Input: Control of one-dimensional magnetism in graphene via spontaneous hydrogenation of the grain boundary.

graphene


Input: We propose that control of one-dimensional (1D) magnetism in graphene could be made easier by spontaneous hydrogenation of chemically reactive grain boundaries (GBs) in polycrystalline graphenes.

graphene

graphenes


Input: Unlike pristine graphene, where hydrogen adsorption favors the formation of zero-dimensional (0D) clusters, the defect cores (pentagon, heptagon and octagon) at the GBs in polycrystalline graphene promote hydrogenation along the GBs.

graphene

hydrogen

graphene


Input: The hydrogenation in polycrystalline graphene starts at the GBs, proceeds gradually towards the grain interior (GI) and results in smooth 1D graphane-graphene interfaces.

graphene

graphane

graphene


Input: Our calculations show that the type (ferro-or antiferro-magnetism) and strength of the magnetism can be controlled by controlling the orientation of GBs.

ferro


Input: Since GBs in single-layer graphenes can be fabricated in a controllable way in experiments, the hydrogenation of GBs could be a unique method to realize large-area magnetic graphenes for future spintronic applications.

graphenes

graphenes


Input: HDL Cholesterol Subfractions and the Effect of Testosterone Replacement in Hypogonadism.

Cholesterol

Testosterone


Input: Metabolic disorders and cardiovascular events are increased in hypogonadism.


Input: Serum HDL composition is a better cardiovascular predictor than the HDL counts.


Input: However, there is no information about the HDL subfractions in patients with hypogonadism.


Input: We designed a prospective study to investigate the HDL subfractions in treatment na i ve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions.

testosterone


Input: Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study.


Input: The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily.

testosterone esters


Input: Biochemical investigations including HDL subfractions and insulin resistance were done.


Input: Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure.

triglyceride


Input: Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels.

cholesterol


Input: The total testosterone levels were independent determinants of the HDL2 subfractions.

testosterone


Input: During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed.

cholesterol

cholesterol


Input: No difference was present between the 2 treatment arms.


Input: These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features.


Input: However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition.

testosterone


Input: Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism.


Input: Hierarchical NiO microflake films with high coloration efficiency, cyclic stability and low power consumption for applications in a complementary electrochromic device.

NiO


Input: We have demonstrated that thin films of hierarchical NiO microflakes assembled from nanoleaves can be grown directly on FTO-coated glass substrates using a facile and template-free hydrothermal technique.

NiO

FTO


Input: This hierarchical structure holds the advantages of both nanometre-sized building blocks and microsized assemblies.


Input: Thus, the films exhibit highly enhanced electrochromic performances and cyclic stability due to their high surface area and good electrochemical stability.


Input: Moreover, a complementary electrochromic device combining the hierarchical NiO microflake film with a self-weaving WO3 nanoflake film is fabricated to further improve the electrochromic performance.

NiO


Input: As a result, the complementary electrochromic device shows a high optical modulation (73. 2% at 550 nm), large coloration efficiency (146. 9 cm (2) C (-1) at 550 nm by applying a low coloration voltage of-1. 0 V) and fast switching responses with a coloring time of 1. 8 s and a bleaching time of 3. 2 s.


Input: It is also observed that there is no significant degradation of the electrochromic properties after 2000 continuous coloration/bleaching cycles, making it attractive for practical applications.


Input: Design, synthesis, and biological evaluation of cyclopropyl analogues of stilbene with raloxifene side chain as subtype-selective ligands for estrogen receptor.

cyclopropyl

stilbene

raloxifene

estrogen


Input: We have designed the cyclopropane analog of stilbene as subtype-selective ligands for estrogen receptor based on the bioisosterism that cyclopropane could act as alkene bioisoster.

cyclopropane

stilbene

estrogen

cyclopropane

alkene


Input: Three cyclopropane analogs were prepared efficiently starting from 4-benzyloxybenzaldehyde, and evaluated for their binding to estrogen receptors ER alpha and ER beta.

cyclopropane

estrogen


Input: These cyclopropane analogs were also found to be full agonists in estrogen receptor-mediated gene transcription assay.

cyclopropane

estrogen


Input: Compared to the stilbene analogs such as tamoxifen and raloxifene, the three cyclopropane analogs showed lower binding affinity for estrogen receptor, but higher subtype selectivity for ER alpha.

stilbene

tamoxifen

raloxifene

cyclopropane

estrogen


Input: The structure-activity relationship revealed from this study might provide clues for improving subtype selectivity for ER alpha.


Input: A Biodegradable Polymersome Containing Bcl-xL siRNA and Doxorubicin as a Dual Delivery Vehicle for a Synergistic Anticancer Effect.

Doxorubicin


Input: Combined cancer treatment via co-delivery of siRNAs and an anticancer drug can be a promising strategy due to the synergistic effect of simultaneously minimizing gene/drug administration.


Input: In this study, Bcl-xL siRNA and doxorubicin (DOX) are encapsulated into designed methoxy-poly (ethylene glycol)-block-poly (D, L-lactic acid) (mPEG-b-PLA) block copolymer polymersomes (PSomes).

doxorubicin

DOX

methoxy

poly (ethylene glycol)

poly (D, L-lactic acid)

mPEG

PLA


Input: A study of the cytotoxicity of Bcl-xL siRNA and DOX co-encapsulated PSomes (CPSomes) shows more inhibited proliferation of MKN-45 and MKN-28 human gastric cancer cell lines than only gene-and drug-loaded ones.

DOX


Input: Consequently, these results demonstrate that co-delivery of genes and drugs using PSomes results in a synergistic efficacy and indicates the potential of PSomes as efficient nanocarriers for combined cancer therapy.


Input: Intestinal bacterial transformation-a nonnegligible part of Chinese medicine research.


Input: Intestinal bacteria play an essential part in the metabolism of the constituents of herbal drugs, and a lot of investigations have been done to unveil their functions and mechanisms in modification of these constituents and their effect.


Input: This review provides a progressive description of intestinal bacterial transformation with respect to properties, reactions, correlation with the effect of herbal drugs, research interests, and methodology.


Input: In addition, the problems encountered during the investigation are addressed and perspectives are proposed.


Input: Glycosides from the bark of Machilus robusta.


Input: Six new glycosidic constituents (1-6), together with 10 known analogs, have been isolated from the bark of Machilus robusta.


Input: Structures of the new compounds, including the absolute configurations, were determined by spectroscopic and chemical methods as (-)-nectandrin B-beta-d-glucopyranoside (1), (-)-(7R, 7' R, 8S, 8' R)-4, 4'-dihydroxy-3, 3'-dimethoxy-7, 7'-epoxylignan-4-O-beta-d-glucopyranoside (2), (-)-(7R, 7' R, 8S, 8' R)-4, 4'-dihydroxy-3, 3'-dimethoxy-7, 7'-epoxylignan-4'-O-beta-d-glucopyranoside (3), (-)-(8S, 8' R)-4, 4'-dihydroxy-3, 3', 5'-trimethoxylignan-4'-O-beta-d-glucopyranoside (4), (-)-(7R, 8R)-syringylglycerol-8-O-beta-d-glucopyranoside (5), and (-)-3-hydroxy-2-methyl-4-pyrone-3-O-beta-d-xylopyranosyl-(1 --> 6)-O-beta-d-glucopyranoside (6), respectively.

(-)-nectandrin B-beta-d-glucopyranoside

(-)-(7R, 7' R, 8S, 8' R)-4, 4'-dihydroxy-3, 3'-dimethoxy-7, 7'-epoxylignan-4-O-beta-d-glucopyranoside

(-)-(7R, 7' R, 8S, 8' R)-4, 4'-dihydroxy-3, 3'-dimethoxy-7, 7'-epoxylignan-4'-O-beta-d-glucopyranoside

(-)-(8S, 8' R)-4, 4'-dihydroxy-3, 3', 5'-trimethoxylignan-4'-O-beta-d-glucopyranoside

(-)-(7R, 8R)-syringylglycerol-8-O-beta-d-glucopyranoside

(-)-3-hydroxy-2-methyl-4-pyrone-3-O-beta-d-xylopyranosyl-(1 --> 6)-O-beta-d-glucopyranoside


Input: Terpenoids from the Chinese liverwort Plagiochila pulcherrima and their cytotoxic effects.

Terpenoids


Input: Three new pimarane-type diterpenoids, 7 beta, 11 alpha-dihydroxypimara-8 (14), 15-diene (1), 1 beta, 11 alpha-dihydroxypimara-8 (14), 15-diene (2), and 11 alpha-hydroxypimara-8 (14), 15-diene (3), five 2, 3-secoaromadendrane-type sesquiterpenoids, including a new one, ethyoxyplagiochiline A2 (4), and three known fusicoccane-type diterpenoids were isolated from the Chinese liverwort Plagiochila pulcherrima.

pimarane

diterpenoids

7 beta, 11 alpha-dihydroxypimara-8 (14), 15-diene

1 beta, 11 alpha-dihydroxypimara-8 (14), 15-diene

11 alpha-hydroxypimara-8 (14), 15-diene

2, 3-secoaromadendrane

sesquiterpenoids

ethyoxyplagiochiline A2

fusicoccane

diterpenoids


Input: Their structures were established on the basis of extensive spectroscopic analysis.


Input: Compounds 6 and 7 exhibited moderate inhibitory activity on the proliferation of human cancer cell lines Hela, A172, and H460.


Input: Moreover, the cytotoxicity of compound 6 to Hela cells was related to apoptotis as confirmed by DAPI nuclear staining and flow cytometry.


Input: Development of 2'-substituted (2S, 1' R, 2' S)-2-(carboxycyclopropyl) glycine analogues as potent N-methyl-D-aspartic acid receptor ligands.

2'-substituted (2S, 1' R, 2' S)-2-(carboxycyclopropyl) glycine

N-methyl-D-aspartic acid


Input: A series of 2'-substituted analogues of the selective NMDA receptor ligand (2S, 1' R, 2' S)-2-(carboxycyclopropyl) glycine ((S)-CCG-IV) have been designed, synthesized and pharmacologically characterized.

