Input: Uniform single-crystalline quaternary sulphide nanoring photocatalysts are synthesized via the copper-ion-induced Kirkendall effect and is followed by a cation exchange reaction.

sulphide

copper


Input: The obtained Cu (2 +)-doped ZnIn2 S4 nanorings show highly preserved morphology, and demonstrate high visible-light-driven photocatalytic activity for H2 evolution in water splitting.

Cu (2 +)

ZnIn2 S4


Input: Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors.

serine


Input: Human and mouse marapsins (Prss27) are serine proteases preferentially expressed by stratified squamous epithelia.

serine


Input: However, mouse marapsin contains a transmembrane anchor absent from the human enzyme.


Input: To gain insights into physical forms, activities, inhibition, and roles in epithelial differentiation, we traced tail loss in human marapsin to a nonsense mutation in an ancestral ape, compared substrate preferences of mouse and human marapsins with those of the epithelial peptidase prostasin, designed a selective substrate and inhibitor, and generated Prss27-null mice.


Input: Phylogenetic analysis predicts that most marapsins are transmembrane proteins.


Input: However, nonsense mutations caused membrane anchor loss in three clades: human/bonobo/chimpanzee, guinea pig/degu/tuco-tuco/mole rat, and cattle/yak.


Input: Most marapsin-related proteases, including prostasins, are type I transmembrane proteins, but the closest relatives (prosemins) are not.


Input: Soluble mouse and human marapsins are tryptic with subsite preferences distinct from those of prostasin, lack general proteinase activity, and unlike prostasins resist antiproteases, including leupeptin, aprotinin, serpins, and alpha 2-macroglobulin, suggesting the presence of non-canonical active sites.


Input: Prss27-null mice develop normally in barrier conditions and are fertile without overt epithelial defects, indicating that marapsin does not play critical, non-redundant roles in development, reproduction, or epithelial differentiation.


Input: In conclusion, marapsins are conserved, inhibitor-resistant, tryptic peptidases.

tryptic


Input: Although marapsins are type I transmembrane proteins in their typical form, they mutated independently into anchorless forms in several mammalian clades, including one involving humans.


Input: Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors.

serine


Input: The need for better insulin therapy.


Input: Insulin replacement therapy corrects a core defect of diabetes pathophysiology.


Input: Since its introduction as a therapeutic modality almost 100 years ago, insulin therapy has undergone remarkable changes in purity and ability to provide more physiologic control of blood glucose levels.

glucose


Input: With glucose-lowering potential limited only by risks of hypoglycaemia, which remains the major limitation in our ability to achieve glycaemic goals, insulin replacement therapy remains a cornerstone of therapy.

glucose


Input: Major progress in reducing the risks of hypoglycemia has occurred with the development of insulin analogs.


Input: This review article briefly chronicles the evolution of insulin replacement strategies, highlighting both challenges in pharmaceutical development and patient acceptance, underscoring achievements, as well as denoting what improvements are still needed.


Input: Large enhancement of nonlinear optical response in a hybrid nanobiomaterial consisting of bacteriorhodopsin and cadmium telluride quantum dots.

cadmium telluride


Input: We report wavelength-dependent enormous enhancement of the nonlinear refractive index of wild-type bacteriorhodopsin in the presence of semiconductor quantum dots.


Input: The effect is strongest in the region just below the absorption edge of both constituents of this hybrid material and in samples that show strong F o rster resonance energy transfer.


Input: We show that enhancements of up to 4000% can be achieved by controlled engineering of the hybrid structure involving variations of the molar ratio of the constituents.


Input: This new hybrid material with exceptional nonlinear properties will have numerous photonic and optoelectronic applications employing its photochromic, energy transfer, and conversion properties.


Input: High-temperature and pressure-induced ferroelectricity in hydrogen-bonded supramolecular crystals of anilic acids and 2, 3-di (2-pyridinyl) pyrazine.

hydrogen

anilic acids

2, 3-di (2-pyridinyl) pyrazine


Input: Cocrystallization of anilic acids (H2xa) and 2, 3-di (2-pyridinyl) pyrazine (dppz) affords a variety of molecular geometries, including hydrogen-bonding and supramolecular structures.

anilic acids

2, 3-di (2-pyridinyl) pyrazine

dppz

hydrogen


Input: Proton-transferred 1: 1 salts of [H-dppz] [Hca] and [H-dppz] [Hba] (H2ca = chloranilic acid, H2ba = bromanilic acid) were found to host room-temperature ferroelectricity with a spontaneous polarization of 3-4 mu C/cm (2) along the hydrogen-bonded chains.

