model for smoking-associated pulmonary tumorigenesis would be useful for both basic and applied research applications, such as the development of early diagnostic endpoints or the evaluation of modified risk tobacco products, respectively.


Input: The A/J mouse is susceptible for developing both spontaneous and induced lung adenomas and adenocarcinomas, and increased lung tumor multiplicities were also observed in previous cigarette smoke inhalation studies.


Input: The present study was designed to collect data useful towards the validation of an 18-month mainstream smoke (MS) inhalation model.


Input: Male and female A/J mice were exposed whole-body at three MS concentration levels for 6h/day, and the results were compared to a previous study in the same laboratory and with a similar design.


Input: A linear MS concentration-dependent increase in lung tumorigenesis was observed with similar slopes for both sexes and both studies and a maximal 5-fold increase in multiplicity beyond sham control.


Input: The minimal detectable difference in lung tumor multiplicity for the current study was 37%.


Input: In the larynx, papillomas were detectable in all MS-exposed groups in a non-concentration dependent manner.


Input: No other extra-pulmonary MS-dependent neoplastic lesions were found.


Input: Gene expression signatures of lung tumor tissues allowed a clear differentiation of sham-and high dose MS-exposed mice.


Input: In combination with data from previous smoke inhalation studies with A/J mice, the current data suggest that this model for MS inhalation-induced pulmonary tumorigenesis is reliable and relevant, two crucial requirements towards validation of such a model.


Input: Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells.

Dichloro-dihydro-fluorescein diacetate

DCFH-DA


Input: No consensus exists on how to address possible toxicity of nanomaterials as they interfere with most in vitro screening tests based on colorimetric and fluorimetric probes such as the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay for detection of oxidative species.

dichloro-dihydro-fluorescein diacetate

DCFH-DA


Input: In the present research, nanomaterial interaction with DCFH-DA was studied in relation to its nature and/or assay conditions (cell-based and time exposure) by incubating Rhodamine (Rhd)-labeled 25nm and 50nm silica (SiO2), naked and oleic acid coated magnetite, (Fe3O4) and maghemite (Fe2O3) iron oxide, titanium dioxide (TiO2) and poly (ethylene oxide)-poly (lactide/glycolide) acid (PLGA-PEO) nanoparticles (NPs) with metabolically active rat hepatocytes for 4 and 24-h periods.

DCFH-DA

Rhodamine

Rhd

silica

oleic acid coated magnetite

maghemite

iron oxide

titanium dioxide

poly (ethylene oxide)-poly (lactide/glycolide) acid

PLGA-PEO


Input: Data indicated that nanoparticle uptake correlated with quenching of dye fluorescence emission.


Input: In spite of their masking effect, the oxidative potential of NPs could be detected at a limited threshold concentration when exposed for periods of time longer than those frequently used for this test.


Input: However, changes in the experimental conditions did not systematically result in free radical formation for all nanomaterials tested.


Input: Overall data indicate that despite the quenching effect of nanoparticles on DCFH-DA assay, it can be considered as a useful tool for quantitative measurement of NPs-induced oxidative stress by minor modifications of standardized protocols.

DCFH-DA


Input: Formation of mainstream cigarette smoke constituents prioritized by the World Health Organization--yield patterns observed in market surveys, clustering and inverse correlations.


Input: The WHO TobReg proposed mandating ceilings on selected smoke constituents determined from the market-specific median of nicotine-normalized yield distributions.

nicotine


Input: Data validating this regulatory concept were obtained from essentially single-blend surveys.


Input: This process is strongly impacted by inverse correlations among yields.


Input: In the present study, 18 priority WHO smoke constituent yields (nicotine-normalized) were determined (using two smoking regimens) from 262 commercial brands including American, Virginia and local blends from 13 countries.

nicotine


Input: Principal Component Analysis was used to identify yields patterns, clustering of blend types and the inverse correlations causing these clusters.


Input: Three principal components explain about 75% of total data variability.


Input: PC1 was sensitive to the relative levels of gas-and particle-phase compounds.


Input: PC2 and PC3 cluster American-and Virginia-blends, revealing inverse correlations: Nitrogen oxides and amino-or nitroso-aromatic compounds inversely correlate to either formaldehyde and acrolein, or benzo (a) pyrene and di-hydroxybenzenes.

Nitrogen oxides

amino

nitroso

formaldehyde

acrolein

benzo (a) pyrene

di-hydroxybenzenes


Input: These results can be explained by reviewing the processes determining each components smoke delivery.


Input: Regulatory initiatives simultaneously targeting selected smoke constituents in markets with mixed blend styles will be strongly impacted by the inverse correlations described.


Input: It is difficult to predict the ultimate impact of such regulations on public health, considering the complex chemistry of cigarette smoke formation.


Input: The association between daily calcium intake and sarcopenia in older, non-obese Korean adults: the fourth Korea national health and nutrition examination survey (KNHANES IV) 2009.

calcium


Input: Recent data suggest that variations in calcium intake may influence body weight and composition; however, the relationship between daily calcium intake and muscle mass has not been well established.

calcium

calcium


Input: The objective of this study was to assess the relationship between daily calcium intake and sarcopenia.

calcium


Input: We analyzed data for older adults (over 60 years) from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2009.


Input: A total of 1339 Non-Obese (BMI between 18. 5 and 25 kg/m (2)), older adults (592 men and 707 women) were enrolled.


Input: Dietary variables were assessed using a nutrition survey that used a 24-hour recall method.


Input: Daily calcium intake based on the consumption of each food item was calculated.

calcium


Input: Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight less than 2 SD below the sex-specific mean for young adults.


Input: We found that daily calcium intake was negatively correlated with total body fat percentage and positively correlated with appendicular skeletal mass (p < 0. 001).

calcium


Input: Participants with sarcopenia appear to have significantly lower daily calcium intakes than participants without sarcopenia (p < 0. 001).

calcium


Input: The unadjusted prevalence of sarcopenia according to daily calcium intake tertiles were 6. 3%, 4. 3%, and 2. 7% in tertiles 1, 2, and 3, respectively.

calcium


Input: After adjustment for age, sex, BMI, total energy intake, and lifestyle factors, compared with those in the lowest tertile of daily calcium intake, participants in the highest tertile had an odds ratio for sarcopenia of 0. 295 (95% confidence interval, 0. 087-0. 768; p for trend = 0. 014).

calcium


Input: We found that daily calcium intake, corrected for total energy intake and serum 25 (OH) D status, was significantly lower in subjects with sarcopenia than in those without.

calcium

25 (OH) D


Input: Our results suggest a strong inverse association between daily calcium intake and sarcopenia in non-obese, older Korean adults.

calcium


Input: Functional profiling discovers the dieldrin organochlorinated pesticide affects leucine availability in yeast.

dieldrin

leucine


Input: Exposure to organochlorinated pesticides such as dieldrin has been linked to Parkinson' s and Alzheimer' s diseases, endocrine disruption, and cancer, but the cellular and molecular mechanisms of toxicity behind these effects remain largely unknown.

dieldrin


Input: Here we demonstrate, using a functional genomics approach in the model eukaryote Saccharomyces cerevisiae, that dieldrin alters leucine availability.

dieldrin

leucine


Input: This model is supported by multiple lines of congruent evidence: (1) mutants defective in amino acid signaling or transport are sensitive to dieldrin, which is reversed by the addition of exogenous leucine; (2) dieldrin sensitivity of wild-type or mutant strains is dependent upon leucine concentration in the media; (3) overexpression of proteins that increase intracellular leucine confer resistance to dieldrin; (4) leucine uptake is inhibited in the presence of dieldrin; and (5) dieldrin induces the amino acid starvation response.

amino acid

dieldrin

leucine

dieldrin

leucine

leucine

dieldrin

leucine

dieldrin

dieldrin

amino acid


Input: Additionally, we demonstrate that appropriate negative regulation of the Ras/protein kinase A pathway, along with an intact pyruvate dehydrogenase complex, is required for dieldrin tolerance.

pyruvate

dieldrin


Input: Many yeast genes described in this study have human orthologs that may modulate dieldrin toxicity in humans.

dieldrin


Input: Brain hemispheric differences in the neurochemical effects of lead, prenatal stress, and the combination and their amelioration by behavioral experience.