NMDA

(2S, 1' R, 2' S)-2-(carboxycyclopropyl) glycine

(S)-CCG-IV


Input: The design was based on a docking study hypothesizing that substituents in the 2'-position would protrude into a region where differences among the NMDA receptors GluN2 subunits exist.

NMDA


Input: Various synthetic routes were explored, and two different routes provided a series of alkyl-substituted analogues.


Input: Pharmacological characterization disclosed that these compounds are NMDA receptor agonists and that potency decreases with increasing size of the alkyl groups.

NMDA


Input: Variations in agonist activity are observed at recombinant NMDA receptor subtypes with increasing size of the alkyl-substituents and are developing differently depending on the GluN2 subunit.

NMDA


Input: This study demonstrates that it is possible to introduce substituents in the 2'-position of (S)-CCG-IV while maintaining agonist activity and that variation among NMDA receptor subtypes may be achieved by probing this region of the receptor.

(S)-CCG-IV

NMDA


Input: Safety concerns with the long-term management of osteoporosis.


Input: Introduction: Postmenopausal osteoporosis is a chronic disease that exerts a significant burden on both individuals and the community.


Input: Hence, there is a requirement for long-term treatment to be associated with a positive benefit-risk balance.


Input: Areas covered: In this descriptive review, the long-term safety of calcitonin, selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab and strontium ranelate was reviewed based on randomized controlled trials of 3 years or longer supplemented by extension study data and data from large, observational studies.

estrogen

bisphosphonates

strontium ranelate


Input: Expert opinion: Rare adverse events become apparent with all currently available treatments for osteoporosis with long-term therapy.


Input: Due to the rarity of these adverse events and to the worldwide burden of osteoporosis, the benefit-risk balance remains in favor of the beneficial effects of treatment on an outcome rather than the probability of an adverse effect.


Input: No single antiosteoporosis agent is appropriate for all patients.


Input: Treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations.


Input: Dimerized Glycosaminoglycan Chains Increase FGF Signaling during Zebrafish Development.


Input: Proteoglycans (PGs) modulate numerous signaling pathways during development through binding of their glycosaminoglycan (GAG) side chains to various signaling molecules, including fibroblast growth factors (FGFs).


Input: A majority of PGs possess two or more GAG side chains, suggesting that GAG multivalency is imperative for biological functions in vivo.


Input: However, only a few studies have examined the biological significance of GAG multivalency.


Input: In this report, we utilized a library of bis-and tris-xylosides that produce two and three GAG chains on the same scaffold, respectively, thus mimicking PGs, to examine the importance of GAG valency and chain type in regulating FGF/FGFR interactions in vivo in zebrafish.

bis-and tris-xylosides


Input: A number of bis-and tris-xylosides, but not mono-xylosides, caused an elongation phenotype upon their injection into embryos.

bis-and tris-xylosides

mono-xylosides


Input: In situ hybridization showed that elongated embryos have elevated expression of the FGF target gene mkp3 but unchanged expression of reporters for other pathways, indicating that FGF/FGFR signaling was specifically hyperactivated.


Input: In support of this observation, elongation can be reversed by the tyrosine kinase inhibitor SU5402, mRNA for the FGFR antagonist sprouty4, or FGF8 morpholino.


Input: Endogenous GAGs seem to be unaffected after xyloside treatment, suggesting that this is a gain-of-function phenotype.

xyloside


Input: Furthermore, expression of a multivalent but not a monovalent GAG containing syndecan-1 proteoglycan recapitulates the elongation phenotype observed with the bivalent xylosides.

xylosides


Input: On the basis of these in vivo findings, we propose a new model for GAG/FGF/FGFR interactions in which dimerized GAG chains can activate FGF-mediated signal transduction pathways.


Input: Conversion of Aristolochic Acid I into Aristolic Acid by Reaction with Cysteine and Glutathione: Biological Implications.

Aristolochic Acid I

Aristolic Acid

Cysteine

Glutathione


Input: Aristolochic acid I (AA-I), naturally occurring in Aristolochia plants, is a potent nephrotoxin and carcinogen.

Aristolochic acid I

AA-I


Input: Here we report that AA-I suffers hydrogenolysis with loss of the nitro group by reaction with cysteine or glutathione to give aristolic acid.

AA-I

nitro

cysteine

glutathione

aristolic acid


Input: Since the reaction can proceed in aqueous solutions at pH 7. 0 and 37 degrees C, it is inferred that it may also occur in biological systems and contribute to the nephrotoxic effects induced by AA-I.

AA-I


Input: Adenovirus-delivered angiopoietin-1 treatment for phosgene-induced acute lung injury.

phosgene


Input: Abstract Context: Exposure to phosgene can result in an acute lung injury, leading to pulmonary edema and even death.

phosgene


Input: Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization due to its ability to reduce endothelial permeability and inflammation.


Input: Objective: In this study, the histopathological changes of the lungs after exposure to phosgene and the effect of Ang1 treatment were examined.

phosgene


Input: Materials and methods: Rats were exposed to phosgene gas at 8. 33 g/m (3) for 5 min.

phosgene


Input: Ang1 overexpressing rats were established by an intravenous injection of adenovirus-Ang1 (Ad/Ang1).


Input: The histological changes of the lung were examined by Haematoxylin-Eosin (H & E) staining and fluorescence microscopy.

Haematoxylin

Eosin


Input: The inferior lobe was used for the determination of the ratio of wet weight to dry weight of the lung.


Input: The concentration of cytokines in the serum and bronchoalveolar lavage fluid was determined by enzyme-linked immunosorbent assay.


Input: Results: The pathological analysis showed signs of inflammation and edema, evident from a significant increase in the number of leukocytes in bronchoalveolar lavage fluid and the ratio of wet to dry weight of the lungs.


Input: The lung injury induced by phosgene was markedly reduced after the injection of Ad/Ang1.

phosgene


Input: The increase of IL-1 beta and IL-17 and decrease of vascular endothelial growth factor in the serum and bronchoalveolar lavage fluid of phosgene-exposed animals were abolished by the administration of Ad/Ang1.

phosgene


Input: Discussion and conclusions: Ang1 has the beneficial effects on phosgene-induced lung injury.

phosgene


Input: The adenovirus-delivered Ang1 may have the potential as a novel approach for the treatment of the acute lung injury caused by phosgene gas inhalation in humans.

phosgene


Input: Recycling factors for ribosome disassembly in the apicoplast and mitochondrion of Plasmodium falciparum.


Input: The reduced genomes of the apicoplast and mitochondrion of the malaria parasite Plasmodium falciparum are actively translated and antibiotic-mediated translation inhibition is detrimental to parasite survival.


Input: In order to understand recycling of organellar ribosomes, a critical step in protein translation, we identified ribosome recycling factors (RRF) encoded by the parasite nuclear genome.


Input: Targeting of PfRRF1 and PfRRF2 to the apicoplast and mitochondrion respectively was established by localization of leader sequence-GFP fusions.


Input: Unlike any RRF characterized thus far, PfRRF2 formed dimers with disulphide interaction (s) and additionally localized in the cytoplasm, thus suggesting adjunct functions for the factor.

disulphide


Input: PfRRF1 carries a large 108-amino-acid insertion in the functionally critical hinge region between the head and tail domains of the protein, yet complemented Escherichia coli RRF in the LJ14frr (ts) mutant and disassembled surrogate E. coli 70S ribosomes in the presence of apicoplast-targeted EF-G.

amino-acid


Input: Recombinant PfRRF2 bound E. coli ribosomes and could split monosomes in the presence of the relevant mitochondrial EF-G but failed to complement the LJ14frr (ts) mutant.


Input: Although proteins comprising subunits of P. falciparum organellar ribosomes are predicted to differ from bacterial and mitoribosomal counterparts, our results indicate that the essential interactions required for recycling are conserved in parasite organelles.


Input: Two new compounds from Schisandra glaucescens.


Input: One new lignan (7S, 8R, 7' R, 8' R)-7-(3, 4-methylenedioxyphenyl)-8, 8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3', 4'-methylenedioxyphenyl)-tetrahydrofuran (1), one new sesquiterpene 2-hydroxy-11, 12-dehydrocalamenene (2), one new natural product erythro-1-(3, 4-dimethoxyphenyl)-4-(3, 4-methylenedioxyphenyl)-2, 3-dimethyl-butane (3), and two known lignans (+)-anwulignan (erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3, 4-methylenedioxyphenyl)-2, 3-dimethyl-butane) (4) and (-)-zuonin-A (5) were isolated from the stems of Schisandra glaucescens Diels.

(7S, 8R, 7' R, 8' R)-7-(3, 4-methylenedioxyphenyl)-8, 8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3', 4'-methylenedioxyphenyl)-tetrahydrofuran

2-hydroxy-11, 12-dehydrocalamenene

erythro-1-(3, 4-dimethoxyphenyl)-4-(3, 4-methylenedioxyphenyl)-2, 3-dimethyl-butane

lignans (+)-anwulignan (erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3, 4-methylenedioxyphenyl)-2, 3-dimethyl-butane)

(-)-zuonin-A


Input: Their structures were elucidated by spectroscopic methods.


Input: The cytotoxicity of compounds 1 and 2 was assayed.


Input: Influence of different polymers on crystallization tendency and dissolution behavior of cilnidipine in solid dispersions.

cilnidipine


Input: Abstract Context: Cilnidipine (CN) is a novel dihydropyridine calcium antagonist that is practically insoluble in aqueous media and exhibits a low oral bioavailability or limited clinical efficacy.

Cilnidipine

dihydropyridine calcium


Input: Objective: This study investigated the effects of three commercial and chemically diverse polymers-PVP, PVP/VA and Soluplus-on crystallization tendency and in vitro dissolution profiles of CN in order to determine an optimum carrier for composing the preferred solid dispersion (SD) of CN.

PVP

PVP

Soluplus


Input: Methods: All these co-evaporated systems were characterized up to 3 months by thermoanalytical (DSC), crystallographic (POM, PXRD), microscopic (SEM) and spectroscopic (FTIR) techniques.


Input: Results: The results showed that the polymers could be sorted by their effects of inhibiting CN crystallization in the ascending order: Soluplus, PVP/VA, PVP.