[H-dppz] [Hca]

[H-dppz] [Hba]

chloranilic acid

bromanilic acid

hydrogen


Input: Compared with the Curie points of other supramolecular ferroelectrics, those of the salts are relatively high (402 K and > 420 K, respectively) because of the elongated hydrogen bonds, which stabilize the proton-ordered state against thermal agitation.

hydrogen


Input: In addition to the ferroelectric black (alpha) form, dppz and H2ba gave two different crystal forms with a 2: 3 ratio: the brown beta form of [H (1. 5)-dppz] 2 [Hba] 3 and the brownish-red gamma form of [H-dppz] 2 [Hba] 2 [H2ba].

dppz

[H (1. 5)-dppz] 2 [Hba] 3

[H-dppz] 2 [Hba] 2 [H2ba]


Input: Mixed solutions of dppz with the less acidic fluoranilic acid (H2fa) exhibit valence instability; the H2fa molecules remain mostly neutral in absolute ethanol, whereas methanol (MeOH) solution apparently increases the deprotonated Hfa (-) content.

dppz

fluoranilic acid

ethanol

methanol

MeOH

Hfa (-)


Input: Crystallizations of these solutions gave a neutral [dppz] [H2fa] cocrystal and ionic [H-dppz (+)] [Hfa (-)]. MeOH salt, respectively.

[dppz] [H2fa]

[H-dppz (+)] [Hfa (-)]. MeOH


Input: The ferroelectricity induced by a modest hydrostatic pressure corroborates the conclusion that the ionic state with a dipolar [H-dppz (+)] [Hfa (-)] chain is energetically close to the nonpolar neutral ground state of the [dppz] [H2fa] crystal.

[H-dppz (+)] [Hfa (-)]

[dppz] [H2fa]


Input: Multiple targeted drugs carrying biodegradable membrane barrier: anti-adhesion, hemostasis, and anti-infection.


Input: A multiple targeted drug carrying bilayer membrane for preventing an abdominal adhesion is prepared by electrospinning.


Input: Two bioactive drugs were successfully incorporated into this bilayer membrane and can be independently released from nanofibrous scaffolds without losing structural integrity and functionality of the anti-adhesion membrane.


Input: Besides, the drug release profile could be easily adjusted by optimizing the swelling behavior of the fibrous scaffold.


Input: The inner layer of the bilayered fibrous membranes loaded with carbazochrome sodium sulfonate (CA) showed an excellent vascular hemostatic efficacy and formed little clot during in vivo experiment.

carbazochrome sodium sulfonate


Input: The outer layer loaded with tinidazole (TI) had outstanding antibacterial effect against the anaerobe.

tinidazole


Input: We believe this approach could serve as a model technique to guide the design of implants with drug delivery functions.


Input: Synthetically tractable click hydrogels for three-dimensional cell culture formed using tetrazine-norbornene chemistry.

tetrazine

norbornene


Input: The implementation of bio-orthogonal click chemistries is a topic of growing importance in the field of biomaterials, as it is enabling the development of increasingly complex hydrogel materials capable of providing dynamic, cell-instructive microenvironments.


Input: Here, we introduce the tetrazine-norbornene inverse electron demand Diels-Alder reaction as a new cross-linking chemistry for the formation of cell laden hydrogels.

tetrazine

norbornene


Input: The fast reaction rate and irreversible nature of this click reaction allowed for hydrogel formation within minutes when a multifunctional PEG-tetrazine macromer was reacted with a dinorbornene peptide.

PEG

tetrazine

dinorbornene


Input: In addition, the cytocompatibility of the polymerization led to high postencapsulation viability of human mesenchymal stem cells, and the specificity of the tetrazine-norbornene reaction was exploited for sequential modification of the network via thiol-ene photochemistry.

tetrazine

norbornene

thiol

ene


Input: These advantages, combined with the synthetic accessibility of the tetrazine molecule compared to other bio-orthogonal click reagents, make this cross-linking chemistry an interesting and powerful new tool for the development of cell-instructive hydrogels for tissue engineering applications.

tetrazine


Input: Extremely low-frequency magnetic field induces manganese accumulation in brain, kidney and liver of rats.

manganese


Input: The aim of the present study was to determine the effects of extremely low-frequency magnetic field (ELF-MF) on accumulation of manganese (Mn) in the kidney, liver and brain of rats.

manganese

Mn


Input: A total of 40 rats were randomly divided into eight groups.