Input: Brain lateralization, critical to mediation of cognitive functions and to " multitasking, " is disrupted in conditions such as attention deficit disorder and schizophrenia.


Input: Both low-level lead (Pb) exposure and prenatal stress (PS) have been associated with mesocorticolimbic system-mediated executive-function cognitive and attention deficits.

Pb


Input: Mesocorticolimbic systems demonstrate significant laterality.


Input: Thus, altered brain lateralization could play a role in this behavioral toxicity.


Input: This study examined laterality of mesocorticolimbic monoamines (frontal cortex, nucleus accumbens, striatum, midbrain) and amino acids (frontal cortex) in male and female rats subjected to lifetime Pb exposure (0 or 50 ppm in drinking water), PS (restraint stress on gestational days 16-17), or the combination with and without repeated learning behavioral experience.

monoamines

amino acids

Pb


Input: Control males exhibited prominent laterality, particularly in midbrain and also in frontal cortex and striatum; females exhibited less laterality, and this was primarily striatal.


Input: Lateralized Pb +/- PS induced neurotransmitter changes were assessed only in males because of limited sample sizes of Pb + PS females.

Pb

Pb


Input: In males, Pb +/- PS changes occurred in left hemisphere of frontal cortex and right hemisphere of midbrain.

Pb


Input: Behavioral experience modified the laterality of Pb +/- PS-induced neurotransmitter changes in a region-dependent manner.

Pb


Input: Notably, behavioral experience eliminated Pb +/- PS neurotransmitter changes in males.

Pb


Input: These findings underscore the critical need to evaluate both sexes and brain hemispheres for the mechanistic understanding of sex-dependent differences in neuro-and behavioral toxicity.


Input: Furthermore, assessment of central nervous system mechanisms in the absence of behavioral experience, shown here for males, may constitute less relevant models of human health effects.


Input: Transcriptome alterations following developmental atrazine exposure in zebrafish are associated with disruption of neuroendocrine and reproductive system function, cell cycle, and carcinogenesis.

atrazine


Input: Atrazine, a herbicide commonly applied to agricultural areas and a common contaminant of potable water supplies, is implicated as an endocrine-disrupting chemical (EDC) and potential carcinogen.

Atrazine


Input: Studies show that EDCs can cause irreversible changes in tissue formation, decreased reproductive potential, obesity, and cancer.


Input: The U. S.


Input: Environmental Protection Agency considers an atrazine concentration of <= 3 ppb in drinking water safe for consumption.

atrazine


Input: The specific adverse human health effects associated with a developmental atrazine exposure and the underlying genetic mechanisms of these effects are not well defined.

atrazine


Input: In this study, zebrafish embryos were exposed to a range of atrazine concentrations to establish toxicity.

atrazine


Input: Morphological, transcriptomic, and protein alterations were then assessed at 72h postfertilization following developmental atrazine exposure at 0, 0. 3, 3, or 30 ppb.

atrazine


Input: A significant increase in head length was observed in all three atrazine treatments.

atrazine


Input: Transcriptomic profiles revealed 21, 62, and 64 genes with altered expression in the 0. 3, 3, and 30 ppb atrazine treatments, respectively.

atrazine


Input: Altered genes were associated with neuroendocrine and reproductive system development, function, and disease; cell cycle control; and carcinogenesis.


Input: There was a significant overlap (42 genes) between the 3 and 30 ppb differentially expressed gene lists, with two of these genes (CYP17A1 and SAMHD1) present in all three atrazine treatments.

atrazine


Input: Increased transcript levels were translated to significant upregulation in protein expression.


Input: Overall, this study identifies genetic and molecular targets altered in response to a developmental atrazine exposure to further define the biological pathways and mechanisms of toxicity.

atrazine


Input: Integrative Analysis of miRNA and inflammatory gene expression after acute particulate matter exposure.


Input: MicroRNAs (miRNAs) are environmentally sensitive inhibitors of gene expression that may mediate the effects of metal-rich particulate matter (PM) and toxic metals on human individuals.


Input: Previous environmental miRNA studies have investigated a limited number of candidate miRNAs and have not yet evaluated the functional effects on gene expression.


Input: In this study, we wanted to identify PM-sensitive miRNAs using microarray profiling on matched baseline and postexposure RNA from foundry workers with well-characterized exposure to metal-rich PM and to characterize miRNA relations with expression of candidate inflammatory genes.


Input: We applied microarray analysis of 847 human miRNAs and real-time PCR analysis of 18 candidate inflammatory genes on matched blood samples collected from foundry workers at baseline and after 3 days of work (postexposure).


Input: We identified differentially expressed miRNAs (fold change [FC] > 2 and p < 0. 05) and correlated their expression with the inflammatory associated genes.


Input: We performed in silico network analysis in MetaCore v6. 9 to characterize the biological pathways connecting miRNA-mRNA pairs.


Input: Microarray analysis identified four miRNAs that were differentially expressed in postexposure compared with baseline samples, including miR-421 (FC = 2. 81, p < 0. 001), miR-146a (FC = 2. 62, p = 0. 007), miR-29a (FC = 2. 91, p < 0. 001), and let-7g (FC = 2. 73, p = 0. 019).


Input: Using false discovery date adjustment for multiple comparisons, we found 11 miRNA-mRNA correlated pairs involving the 4 differentially expressed miRNAs and candidate inflammatory genes.


Input: In silico network analysis with MetaCore database identified biological interactions for all the 11 miRNA-mRNA pairs, which ranged from direct mRNA targeting to complex interactions with multiple intermediates.


Input: Acute PM exposure may affect gene regulation through PM-responsive miRNAs that directly or indirectly control inflammatory gene expression.


Input: Molecular mechanisms of central leptin resistance in obesity.


Input: The rapidly increasing prevalence of obesity confers a huge health burden globally.


Input: The hypothalamus plays a central role in the regulation of energy homeostasis by integrating multiple metabolic signals from peripheral organs and modulating feeding behavior and energy metabolism.


Input: Leptin, a key appetite-regulating hormone derived from the white adipose tissue, primarily acts on hypothalamic neurons to activate catabolic pathway and inhibit anabolic pathway, which can result in anorexia and weight reduction.


Input: Despite striking obesity resulting from leptin deficiency, treatment with this hormone in human obesity has been unsuccessful due to leptin resistance.


Input: In this review, we describe recent researches extending our understanding of obesity-associated hypothalamic leptin resistance.


Input: Evaluation of Current Eligibility Criteria for Bariatric Surgery: Diabetes prevention and risk factor changes in the Swedish Obese Subjects (SOS) study.


Input: OBJECTIVE Patients with a BMI < 35 kg/m (2) and patients with a BMI between 35 and 40 kg/m (2) without comorbidities are noneligible by current eligibility criteria for bariatric surgery.