Soluplus

PVP

PVP


Input: The sequence was in accordance with that of the strength of drug-polymer hydrogen bonds revealed by FTIR spectra.


Input: It could be ascribed to relative hydrogen-bonding acceptor strengths of N-vinylpyrrolidone moiety in the polymer molecules.

hydrogen

N-vinylpyrrolidone


Input: On the other hand, all the SDs showed enhanced dissolution profiles compared to pure CN alone.


Input: On their effects of enhancing CN dissolution, the polymers could be sorted in the descending order: Soluplus, PVP, PVP/VA.

Soluplus

PVP

PVP


Input: Conclusions: It implied that the dissolution behavior of CN could bear a close relationship to both hydration capacity and hydrogen-bonding interaction tendency of moieties of the polymers.

hydrogen


Input: It might suggest an optimal formulation for CN comprising both PVP and Soluplus.

PVP

Soluplus


Input: Bile Acid and Sterol Metabolism with Combined HMGCoA Reductase and PCSK9 Suppression.

Bile Acid

Sterol


Input: PCSK9 inhibition markedly augments the LDL lowering action of statins.


Input: The combination is being evaluated for long-term effects on atherosclerotic disease outcomes.


Input: However, effects of combined treatment on hepatic cholesterol and bile acid metabolism have not yet been reported.

cholesterol

bile acid


Input: To study this, PCSK9-Y119X mutant (knockout) and wild type mice were treated +/- atorvastatin for 12 wks.

atorvastatin


Input: Atorvastatin progressively lowered plasma LDL in each group, but no differences in liver cholesterol, cholesterol ester, or total bile acid concentrations, or in plasma total bile acid levels were seen.

Atorvastatin

cholesterol

cholesterol ester

bile acid

bile acid


Input: In contrast, atorvastatin increased fecal total bile acids (~ 2-fold, P < 0. 01) and cholesterol concentrations (~ 3-fold, P < 0. 01) vs. controls for both PCSK9-Y119X and wild type mice.

atorvastatin

bile acids

cholesterol


Input: All 14 individual bile acids resolved by LC-MS, including primary, secondary, and conjugated species, reflected similar increases.

bile acids


Input: Expression of key liver bile acid synthesis genes CYP7A1 and CYP8B1 were ~ 2. 5-fold higher with atorvastatin in both strains, but mRNA for liver bile acid export and reuptake transporters and conjugating enzymes were not unaffected.

bile acid

atorvastatin

bile acid


Input: The data suggest that hepatocyte cholesterol and bile acid homeostasis is maintained with combined PCSK9 and HMGCoA reductase inhibition through efficient liver enzymatic conversion of LDL-derived cholesterol into bile acids and excretion of both, with undisturbed enterohepatic recycling.

cholesterol

bile acid

cholesterol

bile acids


Input: Tea and human health: The dark shadows.


Input: Tea is one of the most popularly consumed beverage.


Input: Depending on the manufacturing process, different varieties of tea can be produced.


Input: The antioxidative and antimutagenic potential of tea in cardiovascular diseases, cancer and obesity have long been studied.


Input: These therapeutic and nutritional benefits of tea can be attributed to the presence of flavanoids.

flavanoids


Input: However, these flavanoids also have certain detrimental effects on human health when their consumption exceeds certain limits.

flavanoids


Input: The toxicity of these flavanoids can be attributed to the formation of reactive oxygen species in the body which causes damage to the DNA, lipid membranes etc.

flavanoids

oxygen


Input: The aim of this review is to summarize briefly, the less studied evidences of various forms of toxicity associated with tea and its harmful effects on human health.


Input: High-Throughput Analytical Model to Evaluate Materials for Temperature Swing Adsorption Processes.


Input: In order for any material to be considered in a post-combustion carbon capture technology, it must have high working capacities of CO2 from flue gas and be regenerable using as little energy as possible.


Input: Shown here is an easy to use method to calculate both working capacities and regeneration energies and thereby predict optimal desorption conditions for any material.


Input: Common variation in PPARGC1A/B and progression to diabetes or change in metabolic traits following preventive interventions: the Diabetes Prevention Program.


Input: AIMS/HYPOTHESIS: PPARGC1A and PPARGC1B encode transcriptional coactivators that regulate numerous type 2 diabetes-related metabolic processes.


Input: Common genetic variation across PPARGC1A/B was characterised by genotyping tagging variants.


Input: We then tested associations of these variants with diabetes incidence or change in quantifiable metabolic traits directly or via interactions (with metformin treatment or intensive lifestyle modification) in the Diabetes Prevention Program (DPP), a randomised controlled trial in persons at high risk of type 2 diabetes.

metformin


Input: METHODS: We used Tagger software to select 75 PPARGC1A and 94 PPARGC1B tag single nucleotide polymorphisms (SNPs) for analysis.


Input: These SNPs were tested for association with diabetes incidence using Cox proportional hazards regression models, and a range of relevant metabolic quantifiable traits, using generalised linear models.


Input: RESULTS: Eight PPARGC1A variants were nominally (p < 0. 05) associated with diabetes incidence, of which one (rs3736265/Thr612Met) was associated with diabetes in the DPP (HR 1. 31, 95% CI 1. 05, 1. 63 per copy of the 612Met allele) and in the DIAGRAM database (OR 1. 11, 95% CI 1. 01, 1. 21).


Input: Consistent with earlier reports, the Gly482Ser (rs8192678) variant showed nominally significant effects on 1 year accumulation of adiposity and worsening insulin resistance (both p < 0. 05).


Input: A third PPARGC1A variant (rs2970852) modified the effects of metformin on triacylglycerol levels (p interaction = 0. 04; p = 0. 0001 for association of SNP with triacylglycerol concentrations in metformin-treated participants).

metformin

triacylglycerol

triacylglycerol

metformin


Input: A number of other PPARGC1A/B variants were nominally directly associated with diabetes incidence or modified treatment effects on diabetes incidence.


Input: CONCLUSIONS/INTERPRETATION: These findings provide some novel and confirmatory insights into the roles of PPARGC1A/B variation in type 2 diabetes and related metabolic traits.


Input: TRIAL REGISTRATION: ClinicalTrials. gov NCT00004992.


Input: Flexible Low-Voltage Organic Transistors with High Thermal Stability at 250 degrees C.


Input: Low-operating-voltage flexible organic thin-film transistors with high thermal stability using DPh-DNTT and SAM gate dielectrics are reported.

DPh-DNTT


Input: The mobility of the transistors are decreased by 23% after heating to 250 degrees C for 30 min.


Input: Furthermore, flexible organic pseudo-CMOS inverter circuits, which are functional after heating to 200 degrees C.


Input: Click To Bind: Metal Sensors.


Input: The copper-catalyzed azide-alkyne " click " cycloaddition reaction is an efficient coupling reaction that results in the formation of a triazole ring.

copper

azide-alkyne

triazole


Input: The wide range of applicable substrates for this reaction allows the construction of a variety of conjugated systems.


Input: The additional function of triazoles as metal-ion ligands has led to the click reaction being used for the construction of optical sensors for metal ions.

triazoles


Input: The triazoles are integral binding elements, which are formed in an efficient modular synthesis.

triazoles


Input: Herein, we review recent examples of triazoles as a metal-binding element in conjugated metal-ion sensors.

triazoles


Input: Solvent Induced Luminescence Quenching: Static and Time-Resolved X-Ray Absorption Spectroscopy of a Copper (I) Phenanthroline Complex.

Copper (I) Phenanthroline


Input: We present a static and picosecond X-ray absorption study at the Cu K-edge of Bis (2, 9-dimethyl-1, 10-phenanthroline) copper (I) ([Cu (dmp) 2] +; dmp = 2, 9-dimethyl-1, 10-phenanthroline) dissolved in acetonitrile and dichloromethane.

Cu

Bis (2, 9-dimethyl-1, 10-phenanthroline) copper (I)

[Cu (dmp) 2] +

dmp

2, 9-dimethyl-1, 10-phenanthroline

acetonitrile

dichloromethane


Input: The steady state photoluminescence spectra in dichloromethane and acetonitrile are also presented and show a shift to longer wavelengths for the latter, which points to a stronger stabilisation of the excited complex.

dichloromethane

acetonitrile


Input: The fine structure features of the static and transient X-ray spectra allow an unambiguous assignment of the electronic and geometric structure of the molecule in both its ground and excited 3MLCT states.


Input: Importantly, the transient spectra are remarkably similar for both solvents and the spectral changes can be rationalised using the optimised ground and excited state structures of the complex.


Input: The proposed assignment of the lifetime shortening of the excited state in donor solvents (acetonitrile) to a metal centred exciplex is not corroborated here.

acetonitrile


Input: Molecular dynamics simulations confirm the lack of complexation, however in both solvents the molecules come close to the metal but undergo rapid exchange with the bulk.


Input: The shortening of the lifetime of the title complex and nine additional related complexes can be rationalised by the decrease of the 3MLCT energy.


Input: Deviations from this trend may be explained by means of the effects of the dihedral angle between the ligand planes, the solvent and the 3MLCT-1MLCT energy gap.


Input: Carbon Xerogel Microspheres and Monoliths from Resorcinol-Formaldehyde Mixtures with Varying Dilution Ratios: Preparation, Surface Characteristics, and Electrochemical Double-Layer Capacitances.

Carbon

Resorcinol

Formaldehyde


Input: Carbon xerogels in the form of microspheres and monoliths were obtained from the sol-gel polymerization of resorcinol and formaldehyde in the presence of potassium carbonate as catalyst, using water as solvent and two different molar dilution ratios.

resorcinol

formaldehyde

potassium carbonate


Input: The objectives of this study were as follows: to investigate the effect of the dilution ratio, polymerization reaction time, and temperature on the rheological properties of the sols used to prepare the carbon xerogel microspheres and monoliths; and to determine the influence of their preparation methods and shapes on their surface characteristics and electrochemical double-layer (EDL) capacitance.

carbon


Input: An increase in the molar dilution ratio produced a decrease in the apparent activation energy of the sol-gel transition.