Input: Four control groups received 0, 3. 75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively.

Mn


Input: The remaining four groups received same concentrations of Mn and were also exposed to ELF-MF (1. 5 mT; 50 Hz) for 4 h for 5 days a week during 45 days.

Mn


Input: Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma-optical emission spectrometer.

Mn


Input: In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups.

Mn

Mn


Input: Mn levels in brain, kidney and liver were also higher in Mn plus ELF-MF groups than in Mn groups.

Mn

Mn

Mn


Input: In conclusion, result of the current study showed that the ELF-MF induced manganese accumulation in kidney, liver and brain of rats.

manganese


Input: Acute respiratory distress syndrome due to exposure to high-concentration mixture of ethenone and crotonaldehyde.

ethenone

crotonaldehyde


Input: INTRODUCTION: Acute inhalational exposure leads to rapidly progressive acute respiratory distress syndrome (ARDS).


Input: This report is the first one to present a patient with ARDS in relation to long-standing exposure to a high-concentration mixture of ethenone and crotonaldehyde.

ethenone

crotonaldehyde


Input: Case report: A male worker in a chemical plant was accidentally exposed to the mixture of high-concentrated ethenone and crotonaldehyde for 5 min in an open space and worked continuously in the polluted area for approximately 12 h.

ethenone

crotonaldehyde


Input: On admission, he was conscious with the following vital parameters: blood pressure, 151/91 mmHg; pulse rate, 107 beats/min; respiratory rate, 30 breaths/min; temperature, 37. 6 degrees C; oxygen saturation, 92% supported by mask saturation 10 L/min; arterial blood gases showed P/F oxygen ratio of less than 200.

oxygen

oxygen


Input: Physical examination disclosed decreased bilateral vesicular sounds.


Input: A chest computed tomography revealed bilateral nonsegmental ground-glass opacities.


Input: The patient was mechanically ventilated and treated with corticosteroid.


Input: The patient was discharged without any symptoms.


Input: CONCLUSION: Exposure to mixtures of ethenone and crotonaldehyde can cause severe pulmonary injury leading to delayed ARDS.

ethenone

crotonaldehyde


Input: Influence of binder droplet dimension on granulation rate during fluidized bed granulation.


Input: Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process.


Input: Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone.

Lactose

hydroxypropyl

hydroxypropyl methyl

polyvinylpyrrolidone


Input: The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered.

lactose


Input: The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle.


Input: We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters.


Input: Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.

lactose

lactose


Input: Lasiodiplodin analogues from the endophytic fungus Sarocladium kiliense.

Lasiodiplodin


Input: A new 12-membered ring lactone, (3S), (6R)-6-hydroxylasiodiplodin (1), with two known analogues, (3R)-lasiodiplodin (2), and (3R), (5S)-5-hydroxylasiodiplodin (3) were isolated from the EtOH extracts of normal Apriona germari (Hope)-associated fungus Sarocladium kiliense grown in rice medium.

lactone

(3S), (6R)-6-hydroxylasiodiplodin

(3R), (5S)-5-hydroxylasiodiplodin

EtOH


Input: The structures of compounds 1-3 were elucidated by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction analysis, and modified Mosher' s method.


Input: Development of modified siRNA molecules incorporating 5-fluoro-2'-deoxyuridine residues to enhance cytotoxicity.


Input: Therapeutic small interfering RNAs (siRNAs) are composed of chemically modified nucleotides, which enhance RNA stability and increase affinity in Watson-Crick base pairing.


Input: However, the precise fate of such modified nucleotides once the siRNA is degraded within the cell is unknown.


Input: Previously, we demonstrated that deoxythymidine release from degraded siRNAs reversed the cytotoxicity of thymidylate synthase (TS)-targeted siRNAs and other TS inhibitor compounds.

deoxythymidine


Input: We hypothesized that siRNAs could be designed with specific nucleoside analogues that, once released, would enhance siRNA cytotoxicity.