Input: We used Swedish obese subjects (SOS) to explore long-term outcomes in noneligible versus eligible patients.


Input: RESEARCH DESIGN AND METHODS The SOS study involved 2, 010 obese patients who underwent bariatric surgery (68% vertical-banded gastroplasty, 19% banding, and 13% gastric bypass) and 2, 037 contemporaneously matched obese controls receiving usual care.


Input: At inclusion, the participant age was 37-60 years and BMI was >= 34 kg/m (2) in men and >= 38 kg/m (2) in women.


Input: The effect of surgery was assessed in patients that do (n = 3, 814) and do not (n = 233) meet current eligibility criteria.


Input: The date of analysis was 1 January 2012.


Input: The follow-up time was up to 20 years, with a median of 10 years.


Input: RESULTS Cardiovascular risk factors were significantly improved both in noneligible and eligible individuals after 10 years of follow-up.


Input: Surgery reduced the diabetes incidence in both the noneligible (adjusted hazard ratio 0. 33 [95% CI 0. 13-0. 82], P = 0. 017) and eligible (0. 27 [0. 22-0. 33], P < 0. 001) groups.


Input: We could not detect a difference in the effect of surgery between the groups (adjusted interaction P value = 0. 713).


Input: CONCLUSIONS Bariatric surgery drastically reduced the incidence of type 2 diabetes both in noneligible and eligible patients and improved cardiovascular risk factors in both groups.


Input: Our results show that strict BMI cutoffs are of limited use for bariatric surgery prioritization if the aim is to prevent diabetes and improve cardiovascular risk factors.


Input: GLP-1 Action and Glucose Tolerance in Subjects With Remission of Type 2 Diabetes Mellitus After Gastric Bypass Surgery.

Glucose


Input: OBJECTIVEGlucagon like peptide-1 (GLP-1) has been suggested as a major factor for the improved glucose tolerance ensuing after Roux-en-Y Gastric Bypass (RYGBP) surgery.

glucose


Input: We examined the effect of blocking endogenous GLP-1 action on glucose tolerance in subjects with sustained remission of type 2 diabetes (T2DM) present before RYGBP. RESEARCH DESIGN AND METHODSBlood glucose, insulin, C-peptide, glucagon, GLP-1, and glucose-dependent insulinotropic peptide levels were measured after a meal challenge with either exendin-(9-39) (a GLP-1r antagonist) or saline infusion in eight subjects with sustained remission of T2DM after RYGBP and seven healthy controls. RESULTSInfusion of exendin-(9-39) resulted in marginal deterioration of the 2-h plasma glucose after meal intake in RYGBP subjects (saline 78. 4 +/- 15. 1 mg/dL compared with exendin-(9-39) 116. 5 +/- 22. 3 mg/dL; P < 0. 001).

glucose

glucose

glucose

glucose


Input: Furthermore, glucose response to meal intake was similarly enlarged in the two study groups (percent change in the area under the curve of glucose exendin-(9-39)-infusion versus saline-infusion: controls 10. 84 +/- 8. 8% versus RYGBP 9. 94 +/- 8. 4%; P = 0. 884).

glucose

glucose


Input: In the RYGBP group, the blockade of the enlarged GLP-1 response to meal intake resulted in reduced insulin (P = 0. 001) and C-peptide (P < 0. 001), but no change in glucagon (P = 0. 258) responses. CONCLUSIONThe limited deterioration of glucose tolerance on blockade of GLP-1 action in our study suggests the resolution of T2DM after RYGBP may be explained by mechanisms beyond enhancement of GLP-1 action.

glucose


Input: Case study of the Swiss flora for prior phytochemical and biological investigations.


Input: Estimates in the literature as to what extent the world' s higher plant species have been studied chemically or for bioactivity are contradictory and range from 0. 5% to > 12%.


Input: In this survey, a model to make credible estimates of the extent of their study is proposed and is exemplified by applying it in a case study of plants native to Switzerland.


Input: Using a widely available database (SciFinder Scholar), 454 535 literature references for the 2677 native Swiss plant species were retrieved.


Input: It was determined that 55% of these species have been investigated phytochemically and 28% for biological activity.


Input: The influence of factors such as commonness, growth form, habitat, medicinal use, and reported toxicity on the extent to which different plant groups have been studied is analyzed.


Input: The predictive value of random sampling of subsets of plants is compared to the study of the entire Swiss flora, to show that a credible estimate of the extent of prior studies can be achieved with just 5% of these species.


Input: Bioactive sesterterpenoids from a Korean sponge Monanchora sp.

sesterterpenoids


Input: Chemical investigation of a Korean marine sponge, Monanchora sp., yielded nine new sesterterpenoids (1-9) along with phorbaketals A-C (10-12).

sesterterpenoids

phorbaketals A-C


Input: The planar structures were established on the basis of NMR and MS analysis, and the absolute configurations of 1-9 were defined using the modified Mosher' s method and CD spectroscopic data analysis.


Input: Compounds 1-8, designated as phorbaketals D-K, possess a spiroketal-modified benzopyran moiety such as phorbaketal A, and their structural variations are due to oxidation and/or reduction of the tricyclic core or the side chain.

phorbaketals D-K

spiroketal

benzopyran

phorbaketal A


Input: Compound 9, designated as phorbin A, has a monocyclic structure and is proposed to be a possible biogenetic precursor of the phorbaketals.

phorbin A

phorbaketals


Input: Compounds 1-9 were evaluated for cytotoxicity against four human cancer cell lines (A498, ACHN, MIA-paca, and PANC-1), and a few of them were found to exhibit cytotoxic activity.


Input: Modulation of cytochrome P450 enzymes in response to continuous or intermittent high-fat diet in pigs.


Input: Abstract 1.


Input: To date, no information has been available on the modulation of cytochrome P450 enzymes (CYPs) following the administration of a hyperlipidemic diet in pigs.


Input: We investigated the potential modulation of xenobiotic-metabolizing CYPs in liver, heart and duodenum of pigs subjected to a high-fat/high-cholesterol diet for 2 months continuously (C-HFD) or on alternate weeks (A-HFD).

cholesterol


Input: The administration of the high-fat diet resulted in considerably increased plasma cholesterol levels although the animals were still able to manage the lipid overload efficiently, and no sign of effective tissue inflammation occurred in livers.

cholesterol


Input: Plasma lipid profile and liver histology indicated a better adaptive response of the A-HFD pigs compared to the C-HFD group.


Input: We showed a post-transcriptional induction of hepatic CYP2E1 activity in C-HFD pigs and a transcriptional induction of hepatic CYP3As-especially in the A-HFD group.


Input: No further CYP modulation was observed in either liver or extra-hepatic tissues.


Input: In conclusion, the administration of a high-fat diet in pigs resulted in limited effects on the drug metabolism system.


Input: The better adaptive response of A-HFD pigs compared to C-HFD pigs is a very interesting observation since the intermittent administration of the diet reflects the mode of human behavior more closely.


Input: Therapeutic potential of targeting lipid aldehydes and lipoxidation end-products in the treatment of ocular disease.

aldehydes


Input: Lipoxidation reactions and the subsequent accumulation of advanced lipoxidation end products (ALEs) have been implicated in the pathogenesis of many of the leading causes of visual impairment.


Input: Here, we begin by outlining some of the major lipid aldehydes produced through lipoxidation reactions, the ALEs formed upon their reaction with proteins, and the endogenous aldehyde metabolizing enzymes involved in protecting cells against lipoxidation mediated damage.

aldehydes

aldehyde


Input: Discussions are subsequently focused on the clinical and experimental evidence supporting the contribution of lipid aldehydes and ALEs in the development of ocular diseases.

aldehydes


Input: From these discussions, it is clear that inhibition of lipoxidation reactions and ALE formation could represent a new therapeutic avenue for the treatment of a broad range of ocular disorders.