Input: Carbon xerogel microspheres were steam-activated at different burnoff percentages.

Carbon


Input: The morphology, surface area, porosity, and surface chemistry of samples were determined.


Input: The main difference between the carbon xerogel microspheres and monoliths was that the latter are largely mesoporous.

carbon


Input: Better electrochemical behavior was shown by carbon xerogels in monolith than in microsphere form, but higher gravimetric and volumetric capacitances were found in activated carbon xerogel microspheres than in carbon xerogel monoliths.

carbon

carbon

carbon


Input: N3-substituted thymidine bioconjugates for cancer therapy and imaging.

N3-substituted thymidine


Input: The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer.

3-carboranyl thymidine

boron

boron


Input: Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1.


Input: Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors.


Input: This review presents an overview on the design, synthesis, and biological evaluation of first-and second-generation 3CTAs.


Input: Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described.

N3-substituted thymidine


Input: In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed.

carborane

boron


Input: Praziquantel Derivatives with Anti-Schistosomal Activity: Aromatic ring Modification.

Praziquantel


Input: A series of aromatic ring modified praziquantel (PZQ) derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin.

praziquantel

PZQ


Input: Several analogues comparable in activity to the drug PZQ have been identified based on in vitro and in vivo japonuicum schistosomes worm viability assay.

PZQ


Input: Structure and activity relationship of these PZQ aromatic ring modified compounds was revealed.

PZQ


Input: Specifically, a compound in which a bromine has been introduced in the aromatic ring of praziquantel demonstrated close antischistosomal activity to praziquentel in vivo.

bromine

praziquantel

praziquentel


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Competitive Adsorption of Di-hydroxy and Tri-hydroxy Bile Salts with Whey Protein and Casein in Oil-in-Water Emulsions.

Di-hydroxy and Tri-hydroxy Bile Salts


Input: The competitive adsorption between whey protein concentrate (WPC) or sodium caseinate (SCN) and four bile salts, sodium cholate (NaC), dexocycholate (NaDC), taurocholate (NaTC) and glycodeoxycholate (NaGDC) has been studied in protein stabilized oil-in-water emulsions.

sodium

bile salts

sodium cholate

NaC

dexocycholate

NaDC

taurocholate

NaTC

glycodeoxycholate

NaGDC


Input: The bile salts that contain a conjugated amino acid (NaTC and NaGDC) were considerably more efficient at displacing both WPC and SCN proteins from the emulsion droplet interface, even though they are known to have a lower hydrophobicity than NaC and NaDC.

amino acid

NaTC

NaGDC

NaC

NaDC


Input: This is explained in terms of a steric resistance to adsorption from the conjugated amino acids in NaTC and NaGDC.

amino acids

NaTC

NaGDC


Input: This leads to them adopting an adsorbed conformation at the oil-water interface that penetrates less into the oil phase causing greater disruption of the adsorbed layer and hence leads to greater displacement of protein from the interface.


Input: Complementary computer simulations of the adsorption of the four bile salts at the decane-water interface support the hypothesis that the NaTC and NaGDC adopt flatter conformations that stick out further in to the aqueous phase, which arises from a lower free energy of adsorption.

bile salts

decane

NaTC

NaGDC


Input: The adsorption isotherms for the four bile salts have also been measured.

bile salts


Input: These have been found to have a form that fits closely the Langmuir-Freundlich isotherm.


Input: The results for NaC suggest that it adsorbs as individual molecules and forms a saturated monolayer over much of the concentration range used in the displacement experiments, since it is below its critical micelle concentration in this range.

NaC


Input: For the other three bile salts on the other hand, the primary adsorbing species appears to be the micelle form, since the surface coverage is above that of a saturated monolayer for much of the concentration range studied.

bile salts


Input: Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In beta-Cells With Improved Aqueous Solubility.


Input: We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced beta-cell apoptosis.


Input: Herein, we report the synthesis and biological evaluation of 1 and analogs with improved aqueous solubility.


Input: By replacing naphthyl with quinoline moieties, we prepared active analogs with up to a 1400-fold increase in solubility from 1.

naphthyl

quinoline


Input: In addition, we demonstrated that compound 1 and analogs inhibit STAT1 signal transduction induced by IFN-gamma.


Input: The Differences in the Sublimation Energy of Benzene and Hexahalogenbenzenes Are Caused by Dispersion Energy.

Benzene

Hexahalogenbenzenes


Input: The crystals of benzene and hexahalogenbenzenes have been studied by means of the density-functional theory augmented by an empirical dispersion correction term as well as by the symmetry-adapted perturbation theory.

benzene

hexahalogenbenzenes


Input: In order to elucidate the nature of noncovalent binding, pairwise interactions have been investigated.


Input: It has been demonstrated that the structures of dimers with the highest stabilization energy differ notably along the crystals.


Input: It has been shown that the differences in the experimental sublimation energies might be attributed to the dispersion interaction.


Input: To our surprise, the dihalogen bonding observed in the hexachloro-and hexabromobenzenes plays a rather minor role in energy stabilization, because they are energetically comparable with the other binding motifs.

dihalogen

hexachloro-and hexabromobenzenes


Input: However, the dihalogen bond is by far the most frequent binding motif in hexachloro-and hexabromobenzenes.

dihalogen

hexachloro-and hexabromobenzenes


Input: High-resolution transcriptional analysis of the regulatory influence of cell-to-cell signalling reveals novel genes that contribute to Xanthomonas phytopathogenesis.


Input: The bacterium Xanthomonas campestris is an economically important pathogen of many crop species and a model for the study of bacterial phytopathogenesis.


Input: In X. campestris, a regulatory system mediated by the signal molecule DSF controls virulence to plants.


Input: The synthesis and recognition of the DSF signal depends upon different Rpf proteins.


Input: DSF signal generation requires RpfF whereas signal perception and transduction depends upon a system comprising the sensor RpfC and regulator RpfG.


Input: Here we have addressed the action and role of Rpf/DSF signalling in phytopathogenesis by high-resolution transcriptional analysis coupled to functional genomics.


Input: We detected transcripts for many genes that were unidentified by previous computational analysis of the genome sequence.


Input: Novel transcribed regions included intergenic transcripts predicted as coding or non-coding as well as those that were antisense to coding sequences.


Input: In total, mutation of rpfF, rpfG and rpfC led to alteration in transcript levels (more than fourfold) of approximately 480 genes.


Input: The regulatory influence of RpfF and RpfC demonstrated considerable overlap.


Input: Contrary to expectation, the regulatory influence of RpfC and RpfG had limited overlap, indicating complexities of the Rpf signalling system.


Input: Importantly, functional analysis revealed over 160 new virulence factors within the group of Rpf-regulated genes.


Input: Lactobacillus rhamnosus GG reduces hepatic TNF alpha production and inflammation in chronic alcohol-induced liver injury.


Input: The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models.


Input: Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation.


Input: Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal gram-negative bacteria in ALD.


Input: In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-alpha (TNF alpha) production and inflammation in response to chronic alcohol ingestion.


Input: Mice were fed Lieber DeCarli liquid diet containing 5% alcohol for 8weeks, and Lactobacillus rhamnosus GG (LGG) was supplemented in the last 2 weeks.


Input: Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay.


Input: Two weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNF alpha expression.


Input: Alcohol feeding increased hepatic mRNA expression of Toll-like receptors (TLRs) and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression.


Input: LGG supplementation attenuated these changes.


Input: Using human peripheral blood monocytes-derived macrophages, we also demonstrated that incubation with ethanol primes both lipopolysaccharide-and flagellin-induced TNF alpha production, and LGG culture supernatant reduced this induction in a dose-dependent manner.

ethanol


Input: In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase.


Input: In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNF alpha production via inhibition of TLR4-and TLR5-mediated endotoxin activation.


Input: Structure-activity relationships in aminosterol antibiotics: The effect of stereochemistry at the 7-OH group.

aminosterol


Input: Squalamine and three aminosterol analogs have been shown to inhibit bacterial cell growth and induce lysis of large unilamellar phospholipid vesicles.

Squalamine

aminosterol


Input: The analogs differ in the identity of the polyamine attached at C3 of the sterol, and the stereochemistry of a hydroxyl substituent at C7.

polyamine

sterol

hydroxyl


Input: Analogs with a tetraammonium spermine polyamine are somewhat more active than analogs with a shorter trisammonium spermidine polyamine, and analogs with an axial (alpha) hydroxyl substituent at C7 are more active than analogs with the corresponding equatorial (beta) hydroxyl group.

tetraammonium spermine polyamine

trisammonium spermidine polyamine

hydroxyl


Input: There is some variability noted; the 7 beta-OH spermine analog is the most active compound against Escherichia coli, but the least effective against Pseudomonas aeruginosa.

7 beta-OH spermine


Input: Lytic activity correlates well with antimicrobial activity of the compounds, but the lytic activity varies with the phospholipid composition of the vesicles.


Input: Interlaboratory evaluation of a cow' s milk allergy mouse model to assess the allergenicity of hydrolysed cow' s milk based infant formulas.


Input: This study describes two phases of a multi-phase project aiming to validate a mouse model for cow' s milk allergy to assess the potential allergenicity of hydrolysed cow' s milk based infant formulas (claim support EC-directive 2006/141/E).


Input: The transferability and the discriminatory power of this model was evaluated in 4 research centers.


Input: Mice were sensitized by oral gavage with whey or extensively hydrolysed whey (eWH) using cholera toxin as an adjuvant.


Input: Whey-specific antibodies, mMCP-1 levels, anaphylactic shock symptoms, body temperature and the acute allergic skin response were determined upon whey challenge.


Input: In phases I and II, all 4 centers detected elevated levels of whey-specific IgE/IgG1 in whey sensitized animals.


Input: Elevated levels of mMCP-1, anaphylactic symptoms, body temperature drop and acute allergic skin response were scored upon whey challenge in 3 out of 4 research centers.


Input: In contrast, none of the evaluated parameters were elevated in eWH orally exposed groups.


Input: The cow' s milk allergy mouse model is capable to distinguish the sensitizing capacity of complete or hydrolysed cow' s milk protein.