Input: TS-targeted siRNAs were designed that contained 5-fluoro-2'-deoxyuridine (FdU) moieties at various locations within the siRNA.

FdU


Input: After transfection, these siRNAs suppressed TS protein and messenger RNA expression with different efficiencies depending on the location of the FdU modification.

FdU


Input: FdU was rapidly released from the siRNA as evidenced by formation of the covalent inhibitory ternary complex formed between TS protein and the FdU metabolite, FdUMP.

FdU

FdU

FdUMP


Input: These modified siRNAs exhibited 10-100-fold greater cytotoxicity and induced multiple DNA damage repair and apoptotic pathways when compared with control siRNAs.


Input: The strategy of designing siRNA molecules that incorporate cytotoxic nucleosides represents a potentially novel drug development approach for the treatment of cancer and other human diseases.


Input: A far-upstream (-70 kb) enhancer mediates Sox9 auto-regulation in somatic tissues during development and adult regeneration.


Input: SOX9 encodes a transcription factor that presides over the specification and differentiation of numerous progenitor and differentiated cell types, and although SOX9 haploinsufficiency and overexpression cause severe diseases in humans, including campomelic dysplasia, sex reversal and cancer, the mechanisms underlying SOX9 transcription remain largely unsolved.


Input: We identify here an evolutionarily conserved enhancer located 70-kb upstream of mouse Sox9 and call it SOM because it specifically activates a Sox9 promoter reporter in most Sox9-expressing somatic tissues in transgenic mice.


Input: Moreover, SOM-null fetuses and pups reduce Sox9 expression by 18-37% in the pancreas, lung, kidney, salivary gland, gut and liver.


Input: Weanlings exhibit half-size pancreatic islets and underproduce insulin and glucagon, and adults slowly recover from acute pancreatitis due to a 2-fold impairment in Sox9 upregulation.


Input: Molecular and genetic experiments reveal that Sox9 protein dimers bind to multiple recognition sites in the SOM sequence and are thereby both necessary and sufficient for enhancer activity.


Input: These findings thus uncover that Sox9 directly enhances its functions in somatic tissue development and adult regeneration through SOM-mediated positive auto-regulation.


Input: They provide thereby novel insights on molecular mechanisms controlling developmental and disease processes and suggest new strategies to improve disease treatments.


Input: Targeting pathological B cell receptor signalling in lymphoid malignancies.


Input: Signalling through the B cell receptor (BCR) is central to the development and maintenance of B cells.


Input: In light of the numerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co-opt this receptor to promote their own growth and survival.


Input: However, direct evidence for BCR signalling in human lymphoma has only come to light recently.


Input: Roles for antigen-dependent and antigen-independent, or tonic, BCR signalling have now been described for several different lymphoma subtypes.


Input: Furthermore, correlative data implicate antigen-dependent BCR signalling in many other forms of lymphoma.


Input: A host of therapeutic agents targeting effectors of the BCR signalling pathway are now in clinical trials and have shown initial success against multiple forms of lymphoma.


Input: MAP/microtubule affinity-regulating kinases, microtubule dynamics, and spermatogenesis.


Input: During spermatogenesis, spermatids derived from meiosis simultaneously undergo extensive morphological transformation, to become highly specialized and metabolically quiescent cells, and transport across the seminiferous epithelium.


Input: Spermatids are also transported back-and-forth across the seminiferous epithelium during the epithelial cycle until they line up at the luminal edge of the tubule to prepare for spermiation at stage VIII of the cycle.


Input: Spermatid transport thus requires the intricate coordination of the cytoskeletons in Sertoli cells (SCs) as spermatids are nonmotile cells lacking the ultrastructures of lamellipodia and filopodia, as well as the organized components of the cytoskeletons.


Input: In the course of preparing this brief review, we were surprised to see that, except for some earlier eminent morphological studies, little is known about the regulation of the microtubule (MT) cytoskeleton and the coordination of MT with the actin-based cytoskeleton to regulate spermatid transport during the epithelia cycle, illustrating that this is a largely neglected area of research in the field.


Input: Herein, we summarize recent findings in the field regarding the significance of actin-and tubulin-based cytoskeletons in SCs that support spermatid transport; we also highlight specific areas of research that deserve attention in future studies.


Input: Highly luminescent water-soluble quaternary Zn-Ag-In-S quantum dots for tumor cell-targeted imaging.