Input: Current and emerging pharmacological strategies to prevent or neutralize the effects of lipid aldehydes and ALEs are therefore considered, with particular emphasis on the potential of these drugs for treatment of diseases of the eye.

aldehydes


Input: Exploring a new frontier in cancer treatment: targeting the ubiquitin and ubiquitin-like activating enzymes.


Input: The labeling of proteins with small ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers regulates a plethora of activities within the cell, such as protein recycling, cell cycle modifications, and protein translocation.


Input: These processes are often overactive in diseased cells, leading to unregulated cell growth and disease progression.


Input: Therefore, in systems where Ub/Ubl protein labeling is dysregulated, the development of drugs to selectively and potently disrupt Ub/Ubl protein labeling offers a targeted molecular approach for sensitizing these diseased cells.


Input: This Perspective outlines the progress that has been made in the context of inhibitor development for targeting Ub/Ubl pathways.


Input: Parallel nanometric 3D tracking of intracellular gold nanorods using multifocal two-photon microscopy.


Input: We report a novel technique for long-term parallel three dimensional (3D)-tracking of gold nanorods in live cells with nanometer resolution.


Input: Gold nanorods feature a strong plasmon-enhanced two-photon luminescence, can be easily functionalized, and have been shown to be nontoxic.


Input: These properties make gold nanorods very suitable for in vivo two-photon luminescence microscopy.


Input: By rapid multifocal scanning, we combine the advantages of 3D molecular tracking methods using wide-field imaging with the advantages of two-photon microscopy.


Input: Isolated gold nanorods can be localized with a resolution of 4 nm in the xy-plane and 8 nm in the z-direction.


Input: The polarization-dependence of the two-photon luminescence signal can be used to resolve the angular orientation, even when two gold nanorods are separated by less than the diffraction limit.


Input: Individual nanorods in live U2OS cells could be followed in 3 dimensions for over 30 min, with a photon noise limited accuracy, and a time resolution of 50 ms in 2D and 500 ms in 3D.


Input: Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase PI3K alpha.


Input: PI3K alpha has been identified as an oncogene in human tumors.


Input: By use of rational drug design, a targeted covalent inhibitor 3 (CNX-1351) was created that potently and specifically inhibits PI3K alpha.


Input: We demonstrate, using mass spectrometry and X-ray crystallography, that the selective inhibitor covalently modifies PI3K alpha on cysteine 862 (C862), an amino acid unique to the alpha isoform, and that PI3K beta,-gamma, and-delta are not covalently modified.

cysteine

amino acid


Input: 3 is able to potently (EC (50) < 100 nM) and specifically inhibit signaling in PI3K alpha-dependent cancer cell lines, and this leads to a potent antiproliferative effect (GI (50) < 100 nM).


Input: A covalent probe, 8 (CNX-1220), which selectively bonds to PI3K alpha, was used to investigate the duration of occupancy of 3 with PI3K alpha in vivo.


Input: This is the first report of a PI3K alpha-selective inhibitor, and these data demonstrate the biological impact of selectively targeting PI3K alpha.


Input: Synthesis and Structure-Activity Relationships of N-Methyl-5, 6, 7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents.

N-Methyl-5, 6, 7-trimethoxylindoles


Input: Several new series of 5, 6, 7-trimethoxyindole derivatives were synthesized and their structure-activity relationships (SARs) were studied.

5, 6, 7-trimethoxyindole


Input: Some of these compounds exhibited strong antiproliferative activities in the submicromolar range.


Input: N-Methyl-5, 6, 7-trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities, with IC (50) values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells (HUVECs).

N-Methyl-5, 6, 7-trimethoxylindoles


Input: In addition to vascular disrupting activity verified by in vitro assays, compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA-4.

colchicine


Input: The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2/M phase after treatment with 21 and 31.


Input: It was showed that 21 disrupted tumor vasculature by use of in vivo assay.


Input: Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents.


Input: Bisphenol A activates the Nrf1/2-antioxidant response element pathway in HEK 293 cells.

Bisphenol A


Input: Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins for baby bottles, liners of canned food, and many other consumer products.

Bisphenol A

BPA

polycarbonate


Input: Previously, BPA has been shown to reduce the activity of several antioxidant enzymes, which may contribute to oxidative stress.

BPA


Input: However, the underlying mechanism of the BPA-mediated effect upon antioxidant enzyme activity is unknown.

BPA


Input: Antioxidant and phase II metabolizing enzymes protect cells from oxidative stress and are transcriptionally activated by Nrf1 and Nrf2 factors through their cis-regulatory antioxidant response elements (AREs).


Input: In this work, we have assessed the effect of BPA on the Nrf1/2-ARE pathway in cultured human embryonic kidney (HEK) 293 cells.

BPA


Input: Surprisingly, glutathione and reactive oxygen species (ROS) assays revealed that BPA application created a more reduced intracellular environment in cultured HEK 293 cells.

glutathione

oxygen

BPA


Input: Furthermore, BPA increased the transactivation activity of ectopic Nrf1 and Nrf2 and increased the expression of ARE-target genes ho-1 and nqo1 at high (100-200 mu M) BPA concentrations only.

BPA

BPA


Input: Our study suggests that BPA activates the Nrf1/2-ARE pathway at high (> 10 mu M) micromolar concentrations.

BPA


Input: Organoselenium compounds modulate extracellular redox by induction of extracellular cysteine and cell surface thioredoxin reductase.

Organoselenium

cysteine


Input: The effect of selenium compounds on extracellular redox modulating capacity was studied in murine macrophage RAW 264. 7 cells and differentiated human THP-1 monocytes.

selenium


Input: The arylselenium compounds benzeneselenol (PhSeH), dibenzyl diselenide (DBDSe), diphenyl diselenide (DPDSe), and ebselen were capable of inducing extracellular cysteine accumulation via a cystine-and glucose-dependent process.

arylselenium

benzeneselenol

PhSeH

dibenzyl diselenide

DBDSe

diphenyl diselenide

DPDSe

ebselen

cysteine

cystine

glucose


Input: Extracellular cysteine production was dose-dependently inhibited by glutamate, an inhibitor of cystine/glutamate antiporter (Xc (-) transporter), supporting the involvement of Xc (-) transporter for cystine uptake in the above process.

cysteine

glutamate

cystine

glutamate

cystine


Input: These arylselenium compounds also induced cellular thioredoxin reductase (TrxR) expression, particularly at the exofacial surface of cells.

arylselenium


Input: TrxR1 knockdown using small interfering RNA attenuated TrxR increases and cysteine efflux induced in cells by DPDSe.

cysteine

DPDSe


Input: Sodium selenite (Na2SeO3), selenomethionine (SeMet), seleno-l-cystine (SeCySS), and Se-methylselenocysteine (MeSeCys) did not have these effects on macrophages under the same treatment conditions.

Sodium selenite

selenomethionine

SeMet

seleno-l-cystine

SeCySS

Se-methylselenocysteine

MeSeCys


Input: The effects of organoselenium compounds on extracellular redox may contribute to the known, but inadequately understood, biological effects of selenium compounds.

organoselenium

selenium


Input: A nonribosomal peptide synthetase-derived iron (III) complex from the pathogenic fungus Aspergillus fumigatus.

iron (III)


Input: Small molecules (SMs) play central roles as virulence factors of pathogenic fungi and bacteria; however, genomic analyses suggest that the majority of microbial SMs have remained uncharacterized.