Input: The model uses straightforward parameters relevant to food allergic responses and can be effectively transferred between different laboratories.


Input: We propose this mouse model as a new strategy for the screening of new hypoallergenic cow' s milk formulas.


Input: Concurrent Regulation of the Transcription Factors Nrf2 and ATF4 Mediates the Enhancement of Glutathione Levels by the Flavonoid Fisetin.

Glutathione

Flavonoid Fisetin


Input: Glutathione (GSH) and GSH-associated metabolism provide the major line of defense for the protection of cells from various forms of toxic stress.

Glutathione

GSH

GSH


Input: GSH also plays a key role in regulating the intracellular redox environment.

GSH


Input: Thus, maintenance of GSH levels is developing into an important therapeutic objective for the treatment of a variety of diseases.

GSH


Input: Among the transcription factors that play critical roles in GSH metabolism are NF-E2-related factor 2 (Nrf2) and activating transcription factor 4 (ATF4).

GSH


Input: Thus, compounds that can upregulate these transcription factors may be particularly useful as treatment options through their effects on GSH metabolism.

GSH


Input: We previously showed that the flavonoid fisetin not only increases basal levels of GSH but also maintains GSH levels under oxidative stress conditions.

flavonoid fisetin

GSH

GSH


Input: However, the mechanisms underlying these effects have remained unknown until now.


Input: Here we show that fisetin rapidly increases the levels of both Nrf2 and ATF4 as well as Nrf2-and ATF4-dependent gene transcription via distinct mechanisms.

fisetin


Input: Although fisetin greatly increases the stability of both Nrf2 and ATF4, only the effect on ATF4 is dependent on protein kinase activity.

fisetin


Input: Using siRNA we found that ATF4, but not Nrf2, is important for fisetin' s ability to increase GSH levels under basal conditions whereas both ATF4 and Nrf2 appear to cooperate to increase GSH levels under oxidative stress conditions.

fisetin

GSH

GSH


Input: Based upon these results, we hypothesize that compounds able to increase GSH levels via multiple mechanisms, such as fisetin, will be particularly effective for maintaining GSH levels under a variety of different stresses.

GSH

fisetin

GSH


Input: Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-kappa B inactivation and cytokine suppression.


Input: ETHNOPHARMACOLOGICAL RELEVANCE: The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF).


Input: The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro.


Input: MATERIALS AND METHODS: The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF.


Input: From this, electrocardiographic parameters and exterior signs of rat hearts were recorded.


Input: Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured.


Input: Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle.


Input: Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control.

Captopril


Input: Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-kappa B activity luciferase reporter assay systems.


Input: Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-kappa B inhibitors from YQFM.


Input: RESULTS: The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) in CHF rats.


Input: Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed.

ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3


Input: Among these compounds, ginsenoside Ro was revealed as a new NF-kappa B inhibitor.

ginsenoside Ro


Input: CONCLUSION: The results suggested that NF-kappa B inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF.

ginsenosides


Input: Zebrafish as a model organism to study host-pathogen interactions.


Input: Zebrafish have been extensively used in biomedical research as a model to study vertebrate development but it is only recently that it has also been adopted into varied fields such as immunology and host-pathogen interactions.


Input: Zebrafish have a rapid life cycle, small size and the adults exhibit no territorial behavior in relatively dense cages.


Input: Under standard conditions each female lays an average of a hundred eggs per clutch, providing a large number of larvae per week.


Input: Their transparency during early life stages allows real time visualization of the different organs, which makes them especially suitable for the study of bacterial host-pathogen interactions.


Input: Traditionally, these studies have been technically challenging in higher organisms, given the loss of control over the bacteria once the pathogen infects its host.


Input: Here we describe an emerging approach to monitor Salmonella typhimurium infection progression using in vivo fluorescence upon parenteral infection.


Input: We have engineered Salmonella with the Cascade expression system; an efficient method to voluntarily activate bacterial heterologous gene expression at any point during infection once inside the Zebrafish macrophages, using a non-toxic inducer.


Input: Novel oral anticoagulants: clinical pharmacology, indications and practical considerations.


Input: BACKGROUND: Novel oral anticoagulants are approved in several indications: rivaroxaban, apixaban, and dabigatran for the prevention of venous thromboembolism after elective hip or knee replacement surgery, and edoxaban for hip or knee replacement surgery and hip fracture surgery (in Japan only); rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE; and rivaroxaban, apixaban, and dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

rivaroxaban

apixaban

dabigatran

edoxaban

rivaroxaban

rivaroxaban

apixaban

dabigatran


Input: These agents overcome some limitations of traditional anticoagulants, are suggested to have no requirement for routine coagulation monitoring, and are administered orally.


Input: Rivaroxaban, apixaban, and dabigatran have different pharmacological characteristics, and guidance is needed on optimum doses and dosing intervals and the effects of renal or hepatic impairment, age, food, and other drugs.

Rivaroxaban

apixaban

dabigatran


Input: Dabigatran has stricter prescribing advice than rivaroxaban or apixaban for patients with moderate-to-severe renal impairment.

Dabigatran

rivaroxaban

apixaban


Input: All three drugs have restrictions on use in patients with hepatic impairment.


Input: Apixaban requires twice-daily dosing in all indications, whereas rivaroxaban and dabigatran are dosed once-or twice-daily depending on indication.

Apixaban

rivaroxaban

dabigatran


Input: Although head-to-head comparisons are lacking, the novel oral anticoagulants may show favorable cost-benefit relations compared with traditional vitamin K antagonists or no therapy.

vitamin K


Input: AIM: This review summarizes the pharmacology of rivaroxaban, apixaban, edoxaban, and dabigatran, and the indications for which they are approved.

rivaroxaban

apixaban

edoxaban

dabigatran


Input: Issues regarding the optimization of the use of these anticoagulants for the management of thromboembolic disorders will also be discussed.


Input: Soluble polysialylated NCAM: a novel player of the innate immune system in the lung.


Input: Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity.

polysialic acid

polySia


Input: Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung.

polySia


Input: In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells.

polySia


Input: In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed.

polySia


Input: Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1 beta.

bleomycin


Input: As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1 beta or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM.

polySia

polySia


Input: Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing " neutrophil extracellular traps ", which are formed during invasion of microorganisms.

polySia


Input: Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes.

polySia


Input: In Vitro Neo-cartilage Formation on a Three-Dimensional Composite Polymeric Cryogel Matrix.


Input: Limited blood supply and the avascular nature of articular cartilage restricts its self repair capacity, frequently leading to osteoarthritis.


Input: This work focuses on scaffolds for tissue repair from natural polymers, for example gelatin, chitosan, and agarose in the form of composite.


Input: A novel way of fabrication, known as cryogelation, is presented, in which matrices are synthesized at sub-zero temperature.


Input: Cell seeded scaffolds incubated under appropriate conditions result in the accumulation of matrix components on the surface of the gel in the form of neo-cartilage.


Input: Neo-cartilage exhibits similarity to native cartilage with respect to its physical, mechanical and biochemical properties.


Input: Based on the similarities of neo-cartilage to the native cartilage, it can provide a new approach for the treatment of localised joint injuries.


Input: Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding.


Input: AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear.


Input: To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD).


Input: METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined.

glucose


Input: Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle.


Input: RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks.

Glucose


Input: Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance.


Input: Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal.

glucose


Input: Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect.


Input: Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin.

Diacylglycerol

sphingomyelin


Input: Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance.


Input: CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.


Input: Structural changes in supercooled Al2O3-Y2O3 liquids.


Input: Structural changes in liquids between Al2O3 and Y2O3 are investigated as a function of the composition and during supercooling using high energy X-ray diffraction (HEXRD) techniques combined with containerless aerodynamic levitation.


Input: Many-body molecular dynamics simulation techniques utilizing potential models that incorporate anion polarization effects are applied to study the same liquid systems.


Input: The X-ray scattering experiments indicate a change in liquid structure during supercooling around a composition 20% Y2O3 (AlY20) that occurs over a narrow temperature interval.


Input: We have associated this change in structure with the onset of a liquid-liquid phase transformation.


Input: Analysis of the MD simulated structures has allowed the structure changes to be interpreted in terms of Al (3 +) and Y (3 +) coordination environments and particularly the Y (3 +)-Y (3 +) structural correlations.

Al (3 +)

Y (3 +)

Y (3 +)

Y (3 +)


Input: We show that the incipient liquid-liquid phase transition behaviour is correlated with local density fluctuations that represent different coordination polyhedra surrounding oxygen ions.

oxygen


Input: The difference in energy and volume associated with this sampling of high and low density basins in the underlying energy landscape is consistent with independent verifications of the volume and enthalpy differences between different amorphous forms.


Input: The differences in the high-and low-density configurations match the difference in diffraction patterns observed experimentally.


Input: Trastuzumab Emtansine: First Global Approval.


Input: Genentech and ImmunoGen are collaborating on the development of trastuzumab emtansine, a HER2 antibody-drug conjugate that comprises Genentech' s trastuzumab antibody linked to ImmunoGen' s anti-mitotic agent, mertansine (a maytansine derivative; also known as DM1).

mertansine

maytansine


Input: The conjugate combines two strategies: the anti-HER2 activity of trastuzumab, and the targeted intracellular delivery of mertansine, a tubulin polymerisation inhibitor which interferes with mitosis and promotes apoptosis.

mertansine


Input: The linker in trastuzumab emtansine is a non-reducible thioether linker, N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC, designated MCC after conjugation).

thioether

N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate

SMCC

MCC


Input: Trastuzumab emtansine (Kadcyla (TM)) has been launched in the USA as second-line monotherapy for HER2-positive metastatic breast cancer, and has been filed for approval in the EU and Japan in this indication.


Input: Trastuzumab emtansine is in phase III development as first-line combination therapy or monotherapy for metastatic HER2-positive breast cancer, and as third-line monotherapy for metastatic HER2-positive breast cancer.


Input: Phase II development is underway for early-stage breast cancer and phase II/III development is underway in patients with HER2-positive gastric cancer.


Input: This article summarizes the milestones in the development of trastuzumab emtansine leading to this first approval for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.

taxane


Input: Insulin degludec and insulin degludec/insulin aspart: a review of their use in the management of diabetes mellitus.