Input: Based on microarray analysis followed by comparative metabolomics of overexpression/knockout mutants, we identified a tryptophan-derived iron (III)-complex, hexadehydro-astechrome (HAS), as the major product of the cryptic has nonribosomal peptide synthetase (NRPS) gene cluster in the human pathogen Aspergillus fumigatus.

tryptophan

iron (III)

hexadehydro-astechrome

HAS


Input: Activation of the has cluster created a highly virulent A. fumigatus strain that increased mortality of infected mice.


Input: Comparative metabolomics of different mutant strains allowed to propose a pathway for HAS biosynthesis and further revealed cross-talk with another NRPS pathway producing the anticancer fumitremorgins.

HAS

fumitremorgins


Input: Intracellular drug concentrations.


Input: Many drug targets are intracellular.


Input: To access them, a drug molecule must pass through the cell membrane, a process often facilitated or impeded by transporters.


Input: Once in the cytoplasm, basic molecules may become concentrated in organelles.


Input: To predict the pharmacologic effect accurately, there must be data concerning the concentration at the target, which is difficult to measure.


Input: Techniques that combine mass spectrometry and imaging techniques (matrix-assisted laser desorption/ionization, secondary ion mass spectrometry (SIMS), and nanoSIMS) have promise in addressing this problem.


Input: Emerging lymphae for the fountain of life.


Input: The lymphatic system is indispensable for the collection and cycling of tissue-extravasated fluids, macromolecules and immune cells into the bloodstream.


Input: Different mechanisms, including sprouting, ballooning and budding of lymphatic endothelial cells from the cardinal vein, have been proposed for lymphatic vessel formation during mammalial embryogenesis.


Input: H a gerling et al (2013) now provide a cell-scale model of lymphoangiogenesis by applying selective plane illumination-based ultramicroscopy (Becker et al, 2008) to wholemount-immunostained mouse embryos.


Input: They describe VEGFR-3, VEGF-C and CCBE1 as key regulators of lymphatic endothelial cell budding and migration at the early emergence of lymphatics from venous endothelium.


Input: Narrow bandgap colloidal metal chalcogenide quantum dots: synthetic methods, heterostructures, assemblies, electronic and infrared optical properties.


Input: The chemistry, material processing and fundamental understanding of colloidal semiconductor nanocrystals (quantum dots) are advancing at an astounding rate, bringing the prospects of widespread commercialization of these novel and exciting materials ever closer.


Input: Interest in narrow bandgap nanocrystals in particular has intensified in recent years, and the results of research worldwide point to the realistic prospects of applications for these materials in solar cells, infrared optoelectronics (e. g. lasers, optical modulators, photodetectors and photoimaging devices), low cost/large format microelectronics, and in biological imaging and biosensor systems to name only some technologies.


Input: Improvements in fundamental understanding and material quality are built on a vast body of experience spread over many different methods of colloidal synthetic growth, each with their own strengths and weaknesses for different materials and sometimes with regard to particular applications.


Input: The nanocrystal growth expertise is matched by a rapidly expanding, and highly interdisciplinary, understanding of how best to assemble these materials into films or hybrid composites and thereby into useful devices, and again there are many different strategies that can be adopted.


Input: In this review we have attempted to survey and compare the recent work on colloidal synthesis, film and nanocrystal composite material fabrication, concentrating on narrow bandgap chalcogenide materials and some of their topical applications in the solar energy and biological fields.

chalcogenide


Input: Since these applications are attracting rising interest across a wide range of disciplines, from the biological sciences, device engineering, and materials processing fields as well as the physics and synthetic chemistry communities, we have endeavoured to make the review of these narrow bandgap nanomaterials both comprehensive and accessible to newcomers to the area.


Input: Identification of a small-molecule inhibitor of HIV-1 assembly that targets the phosphatidylinositol (4, 5)-bisphosphate binding site of the HIV-1 matrix protein.

phosphatidylinositol (4, 5)-bisphosphate


Input: The development of drug resistance remains a critical problem for current HIV-1 antiviral therapies, creating a need for new inhibitors of HIV-1 replication.


Input: We previously reported on a novel anti-HIV-1 compound, N (2)-(phenoxyacetyl)-N-[4-(1-piperidinylcarbonyl) benzyl] glycinamide (14), that binds to the highly conserved phosphatidylinositol (4, 5)-bisphosphate (PI (4, 5) P (2)) binding pocket of the HIV-1 matrix (MA) protein.

N (2)-(phenoxyacetyl)-N-[4-(1-piperidinylcarbonyl) benzyl] glycinamide

phosphatidylinositol (4, 5)-bisphosphate

PI (4, 5) P (2)


Input: In this study, we re-evaluate the hits from the virtual screen used to identify compound 14 and test them directly in an HIV-1 replication assay using primary human peripheral blood mononuclear cells.


Input: This study resulted in the identification of three new compounds with antiviral activity; 2-(4-{[3-(4-fluorophenyl)-1, 2, 4-oxadiazol-5-yl] methyl})-1-piperazinyl)-N-(4-methylphenyl) acetamide (7), 3-(2-ethoxyphenyl)-5-[[4-(4-nitrophenyl) piperazin-1-yl] methyl]-1, 2, 4-oxadiazole (17), and N-[4-ethoxy-3-(1-piperidinylsulfonyl) phenyl]-2-(imidazo [2, 1-b] [1, 3] thiazol-6-yl) acetamide (18), with compound 7 being the most potent of these hits.

2-(4-{[3-(4-fluorophenyl)-1, 2, 4-oxadiazol-5-yl] methyl})-1-piperazinyl)-N-(4-methylphenyl) acetamide

3-(2-ethoxyphenyl)-5-[[4-(4-nitrophenyl) piperazin-1-yl] methyl]-1, 2, 4-oxadiazole

N-[4-ethoxy-3-(1-piperidinylsulfonyl) phenyl]-2-(imidazo [2, 1-b] [1, 3] thiazol-6-yl) acetamide


Input: Mechanistic studies on 7 demonstrated that it directly interacts with and functions through HIV-1 MA.


Input: In accordance with our drug target, compound 7 competes with PI (4, 5) P (2) for MA binding and, as a result, diminishes the production of new virus.

PI (4, 5) P (2)


Input: Mutation of residues within the PI (4, 5) P (2) binding site of MA decreased the antiviral effect of compound 7.

PI (4, 5) P (2)


Input: Additionally, compound 7 displays a broadly neutralizing anti-HIV activity, with IC (50) values of 7. 5-15. 6 mu M for the group M isolates tested.


Input: Taken together, these results point towards a novel chemical probe that can be used to more closely study the biological role of MA and could, through further optimization, lead to a new class of anti-HIV-1 therapeutics.


Input: CrbpI regulates mammary retinoic acid homeostasis and the mammary microenvironment.

retinoic acid


Input: Cellular retinol-binding protein, type I (CrbpI), encoded by retinol-binding protein, type 1 (Rbp1), is a chaperone of vitamin A (retinol) that is epigenetically silenced in ~ 25% of human breast cancers.

retinol

retinol

vitamin A

retinol


Input: CrbpI delivers vitamin A to enzymes for metabolism into an active metabolite, all-trans retinoic acid (atRA), where atRA is essential to cell proliferation, apoptosis, differentiation, and migration.

vitamin A

all-trans retinoic acid

atRA

atRA


Input: Here, we show the effect of CrbpI loss on mammary atRA homeostasis using the Rbp1 (-/-) mouse model.

atRA


Input: Rbp1 (-/-) mouse mammary tissue has disrupted retinoid homeostasis that results in 40% depleted endogenous atRA.

retinoid

atRA


Input: CrbpI loss and atRA depletion precede defects in atRA biosynthesis enzyme expression.

atRA

atRA


Input: Compensation by CrbpIII as a retinoid chaperone does not functionally replace CrbpI.

retinoid


Input: Mammary subcellular fractions isolated from Rbp1 (-/-) mice have altered retinol dehydrogenase/reductase (Rdh) enzyme activity that results in 24-42% less atRA production.

retinol

atRA


Input: Rbp1 (-/-) mammary tissue has epithelial hyperplasia, stromal hypercellularity, increased collagen, and increased oxidative stress characteristic of atRA deficiency and early tissue dysfunction that precedes tumor formation.

atRA


Input: Consistent with the findings from the Rbp1 (-/-) mouse, tumorigenic epithelial cells lacking CrbpI expression produce 51% less atRA.

atRA


Input: Together, these data show that CrbpI loss disrupts atRA homeostasis in mammary tissue, resulting in microenvironmental defects similar to those observed at the early stages of tumorigenesis.-Pierzchalski, K., Yu, J., Norman, V., Kane, M.

atRA


Input: A.


Input: CrbpI regulates mammary retinoic acid homeostasis and the mammary microenvironment.

retinoic acid


Input: Small-molecule-mediated axonal branching in Caenorhabditis elegans.


Input: An in vivo system for monitoring small-molecule-mediated neuronal branching has been developed by using C. elegans.


Input: Growth-promoting compounds can be detected by visual inspection of GFPlabeled cholinergic neurons, as axonal branching occurs following treatment with neurotrophic agents.


Input: Investigation of the structure-activity relationship of the neurotrophic natural product clovanemagnolol (1) led us to a comparable chemically edited derivative.

clovanemagnolol


Input: Multifarious roles of intrinsic disorder in proteins illustrate its broad impact on plant biology.


Input: Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes.


Input: Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs.


Input: Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein-protein interactions.


Input: Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners.


Input: In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs.


Input: Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development.


Input: Based on the roles of disorder in the protein-protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways.


Input: Mutations in the putative dimer-dimer interfaces of the measles virus hemagglutinin head domain affect membrane fusion triggering.


Input: Measles virus (MV), an enveloped RNA virus belonging to the Paramyxoviridae family, enters the cell through membrane fusion mediated by two viral envelope proteins, an attachment protein hemagglutinin (H) and a fusion (F) protein.


Input: The crystal structure of the receptor-binding head domain of MV-H bound to its cellular receptor revealed that the MV-H head domain forms a tetrameric assembly (dimer of dimers), which occurs in two forms (forms I and II).


Input: In this study, we show that mutations in the putative dimer-dimer interface of the head domain in either form inhibit the ability of MV-H to support membrane fusion, without greatly affecting its cell surface expression, receptor binding, and interaction with the F protein.


Input: Notably, some anti-MV-H neutralizing monoclonal antibodies are directed to the region around the dimer-dimer interface in form I rather than receptor-binding sites.


Input: These observations suggest that the dimer-dimer interactions of the MV-H head domain, especially that in form I, contribute to triggering membrane fusion, and that conformational shift of head domain tetramers plays a role in the process.


Input: Furthermore, our results indicate that although the stalk and transmembrane regions may be mainly responsible for the tetramer formation of MV-H, the head domain alone can form tetramers, albeit at a low efficiency.


Input: Sialylneolacto-N-tetraose c (LSTc)-bearing liposomal decoys capture influenza A virus.

Sialylneolacto-N-tetraose c

LSTc


Input: Influenza is a severe disease in humans and animals with few effective therapies available.


Input: All strains of influenza virus are prone to developing drug resistance due to the high mutation rate in the viral genome.


Input: A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of influenza.


Input: Influenza uses many individually weak ligand binding interactions for a high avidity multivalent attachment to sialic acid-bearing cells.

sialic acid


Input: Polymerized sialic acid analogs can form multivalent interactions with influenza but are not ideal therapeutics due to solubility and toxicity issues.

sialic acid


Input: We used liposomes as a novel means for delivery of the glycan sialylneolacto-N-tetraose c (LSTc).

sialylneolacto-N-tetraose c

LSTc


Input: LSTc-bearing decoy liposomes form multivalent, polymer-like interactions with influenza virus.

LSTc


Input: Decoy liposomes competitively bind influenza virus in hemagglutination inhibition assays and inhibit infection of target cells in a dose-dependent manner.


Input: Inhibition is specific for influenza virus, as inhibition of Sendai virus and respiratory syncytial virus is not observed.


Input: In contrast, monovalent LSTc does not bind influenza virus or inhibit infectivity.

LSTc


Input: LSTc decoy liposomes prevent the spread of influenza virus during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus.

LSTc


Input: LSTc decoy liposomes co-localize with fluorescently tagged influenza virus, whereas control liposomes do not.

LSTc


Input: Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high avidity interactions with influenza hemagglutinin, our decoy liposomes have potential as a new therapeutic agent against emerging influenza strains.


Input: Evidence for metal-surface interactions and their role in stabilizing well-defined immobilized Ru-NHC alkene metathesis catalysts.

Ru-NHC alkene


Input: Secondary interactions are demonstrated to direct the stability of well-defined Ru-NHC-based heterogeneous alkene metathesis catalysts.

Ru-NHC

alkene


Input: By providing key stabilization of the active sites, higher catalytic performance is achieved.


Input: Specifically, they can be described as interactions between the metal center (active site) and the surface functionality of the support, and they have been detected by surface-enhanced (1) H-(29) Si NMR spectroscopy of the ligand and (31) P solid-state NMR of the catalyst precursor.

(1) H

(29) Si

(31) P


Input: They are present only when the metal center is attached to the surface via a flexible linker (a propyl group), which allows the active site to either react with the substrate or relax, reversibly, to the surface, thus providing stability.

propyl


Input: In contrast, the use of a rigid linker (here mesitylphenyl) leads to a well-defined active site far away from the surface, stabilized only by a phosphine ligand which under reaction conditions leaves probably irreversibly, leading to faster decomposition and deactivation of the catalysts.

mesitylphenyl

phosphine


Input: Intercalation pathway in many-particle LiFePO4 electrode revealed by nanoscale state-of-charge mapping.


Input: The intercalation pathway of lithium iron phosphate (LFP) in the positive electrode of a lithium-ion battery was probed at the ~ 40 nm length scale using oxidation-state-sensitive X-ray microscopy.

lithium iron phosphate

LFP

lithium


Input: Combined with morphological observations of the same exact locations using transmission electron microscopy, we quantified the local state-of-charge of approximately 450 individual LFP particles over nearly the entire thickness of the porous electrode.

LFP


Input: With the electrode charged to 50% state-of-charge in 0. 5 h, we observed that the overwhelming majority of particles were either almost completely delithiated or lithiated.


Input: Specifically, only ~ 2% of individual particles were at an intermediate state-of-charge.


Input: From this small fraction of particles that were actively undergoing delithiation, we conclude that the time needed to charge a particle is ~ 1/50 the time needed to charge the entire particle ensemble.


Input: Surprisingly, we observed a very weak correlation between the sequence of delithiation and the particle size, contrary to the common expectation that smaller particles delithiate before larger ones.