Input: Insulin degludec (Tresiba ((R))) is an ultra-long-acting insulin analogue that is also available as a coformulation with rapid-acting insulin aspart (insulin degludec/insulin aspart) [Ryzodeg ((R))].


Input: Insulin degludec has a flat, stable glucose-lowering profile with a duration of action of > 42 h, and less within-patient day-to-day variability in glucose-lowering effect than the long-acting insulin analogue insulin glargine.

glucose

glucose


Input: In clinical trials, insulin degludec achieved similar glycaemic control to that seen with insulin glargine in patients with type 1 or 2 diabetes, but with a lower risk of nocturnal hypoglycaemia.


Input: In addition, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes show the potential for adjusting the injection time, without compromising glycaemic control or safety.


Input: A 200 U/mL formulation of insulin degludec is also available for use in patients who require large volumes of basal insulin.


Input: Insulin degludec/insulin aspart was noninferior to the long-acting insulin analogue insulin detemir in patients with type 1 diabetes and has the potential to reduce the number of daily injections.


Input: Trial results also indicate that insulin degludec/insulin aspart may be an appropriate option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs.


Input: Subcutaneous insulin degludec was generally well tolerated in patients with type 1 or 2 diabetes.


Input: In conclusion, insulin degludec and insulin degludec/insulin aspart represent a useful advance in the treatment of type 1 or 2 diabetes.


Input: Study of endothelial cell apoptosis using fluorescence resonance energy transfer (FRET) biosensor cell line with hemodynamic microfluidic chip system.


Input: To better understand how hyperglycemia induces endothelial cell dysfunction under the diabetic conditions, a hemodynamic microfluidic chip system was developed.


Input: The system combines a caspase-3-based fluorescence resonance energy transfer (FRET) biosensor cell line which can detect endothelial cell apoptosis in real-time, post-treatment effect and with a limited cell sample, by using a microfluidic chip which can mimic the physiological pulsatile flow profile in the blood vessel.


Input: The caspase-3-based FRET biosensor endothelial cell line (HUVEC-C3) can produce a FRET-based sensor protein capable of probing caspase-3 activation.


Input: When the endothelial cells undergo apoptosis, the color of the sensor cells changes from green to blue, thus sensing apoptosis.


Input: A double-labeling fluorescent technique (yo pro-1 and propidium iodide) was used to validate the findings revealed by the FRET-based caspase sensor.

yo pro-1

propidium iodide


Input: The results show high rates of apoptosis and necrosis of endothelial cells when high glucose concentration was applied in our hemodynamic microfluidic chip combined with an exhaustive pulsatile flow profile.

glucose


Input: The two apoptosis detection techniques (fluorescent method and FRET biosensor) are comparable; but FRET biosensor offers more advantages such as real-time observation and a convenient operating process to generate more accurate and reliable data.


Input: Furthermore, the activation of the FRET biosensor also confirms the endothelial cell apoptosis induced by the abnormal pulsatile shear stress and high glucose concentration is through caspase-3 pathway.

glucose


Input: A 12% apoptotic rate (nearly a 4-fold increase compared to the static condition) was observed when the endothelial cells were exposed to a high glucose concentration of 20 mM under 2 h exhaustive pulsatile shear stress of 30 dyne cm (-2) and followed with another 10 h normal pulsatile shear stress of 15 dyne cm (-2).

glucose


Input: Therefore, the most important finding of this study is to develop a novel endothelial cell apoptosis detection method, which combines the microfluidic chip system and FRET biosensor.


Input: This finding may provide new insight into how glucose causes endothelial cell dysfunction, which is the major cause of diabetes-derived complications.

glucose


Input: Enantiomeric fraction determination of 2-arylpropionic acids in a package plant membrane bioreactor.

2-arylpropionic acids


Input: Enantiomeric compositions of three 2-arylpropionic acid (2-APA) drugs, ibuprofen, naproxen, and ketoprofen, were monitored in a membrane bioreactor (MBR) treating municipal effluent in a small rural town in Australia.

2-arylpropionic acid

ibuprofen

naproxen

ketoprofen


Input: Specific enantiomers were determined as amide diastereomers using the chiral derivatizing reagent, (R)-1-phenylethylamine (PEA), followed by gas chromatography-tandem mass spectrometry (GC-MS/MS).

amide

PEA


Input: The six individual enantiomers were quantified by isotope dilution and the enantiomeric fractions (EFs) were determined.


Input: Over four separate sampling events, ibuprofen EF ranged from 0. 88 to 0. 94 (median 0. 93) in the influent and 0. 38 to 0. 40 (median 0. 39) in the effluent.

ibuprofen


Input: However, no significant change in ketoprofen EF was observed, with influent EFs of 0. 56-0. 60 (median 0. 58) and effluent EFs 0. 54-0. 68 (median 0. 56).

ketoprofen


Input: This is the first report of enantiospecific analysis of ketoprofen in municipal wastewater and it is not yet clear why such different behavior was observed compared to ibuprofen.

ketoprofen

ibuprofen


Input: Naproxen EF was consistently measured at 0. 99 in the influent and ranged from 0. 86 to 0. 94 (median 0. 91) in the effluent.

Naproxen


Input: This study demonstrates that EF is a relatively stable parameter and does not fluctuate according to concentration or other short-term variables introduced by sampling limitations.


Input: The enantiospecific analysis of chiral chemicals presents a promising approach to elucidate a more thorough understanding of biological treatment processes and a potential tool for monitoring the performance of key biological pathways.


Input: Chirality 25: 301-307, 2013.


Input: (c) 2013 Wiley Periodicals, Inc.


Input: Homeodomain-interacting protein kinase 2-dependent repression of myogenic differentiation is relieved by its caspase-mediated cleavage.


Input: Differentiation of skeletal muscle cells is accompanied by drastic changes in gene expression programs that depend on activation and repression of genes at defined time points.


Input: Here we identify the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) as a corepressor that inhibits myocyte enhancer factor 2 (MEF2)-dependent gene expression in undifferentiated myoblasts.

serine

threonine


Input: Downregulation of HIPK2 expression by shRNAs results in elevated expression of muscle-specific genes, whereas overexpression of the kinase dampens transcription of these genes.


Input: HIPK2 is constitutively associated with a multi-protein complex containing histone deacetylase (HDAC) 3 and HDAC4 that serves to silence MEF2C-dependent transcription in undifferentiated myoblasts.


Input: HIPK2 interferes with gene expression on phosphorylation and HDAC3-dependent deacetylation of MEF2C.


Input: Ongoing muscle differentiation is accompanied by elevated caspase activity, which results in caspase-mediated cleavage of HIPK2 following aspartic acids 916 and 977 and the generation of a C-terminally truncated HIPK2 protein.

C


Input: The short form of the kinase loses its affinity to the repressive multi-protein complex and its ability to bind HDAC3 and HDAC4, thus alleviating its repressive function for expression of muscle genes.


Input: This study identifies HIPK2 as a further protein that determines the threshold and kinetics of gene expression in proliferating myoblasts and during the initial steps of myogenesis.


Input: Diabetic Retinopathy and Microalbuminuria Can Predict Macroalbuminuria and Renal Function Decline in Japanese Type 2 Diabetic Patients: Japan Diabetes Complications Study.


Input: OBJECTIVETo examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients, and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline. RESEARCH DESIGN AND METHODSWe explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (< 150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification.


Input: Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA (DR-)] (n = 773), normoalbuminuria with DR [NA (DR +)] (n = 279), microalbuminuria without DR [MA (DR-)] (n = 277), and microalbuminuria with DR [MA (DR +)] (n = 146).


Input: Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8. 0 years. RESULTSAnnual incidence rates of macroalbuminuria were 1. 6/1, 000 person-years (9 incidences), 3. 9/1, 000 person-years (8 incidences), 18. 4/1, 000 person-years (34 incidences), and 22. 1/1, 000 person-years (22 incidences) in the four groups, respectively.


Input: Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2. 48 (95% CI 0. 94-6. 50; P = 0. 07), 10. 40 (4. 91-22. 03; P < 0. 01), and 11. 55 (5. 24-25. 45; P < 0. 01) in NA (DR +), MA (DR-), and MA (DR +), respectively, in comparison with NA (DR-).


Input: Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA (DR +) (-1. 92 mL/min/1. 73 m (2)/year) than in the other groups. CONCLUSIONSIn normo-and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years.


Input: Patients with microalbuminuria and DR showed the fastest GFR decline.


Input: Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients.


Input: An open sharing of information will benefit both ophthalmologists and diabetologists.


Input: Inhibition of CYP2C19 and CYP3A4 by Omeprazole Metabolites and their Contribution to Drug-Drug Interactions.

Omeprazole


Input: The aim of this study was to evaluate the contribution of metabolites to drug-drug interactions (DDI) using the inhibition of CYP2C19 and CYP3A4 by omeprazole and its metabolites as a model.

omeprazole


Input: Of the metabolites identified in vivo, 5-hydroxyomeprazole, 5'-O-desmethylomeprazole, omeprazole sulfone and carboxyomeprazole had an AUCm/AUCp >= 0. 25 when either total or unbound concentrations were measured following a single 20 mg dose of omeprazole in a cocktail.

omeprazole sulfone

carboxyomeprazole

omeprazole


Input: All of the metabolites inhibited CYP2C19 and CYP3A4 reversibly.


Input: In addition omeprazole, omeprazole sulfone and 5'-O-desmethylomeprazole were mechanism-based inhibitors (MBI) of CYP2C19 while omeprazole and 5'-O-desmethylomeprazole were found to be MBIs of CYP3A4.

omeprazole

omeprazole sulfone

omeprazole


Input: Reversible [I]/Ki ratios and irreversible lambda/kdeg ratios were used to evaluate whether characterization of the metabolites affected DDI risk assessment.


Input: Identifying omeprazole as an MBI of both CYP2C19 and CYP3A4 was the most important factor in DDI risk assessment.

omeprazole


Input: Consideration of reversible inhibition by omeprazole and its metabolites would not identify DDI risk with CYP3A4, and with CYP2C19 reversible inhibition values would only identify DDI risk if the metabolites are included in the assessment.

omeprazole


Input: Based on inactivation data, CYP2C19 and CYP3A4 inactivation by omeprazole would be sufficient to identify risk, but metabolites were predicted to contribute 30-63% to the in vivo hepatic interactions.

omeprazole


Input: Hence, consideration of metabolites may be important in quantitative predictions of in vivo DDIs.


Input: The results of this study show that while metabolites contribute to in vivo DDIs their relative abundance in circulation or logP values do not predict their contribution to in vivo DDI risk.


Input: GALACTOSYLATED MICELLES FOR A RIBAVIRIN PRODRUG TARGETING TO HEPATOCYTES.

RIBAVIRIN


Input: Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, i. e., ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate.

ribavirin

RBV

carbohydrate

galactosylated polylactide-polyaminoacid


Input: This latter was obtained by chemical reaction of alpha, beta-poly (N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer.

alpha, beta-poly (N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide

PHEA-EDA

polylactic acid

PLA

lactose

PHEA-EDA-PLA-GAL


Input: To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, i. e. RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated.

RBV

RBV tripalmitate

RBV


Input: Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size.

RBV tripalmitate

PHEA-EDA-PLA-GAL


Input: By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL.

RBV tripalmitate

PHEA-EDA-PLA-GAL

GAL


Input: This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.


Input: Uncovering the Enzymes that Catalyze the Final Steps in Oxytetracycline Biosynthesis.

Oxytetracycline


Input: Tetracyclines are a group of natural products sharing a linearly fused four-ring scaffold, which is essential for their broad-spectrum antibiotic activities.

Tetracyclines


Input: Formation of the key precursor anhydrotetracycline 3 during oxytetracycline 1 biosynthesis has been previously characterized.

anhydrotetracycline

oxytetracycline


Input: However, the enzymatic steps that transform 3 into 1, including the additional hydroxylation at C5 and the final C5a-C11a reduction, have remained elusive.


Input: Here we report two redox enzymes, OxyS and OxyR, are sufficient to convert 3 to 1.


Input: OxyS catalyzes two sequential hydroxylations at C6 and C5 positions of 3 with opposite stereochemistry, while OxyR catalyzes the C5a-C11a reduction using F420 as a cofactor to produce 1.


Input: The crystal structure of OxyS was obtained to provide insights into the tandem C6-and C5-hydroxylation steps.


Input: The substrate specificities of OxyS and OxyR were shown to influence the relative ratio of 1 and tetracycline 2.

tetracycline


Input: Highly Confined Tunable Mid-Infrared Plasmonics in Graphene Nanoresonators.

Graphene


Input: Single-layer graphene has been shown to have intriguing prospects as a plasmonic material, as modes having plasmon wavelengths ~ 20 times smaller than free space (lambda p ~ lambda 0/20) have been observed in the 2-6 THz range, and active graphene plasmonic devices operating in that regime have been explored.

graphene

graphene


Input: However there is great interest in understanding the properties of graphene plasmons across the infrared spectrum, especially at energies exceeding the graphene optical phonon energy.

graphene

graphene


Input: We use infrared microscopy to observe the modes of tunable plasmonic graphene nanoresonator arrays as small as 15 nm.

graphene


Input: We map the wavevector-dependent dispersion relations for graphene plasmons at mid-infrared energies from measurements of resonant frequency changes with nanoresonator width.

graphene


Input: By tuning resonator width and charge density, we probe graphene plasmons with lambda p <= lambda 0/100 and plasmon resonances as high as 310 meV (2500 cm (-1)) for 15 nm nanoresonators.

graphene


Input: Electromagnetic calculations suggest that the confined plasmonic modes have a local density of optical states more than 10 (6) larger than free space and thus could strongly increase light-matter interactions at infrared energies.


Input: Synthesis and Cytotoxic Evaluation of Acylated Brefeldin A Derivatives as Potential Anticancer Agents.

Acylated Brefeldin A


Input: Brefeldin A (BFA) has attracted considerable attention because of its potential function in cancer prevention.

Brefeldin A

BFA


Input: However, its therapeutic use is limited by its poor bioavailability.


Input: The modifications on BFA were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule.

BFA

hydroxyl


Input: In this study, we report the selective acylation of BFA under mild conditions and the preparation of a series of monoacylated and diacylated BFA derivatives.

BFA

monoacylated and diacylated BFA


Input: Their cytotoxicity, antitumor activity against TE-1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated.


Input: BFA 7-O-benzoate, BFA 4, 7-O-dibenzoate, and BFA 7-O-biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0. 39, 0. 46, and 0. 50 mu M respectively.

BFA 7-O-benzoate

BFA 4, 7-O-dibenzoate

BFA 7-O-biotin carboxylate


Input: Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO.

guanine nucleotide


Input: Our results may serve as a basis for the development of novel potential anti-cancer agents from BFA derivatives.

BFA


Input: This article is protected by copyright.


Input: All rights reserved.


Input: Synthesis and antifungal evaluation of pentyloxyl-diphenylisoxazoloyl pneumocandins and echinocandins.

pentyloxyl

diphenylisoxazoloyl pneumocandins

echinocandins


Input: Echinocandins and pneumocandins are classes of lipocyclohexapeptides that are broad spectrum antifungal agents.

Echinocandins

pneumocandins

lipocyclohexapeptides


Input: They inhibit fungal specific 1, 3-beta-glucan synthase activity which is an essential component of the fungal cell wall.


Input: Chemical modifications of these two leads have produced three clinical agents namely caspofungin, micafungin and anidulafungin.

caspofungin

micafungin

anidulafungin


Input: The presence of hydroxy-glutamine versus threonine and unsaturated linear fatty acid versus branched chain saturated fatty acid differentiate the two classes of compounds with profound differences in their hemolytic properties.

hydroxy-glutamine

threonine

unsaturated linear fatty acid

branched chain saturated fatty acid


Input: In the current study, we have replaced the side chain of the cyclohexapeptides with a common aromatic heterocyclic acyl side chain and compared the biological activities of the cores head-to-head and for the first time demonstrated the role played by the acyl chain and the hydroxy-glutamine for the antifungal potency.

cyclohexapeptides

acyl

acyl

hydroxy-glutamine


Input: Facile synthesis of new imidazo [1, 2-a] pyridines carrying 1, 2, 3-triazoles via click chemistry and their antiepileptic studies.

imidazo [1, 2-a] pyridines

1, 2, 3-triazoles


Input: The present article reports the synthesis and anticonvulsant studies of new 2-arylimidazo [1, 2-a] pyridines carrying suitably substituted 1, 2, 3-triazoles as well as their intermediates.

2-arylimidazo [1, 2-a] pyridines

1, 2, 3-triazoles


Input: The structures of newly synthesized compounds were confirmed by various spectroscopic techniques.


Input: The anticonvulsant study was carried out by MES and scPTZ screening methods, while their toxicity study was performed following Rotarod method.


Input: The active compounds showed enhanced seizure control in scPTZ method when compared with that of MES method.


Input: Compounds 3f, 4c, 4f, 5k, 5p and 5w carrying active pharmacophores exhibited complete protection against seizure and their results were comparable with standard drug diazepam.

diazepam


Input: Majority of new compounds were found to be non-toxic, while few of them showed toxicity at 100mg/kg.


Input: The clogP values of target compounds are in the range of 3. 5-5. 3, which confirm their lipophilic nature.


Input: Synthesis, characterization and cytotoxic activity on breast cancer cells of new half-titanocene derivatives.

half-titanocene


Input: A series of novel titanocene-complexes has been prepared and evaluated for their growth regulatory effects in MCF7 and SkBr3 breast cancer cells.

titanocene


Input: The capability of some of these compound to elicit relevant repressive effects on cancer cell growth could be taken into account towards novel pharmacological approaches in cancer therapy.


Input: Octameric CENP-A Nucleosomes Are Present at Human Centromeres throughout the Cell Cycle.


Input: The presence of a single centromere on each chromosome that signals formation of a mitotic kinetochore is central to accurate chromosome segregation [1].


Input: The histone H3 variant centromere protein-A (CENP-A) is critical for centromere identity and function; CENP-A chromatin acts as an epigenetic mark to direct both centromere and kinetochore assembly [2-4].


Input: Interpreting the centromere epigenetic mark ensures propagation of a single centromere per chromosome to maintain ploidy.


Input: Thus, understanding the nature of CENP-A chromatin is crucial for all cell divisions.


Input: However, there are ongoing debates over the fundamental composition of centromeric chromatin.


Input: Here we show that natively assembled human CENP-A nucleosomes are octameric throughout the cell cycle.


Input: Using total internal reflection fluorescence (TIRF)-coupled photobleaching-assisted copy-number counting of single nucleosomes obtained from cultured cells, we find that the majority of CENP-A nucleosomes contain CENP-A dimers.


Input: In addition, we detect the presence of H2B and H4 in these nucleosomes.


Input: Surprisingly, CENP-A associated with the chaperone HJURP can exist as either monomer or dimer, indicating possible assembly intermediates.


Input: Thus, our findings indicate that octameric CENP-A nucleosomes mark the centromeric region to ensure proper epigenetic inheritance and kinetochore assembly.


Input: A comparative study of protein carbonylation and mitochondrial dysfunction using the neurotoxicants 1, 3-dinitrobenzene, 3-nitropropionic acid, and 3-chloropropanediol.

1, 3-dinitrobenzene

3-nitropropionic acid


Input: This comparative evaluation of neurotoxicants previously identified as models of chemical-induced mitochondrial dysfunction and energy deprivation demonstrated that subtoxic concentrations of 1, 3-dinitrobenzene (1, 3-DNB), 3-nitropropionic acid (3-NPA), and 3-chloropropanediol (3-CPD) each led to concentration-dependent loss of the mitochondrial membrane potential (Delta Psi m) associated with similar patterns of protein carbonylation.

1, 3-dinitrobenzene

1, 3-DNB

3-nitropropionic acid


Input: Subtoxic concentrations of each neurotoxicant were determined by measuring DI TNC1 cell viability using the MTS cell proliferation assay.