Input: Our quantitative results unambiguously confirm the mosaic (particle-by-particle) pathway of intercalation and suggest that the rate-limiting process of charging is initiating the phase transformation by, for example, a nucleation-like event.


Input: Therefore, strategies for further enhancing the performance of LFP electrodes should not focus on increasing the phase-boundary velocity but on the rate of phase-transformation initiation.

LFP


Input: Pharmacological chaperones as therapeutics for lysosomal storage diseases.


Input: Lysosomal enzymes are responsible for the degradation of a wide variety of glycolipids, oligosaccharides, proteins, and glycoproteins.


Input: Inherited mutations in the genes that encode these proteins can lead to reduced stability of newly synthesized lysosomal enzymes.


Input: While often catalytically competent, the mutated enzymes are unable to efficiently pass the quality control mechanisms of the endoplasmic reticulum, resulting in reduced lysosomal trafficking, substrate accumulation, and cellular dysfunction.


Input: Pharmacological chaperones (PCs) are small molecules that bind and stabilize mutant lysosomal enzymes, thereby allowing proper cellular translocation.


Input: Such compounds have been shown to increase enzyme activity and reduce substrate burden in a number of preclinical models and clinical studies.


Input: In this Perspective, we review several of the lysosomal diseases for which PCs have been studied and the SAR of the various classes of molecules.


Input: In vitro study of injury on human bronchial epithelial cells caused by gunpowder smog.


Input: Smog inhalation is associated with acute respiratory symptoms in exposed victims.


Input: However, despite the evidence from cell injury caused by smog, a stable and practical apparatus used to treat cells with smog is necessary.


Input: The aim of this study is to develop a cell research platform of smoke inhalation injury.


Input: In the smog-generation device, a wireless electromagnetic heater was used to ignite gunpowder and generate smog.


Input: The quality of black powder was checked by the black powder burn rate, and experimental smog was indirectly checked by the amount of cell damage.


Input: The temperature and humidity were set at 37 degrees C +/- 1 degrees C and >= 95% in the smog-cells reaction chamber, respectively.


Input: Factors including gunpowder dosages, smog-exposure time, the cell density, modes of exposure, volumes of smog, test durations, volumes of the cell culture medium and combustion velocity were measured.


Input: Coefficient variation of different batches of gunpowder and smog were less than 4% and 9%, respectively.


Input: With larger gunpowder dosage and longer exposure time, cell injury appeared to increase.


Input: When cells were cultured in 4 x 10 (4)/well density in culture medium (1 mL/well), exposed to more than 10 L smog with filter screens above plates, detected after 24 h culture in cell incubator and gunpowder burned out within 5 s, smog had the best effect on cell injury.


Input: In conclusion, the experimental device can produce test smog stably and safely.


Input: The apparatus treating cells with smog can induce cell injury effectively, and the injury is positively correlated with smog concentration and exposure time.


Input: Computationally assisted assignment of kahalalide Y configuration using an NMR-constrained conformational search.

kahalalide Y


Input: Assignment of the absolute configuration of cyclic peptides frequently yields challenges, leaving one or more stereogenic centers unassigned due to small quantities of sample and the limited utility of Marfey' s or other methods for assigning amino or hydroxy acids.

amino or hydroxy acids


Input: Here, we report isolation of kahalalide Y (1) from Bryopsis pennata for the first time; in addition, the application of a combination of molecular modeling and NOE distance constraint calculations was utilized to determine the conformation of 1 and the absolute configuration of the final stereogenic center of 1.

kahalalide Y


Input: Using the Schr o dinger suite, the structure of 1 was sketched in Maestro and minimized using the OPLS2005 force field in Macromodel.


Input: A conformational search was performed separately for structures having an R or S configuration at C-3 of the beta-hydroxy fatty acid subunit that completes the cyclic scaffold of 1, after which multiple minimizations for all generated conformers were carried out.

beta-hydroxy fatty acid


Input: The lowest energy conformers of R and S stereoisomers were then subjected to B3LYP geometry optimizations including solvent effects.


Input: The S stereoisomer was shown to be in excellent agreement with the NOE-derived distance constraints and hydrogen-bonding stability studies.

hydrogen


Input: Surfactant adsorption and interfacial tension investigations on cyclopentane hydrate.

cyclopentane hydrate


Input: Gas hydrates represent an unconventional methane resource and a production/safety risk to traditional oil and gas flowlines.

methane


Input: In both systems, hydrate may share interfaces with both aqueous and hydrocarbon fluids.

hydrocarbon


Input: To accurately model macroscopic properties, such as relative permeability in unconventional systems or dispersion viscosity in traditional systems, knowledge of hydrate interfacial properties is required.


Input: This work presents hydrate cohesive force results measured on a micromechanical force apparatus, and complementary water-hydrocarbon interfacial tension data.

hydrocarbon


Input: By combining a revised cohesive force model with experimental data, two interfacial properties of cyclopentane hydrate were estimated: hydrate-water and hydrate-cyclopentane interfacial tension values at 0. 32 +/- 0. 05 mN/m and 47 +/- 5 mN/m, respectively.

cyclopentane hydrate

cyclopentane


Input: These fundamental physiochemical properties have not been estimated or measured for cyclopentane hydrate to date.

cyclopentane hydrate


Input: The addition of surfactants in the cyclopentane phase significantly reduced the cyclopentane hydrate cohesive force; we hypothesize this behavior to be the result of surfactant adsorption on the hydrate-oil interface.

cyclopentane

cyclopentane hydrate


Input: Surface excess quantities were estimated for hydrate-oil and water-oil interfaces using four carboxylic and sulfonic acids.

carboxylic and sulfonic acids


Input: The results suggest the density of adsorbed surfactant may be 2 x larger for the hydrate-oil interface than the water-oil interface.


Input: Additionally, hydrate-oil interfacial tension was observed to begin decreasing from the baseline value at significantly lower surfactant concentrations (1-3 orders of magnitude) than those for the water-oil interfacial tension.


Input: Neurotoxic potential and cellular uptake of T-2 toxin in human astrocytes in primary culture.

T-2 toxin


Input: The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed.

trichothecene

T-2 toxin


Input: The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin.

T-2 toxin


Input: However, only few data on neurotoxic properties of T-2 toxin are reported so far, but in vivo studies showed different effects of T-2 toxin on behavior as well as on levels of brain amines in animals.

T-2 toxin

T-2 toxin

amines


Input: To further investigate the cytotoxic properties of T-2 toxin on cells derived from brain tissue, normal human astrocytes in primary culture (NHA) were used in this study.

T-2 toxin


Input: Besides studies of cytotoxicity, apoptosis (caspase-3-activation, Annexin V) and necrosis (LDH-release), the cellular uptake and metabolism of T-2 toxin in NHA was analyzed and compared to the uptake in an established human cell line (HT-29).

T-2 toxin


Input: The results show that human astrocytes were highly sensitive to the cytotoxic properties of T-2 toxin, and apoptosis, induced at low concentrations, was identified for the first time as the mechanism of toxic action in NHA.

T-2 toxin


Input: Furthermore, a strong accumulation of T-2 toxin in NHA and HT-29 cells was detected, and T-2 toxin was subjected to metabolism leading to HT-2 toxin, a commonly found metabolite after T-2 toxin incubation in both cell types.

T-2 toxin

T-2 toxin

HT-2 toxin

T-2 toxin


Input: This formation seems to occur within the cells since incubations of T-2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin.

T-2 toxin


Input: The results of this study emphasize the neurotoxic potential of T-2 toxin in human astrocytes at low concentrations after short incubation times.