Input: Although exposure 1 mu M, 10 mu M, and 100 mu M concentrations of each toxicant did not result in loss of cell viability after 48h, exposure to each toxicant at these concentrations led to concentration-dependent loss of tetramethyl rhodamine methyl ester (TMRM) fluorescence over the same exposure period.

tetramethyl rhodamine methyl ester

TMRM


Input: Preincubation with the antioxidant, deferoxamine, was effective in preventing loss of TMRM flurorescence.

deferoxamine

TMRM


Input: Through the combined use of two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and Oxyblot analysis, this study demonstrated that exposure to each toxicant resulted in the formation of distinctly similar patterns of protein carbonylation comprised of specific proteins identified with tandem MS/MS.

polyacrylamide


Input: Our results provide insight as to how exposure to different neurotoxicants that enhance oxidative stress may, in fact, lead to mitochondrial injury and subsequent toxicity through selective, yet shared, pathways of protein modification by oxidative carbonylation.


Input: Adolescence methylphenidate treatment in a rodent model of attention deficit/hyperactivity disorder: Dopamine transporter function and cellular distribution in adulthood.

methylphenidate

Dopamine


Input: Attention deficit/hyperactivity disorder (ADHD) is attributed to dysfunction of the prefrontal cortex.


Input: Methylphenidate, an inhibitor of dopamine and norepinephrine transporters (DAT and NET, respectively), is a standard treatment for ADHD.

Methylphenidate

dopamine

norepinephrine


Input: The Spontaneously Hypertensive Rat (SHR) is a well-established animal model of ADHD.


Input: Our previous results showed that methylphenidate treatment in adolescent SHR enhanced cocaine self-administration during adulthood, and alterations in DAT function in prefrontal cortex play a role in this response.

methylphenidate

cocaine


Input: Importantly, prefrontal cortex subregions, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), have been shown to have distinct roles in ADHD and cocaine self-administration.

cocaine


Input: In the current study, SHR, Wistar-Kyoto (WKY) and Wistar (WIS) rats received a therapeutically relevant dose of methylphenidate (1. 5mg/kg, p. o.) or vehicle during adolescence and then OFC and mPFC DAT function and cellular expression were assessed during adulthood.

methylphenidate


Input: In both OFC and mPFC, no strain differences in Vmax or Km for dopamine uptake into synaptosomes were found between vehicle-treated SHR, WKY and WIS.

dopamine


Input: Methylphenidate increased DAT Vmax in SHR mPFC and decreased DAT Vmax in WKY OFC.

Methylphenidate


Input: Also, methylphenidate decreased DAT Km in WIS OFC.

methylphenidate


Input: Further, methylphenidate did not alter DAT cellular localization, indicating that methylphenidate treatment during adolescence regulated DAT function in SHR mPFC in a trafficking-independent manner.

methylphenidate

methylphenidate


Input: Thus, the increase in mPFC DAT function was an SHR-specific long term consequence of methylphenidate treatment during adolescence, which may be responsible for the treatment-induced alterations in behavior including the observed increases in cocaine self-administration.

methylphenidate

cocaine


Input: The effect of freeze-drying parameters and formulation composition on IgG stability during drying.


Input: The objective of this study was to explore the effects of freeze-drying parameters and formulation composition on polyclonal IgG stability during processing.


Input: Samples were freeze-dried with different primary drying pressures and secondary drying heating rates.


Input: After drying, changes in IgG in vitro binding activity, monomer recovery, average particle size, and polydispersity were studied from the rehydrated lyophilizates.


Input: Significant trends were not observed in binding activities or monomer recoveries, but increases in particle size and polydispersity were observed when using lower primary drying pressure.


Input: This effect could no longer be observed when sodium phosphate buffer was removed from the formulation.

sodium phosphate


Input: Altering the secondary drying heating rates did not result in any measurable changes in protein stability.


Input: Protective effects of Keemun black tea polysaccharides on acute carbon tetrachloride-caused oxidative hepatotoxicity in mice.

carbon tetrachloride


Input: This study was designed to investigate chemical characterization of the water-soluble polysaccharides extracted from Keemun black tea (KBTP), and their antioxidant and hepatoprotective effects against CCl4-induced oxidative damage in mice.


Input: HPLC analysis revealed that KBTP is the typical acidic heteropolysaccharides and consisted of nine monosaccharides.

monosaccharides


Input: Furthermore, KBTP showed highly ferric-reducing antioxidant power and scavenging effects against DPPH, OH and O2 (-) in vitro.

ferric

DPPH

OH

O2 (-)


Input: Administration of KBTP (200, 400 and 800mg/kgbw) in mice ahead of CCl4 injection could observably antagonize the CCl4-induced increases in serum ALT, AST, TG and TC, and the hepatic MDA and 8-iso-PGF2a levels, respectively.

MDA


Input: Mice with KBTP pretreatment displayed a better profile of hepatosomatic index and the improved GSH and SOD activities in comparison with CCl4-intoxicated mice.

GSH


Input: These biochemical results were further supported with liver histopathological assessment, revealing that KBTP has an observable prevention of liver damage induced by CCl4 in mice.


Input: Diagnosis and management of classical congenital adrenal hyperplasia.


Input: Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders.


Input: Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH.

steroid


Input: This disorder manifests with androgen excess with or without salt wasting.

androgen


Input: It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children.


Input: Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH.


Input: Genital surgery may be required for girls with CAH.


Input: Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis.


Input: In vitro assessment of cobalt oxide particle toxicity: Identifying and circumventing interference.

cobalt oxide


Input: The continuing development of nanotechnology necessitates the reliable assessment of potential adverse health consequences associated with human exposures.


Input: The physicochemical properties of nanomaterials can be responsible for unexpected interactions with components of classical toxicity assays, which may generate erroneous interpretations.


Input: In this paper, we describe how particle interference can be observed in in vitro toxicity tests (CellTiter Blue, CyQUANT, WST-1 and CellTiter-Glo assay) and in cell biology tests using flow cytometry (cell cycle analysis).


Input: We used cobalt oxide (Co3O4) particles as an example, but these assays can be performed, in principle, regardless of the nanoparticle considered.

cobalt oxide


Input: We have shown that cobalt particles interfere with most of these tests.

cobalt


Input: We adapted the protocol of the CellTiter-Glo assay to circumvent this interference and demonstrated that, using this protocol, the toxicity level is consistent with results obtained using the clonogenic assay, which is considered to be the reference test.


Input: Before assessing particle toxicity using in vitro toxicity tests, interference testing should be performed to avoid false interpretations.


Input: Furthermore, in some cases of interference, protocol adaptation can be considered to allow the reliable use of these quick and convenient in vitro tests.


Input: Opioids and their receptors: Are we there yet?


Input: Opioids have an important place in pharmacology.


Input: While their clinical use as analgesics is fundamental in medicine, their use is constrained by their side-effects and abuse potential.


Input: Pharmacologists have sought analgesics lacking side-effects and the abuse liability of the current agents.


Input: The identification of the opioid receptors in 1973 marked the beginning of our understanding of the molecular mechanisms of these agents.


Input: The isolation of the opioid peptides quickly followed, along with the classification of three families of opioid receptors.


Input: Clinicians have long been aware of subtle differences among the mu opioids that were not easily reconciled with a single receptor and selective antagonists implied two subdivisions of mu receptors.


Input: However, the cloning of the mu opioid receptor MOR-1 has led to the realization of the extensive complexity of the mu opioid receptor gene and its vast array of splice variants.


Input: Many of these splice variants are truncated and do not conform to the structure of traditional G-protein coupled receptors.


Input: Yet, evidence now shows that they are quite important and may prove valuable targets in the development of potent analgesics lacking the undesirable properties of current opioids.


Input: This article is part of a Special Issue entitled' NIDA 40th Anniversary Issue'


Input: Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.


Input: Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers.


Input: Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation.


Input: However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments.


Input: This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs.


Input: The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents.


Input: This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer.


Input: This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations.


Input: Polyglycerol coatings of glass vials for protein resistance.

Polyglycerol


Input: Proteins are surface active molecules which undergo non-specific adsorption when getting in contact with surfaces such as the primary packaging material.


Input: This process is critical as it may cause a loss of protein content or protein aggregation.


Input: To prevent unspecific adsorption, protein repellent coatings are of high interest.


Input: We describe the coating of industrial relevant borosilicate glass vials with linear methoxylated polyglycerol, hyperbranched polyglycerol, and hyperbranched methoxylated polyglycerol.

borosilicate

linear methoxylated polyglycerol

hyperbranched polyglycerol

hyperbranched methoxylated polyglycerol


Input: All coatings provide excellent protein repellent effects.


Input: The hyperbranched, non-methoxylated coating performed best.


Input: The protein repellent properties were maintained also after applying industrial relevant sterilization methods (<= 200 degrees C).


Input: Marginal differences in antibody stability between formulations stored in bare glass vials and coated vials were detected after 3months storage; the protein repellent effect remained largely stable.


Input: Here, we describe a new material suitable for the coating of primary packaging material of proteins which significantly reduces the protein adsorption and thus could present an interesting new possibility for biomedical applications.


Input: Inhibition of TGF-beta 1/Smad signal pathway is involved in the effect of Cordyceps sinensis against renal fibrosis in 5/6 nephrectomy rats.


Input: The present study aimed to investigate the effects of Cordyceps sinensis on renal fibrosis and its possible mechanisms.


Input: Sprague-Dawley rats were randomly divided into three groups: sham operation (SHAM) group, 5/6 subtotal nephrectomy (SNx) untreated group, and 5/6 subtotal nephrectomy treated with C. sinensis (2. 0g/kgd) (CS) group.


Input: Rats were studied 12weeks after the surgery, and the CS group presented with significantly lower proteinuria, and better renal function compared with the SNx group (p < 0. 05).


Input: Pathological study showed that the glomerulosclerosis tubulointerstitial injury score was significantly reduced in the CS group compared with the SNx group.


Input: Furthermore, the mRNA expression of TGF-beta 1, Smad2 and Smad3 and the protein expression of TGF-beta 1, T beta RI, T beta RII and p-Smad2/3 were attenuated by the C. sinensis treatment.