T-2 toxin


Input: Direct atomic-level observation and chemical analysis of ZnSe synthesized by in situ high-throughput reactive fiber drawing.

ZnSe


Input: We demonstrate a high-throughput method for synthesizing zinc selenide (ZnSe) in situ during fiber drawing.

zinc selenide

ZnSe


Input: Central to this method is a thermally activated chemical reaction occurring across multiple interfaces between alternately layered elemental zinc-(Zn-) and selenium-(Se-) rich films embedded in a preform and drawn into meters of fiber at a temperature well below the melting temperature of either Zn or ZnSe.

zinc

Zn

selenium

Se

Zn

ZnSe


Input: By depositing 50 nm thick layers of Zn interleaved between 1 mu m thick Se layers, a controlled breakup of the Zn sheet is achieved, thereby enabling a complete and controlled chemical reaction.

Zn

Se

Zn


Input: The thermodynamics and kinetics of this synthesis process are studied using thermogravimetric analysis and differential scanning calorimetry, and the in-fiber compound is analyzed by a multiplicity of materials characterization tools, including transmission electron microscopy, Raman microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction, all resulting in unambiguous identification of ZnSe as the compound produced from the reactive fiber draw.

ZnSe


Input: Furthermore, we characterize the in-fiber ZnSe/Se97S3 heterojunction to demonstrate the prospect of ZnSe-based fiber optoelectronic devices.

ZnSe

ZnSe


Input: The ability to synthesize new compounds during fiber drawing at nanometer scale precision and to characterize them at the atomic-level extends the architecture and materials selection compatible with multimaterial fiber drawing, thus paving the way toward more complex and sophisticated functionality.


Input: Zinc-dependent lysosomal enlargement in TRPML1-deficient cells involves MTF-1 transcription factor and ZnT4 (Slc30a4) transporter.

Zinc


Input: Zinc is critical for a multitude of cellular processes, including gene expression, secretion and enzymatic activities.

Zinc


Input: Cellular zinc is controlled by zinc-chelating proteins and by zinc transporters.

zinc

zinc

zinc


Input: The recent identification of zinc permeability of the lysosomal ion channel TRPML1 (transient receptor potential mucolipin 1), and the evidence of abnormal zinc levels in cells deficient in TRPML1, suggested a role for TRPML1 in zinc transport.

zinc

zinc

zinc


Input: In the present study we provide new evidence for such a role and identify additional cellular components responsible for it.


Input: In agreement with the previously published data, an acute siRNA (small interfering RNA)-driven TRPML1 KD (knockdown) leads to the build-up of large cytoplasmic vesicles positive for LysoTracker (TM) and zinc staining, when cells are exposed to high concentrations of zinc.

zinc

zinc


Input: We now show that lysosomal enlargement and zinc build-up in TRPML1-KD cells exposed to zinc are ameliorated by KD of the zinc-sensitive transcription factor MTF-1 (metal-regulatory-element-binding transcription factor-1) or the zinc transporter ZnT4.

zinc

zinc

zinc

zinc


Input: TRPML1 KD is associated with a build-up of cytoplasmic zinc and with enhanced transcriptional response of mRNA for MT2a (metallothionein 2a).

zinc


Input: TRPML1 KD did not suppress lysosomal secretion, but it did delay zinc leak from the lysosomes into the cytoplasm.

zinc


Input: These results underscore a role for TRPML1 in zinc metabolism.

zinc


Input: Furthermore, they suggest that TRPML1 works in concert with ZnT4 to regulate zinc translocation between the cytoplasm and lysosomes.

zinc


Input: Hydrogenated ZnO core-shell nanocables for flexible supercapacitors and self-powered systems.

ZnO


Input: Although MnO2 is a promising material for supercapacitors (SCs) due to its excellent electrochemical performance and natural abundance, its wide application is limited by poor electrical conductivity.


Input: Inspired by our results that the electrochemical activity and electrical conductivity of ZnO nanowires were greatly improved after hydrogenation, we designed and fabricated hydrogenated single-crystal ZnO @amorphous ZnO-doped MnO2 core-shell nanocables (HZM) on carbon cloth as SC electrodes, showing excellent performance such as areal capacitance of 138. 7 mF/cm (2) and specific capacitance of 1260. 9 F/g.

ZnO

ZnO

ZnO-doped MnO2

carbon


Input: Highly flexible all-solid-state SCs were subsequently assembled with these novel HZM electrodes using polyvinyl alcohol/LiCl electrolyte.

polyvinyl alcohol

LiCl


Input: The working devices achieved very high total areal capacitance of 26 mF/cm (2) and retained 87. 5% of the original capacitance even after 10 000 charge/discharge cycles.


Input: An integrated power pack incorporating series-wound SCs and dye-sensitized solar cells was demonstrated for stand-alone self-powered systems.


Input: Influence of chain length and double bond on the aqueous behavior of choline carboxylate soaps.

choline carboxylate


Input: In preceding studies, we demonstrated that choline carboxylates ChC (m) with alkyl chain lengths of m = 12-18 are highly water-soluble (for m = 12, soluble up to 93 wt% soap and 0 degrees C).

choline carboxylates ChC (m)

alkyl


Input: In addition, choline soaps are featured by an extraordinary lyotropic phase behavior.

choline


Input: With decreasing water concentration, the following phases were found: micellar phase (L (1)), discontinuous cubic phase (I (1)' and I (1) "), hexagonal phase (H (1)), bicontinuous cubic phase (V (1)), and lamellar phase (L (alpha)).


Input: The present work is also focused on the lyotropic phase behavior of choline soaps but with shorter alkyl chains or different alkyl chain properties.

choline

alkyl

alkyl


Input: We have investigated the aqueous phase behavior of choline soaps with C (8) and C (10) chain-lengths (choline octanoate and choline decanoate) and with a C (18) chain-length with a cis-double bond (choline oleate).

choline

C (8)

C (10)

choline octanoate

choline decanoate

C (18)

choline oleate


Input: We found that choline decanoate follows the lyotropic phase behavior of the longer-chain homologues mentioned above.

choline decanoate


Input: Choline octanoate in water shows no discontinuous cubic phases, but an extended, isotropic micellar solution phase.

Choline octanoate


Input: In addition, choline octanoate is at the limit between a surfactant and a hydrotrope.

choline octanoate


Input: The double bond in choline oleate leads also to a better solubility in water and a decrease of the solubilization temperature.

choline oleate


Input: It also influences the Gaussian curvature of the aggregates which results in a loss of discontinuous cubic phases in the binary phase diagram.


Input: The different lyotropic mesophases were identified by the penetration scan technique with polarizing light microscope and visual observations.


Input: To clarify the structural behavior small (SAXS) and wide (WAXS) angle X-ray scattering were performed.


Input: To further characterize the extended, isotropic micellar solution phase in the binary phase diagram of choline octanoate viscosity and conductivity measurements were also carried out.

choline octanoate


Input: Preparation, characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting.

donepezil

PLGA


Input: Abstract Objective: Alzheimer' s disease (AD) is a progressive neurodegenerative disorder manifested by cognitive, memory deterioration and variety of neuropsychiatric symptoms.


Input: Donepezil is a reversible cholinesterase inhibitor used for the treatment of AD.

Donepezil


Input: The purpose of this work is to prepare a nanoparticulate drug delivery system of donepezil using poly (lactic-co-glycolic acid) (PLGA) for sustained release and efficient brain targeting.

donepezil

poly (lactic-co-glycolic acid)

PLGA