Zn

Ag

In

S


Input: Exploring the synthesis and biomedical applications of biocompatible quantum dots (QDs) is currently one of the fastest growing fields of nanotechnology.


Input: Hence, in this work, we present a facile approach to produce water-soluble (cadmium-free) quaternary Zn-Ag-In-S (ZAIS) QDs.

cadmium

Zn

Ag

In

S

ZAIS


Input: Their efficient photoluminescence (PL) emissions can be tuned widely in the range of 525-625 nm by controlling the size and composition of the QDs with the PL quantum yields (QYs) of 15-30%.


Input: These highly luminescent ZAIS QDs are less toxic due to the absence of highly toxic cadmium, and can be versatilely modified by a DHLA-PEG-based ligand.

ZAIS

cadmium

DHLA-PEG


Input: Importantly, after being modified by tumor cell-specific targeting ligands (e. g., folate and RGD peptide), the PEGylated quaternary QDs show potential applications in tumor cell imaging as a promising alternative for Cd-based QDs.

folate

Cd


Input: Enantiomeric separation of racemic 4-aryl-1, 4-dihydropyridines and 4-aryl-1, 2, 3, 4-tetrahydropyrimidines on a chiral tetraproline stationary phase.

4-aryl-1, 4-dihydropyridines

4-aryl-1, 2, 3, 4-tetrahydropyrimidines

tetraproline


Input: The chromatographic chiral resolution of 4-aryl-1, 4-dihydropyridines (1-32), 4-aryl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidines (33-38), and 4-aryl-2-oxo-1, 2, 3, 4-tetrahydropyrimidines (39-41) was studied on a tetraproline-immobilized chiral column synthesized in our lab.

4-aryl-1, 4-dihydropyridines

4-aryl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidines

4-aryl-2-oxo-1, 2, 3, 4-tetrahydropyrimidines

tetraproline


Input: This tetraproline chiral stationary phase can resolve most of these compounds.

tetraproline


Input: The 4-aryl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidines (33-38) and 4-aryl-2-oxo-1, 2, 3, 4-tetrahydropyrimidines (39-41) were more efficiently resolved than the racemic 4-aryl-1, 4-dihydropyridines on the tetraproline chiralstationary phase.

4-aryl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidines

4-aryl-2-oxo-1, 2, 3, 4-tetrahydropyrimidines

racemic 4-aryl-1, 4-dihydropyridines

tetraproline


Input: Analytes with 5, 5-dimethyl groups (39-41) were less efficiently resolved than analytes without 5, 5-dimethyl substituents (1-16).

5, 5-dimethyl

5, 5-dimethyl


Input: The 4-aryl-2-oxo-1, 2, 3, 4-tetrahydropyrimidines (39-41) without a sulfur atom were much more efficiently resolved than 4-aryl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidines (33-38).

4-aryl-2-oxo-1, 2, 3, 4-tetrahydropyrimidines

sulfur

4-aryl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidines


Input: No obvious electronic effects on the resolution of any of these analytes (1-41) were observed on the tetraproline chiral stationary phase.

tetraproline


Input: The tetraproline chiral stationary phase separated enantiomers mainly via hydrogen bonding interactions.

tetraproline

hydrogen


Input: Exfoliated graphitic carbon nitride nanosheets as efficient catalysts for hydrogen evolution under visible light.

graphitic carbon nitride

hydrogen


Input: Graphitic carbon nitride nanosheets are extracted, produced via simple liquid-phase exfoliation of a layered bulk material, g-C3 N4.

Graphitic carbon nitride

C3 N4


Input: The resulting nanosheets, having =~ 2 nm thickness and N/C atomic ratio of 1. 31, show an optical bandgap of 2. 65 eV.

N

C


Input: The carbon nitride nanosheets are demonstrated to exhibit excellent photocatalytic activity for hydrogen evolution under visible light.

carbon nitride

hydrogen


Input: Biological Design for Simultaneous Optical Transparency and Mechanical Robustness in the Shell of Placuna placenta.


Input: The flat circular-shaped shells from Placenta placenta demonstrate high optical transparency in the visible light range while still maintaining mechanical robustness.


Input: The optical and mechanical design of this mineralized material system in correlation to its multiscale structural and crystallographical features are discussed in detail through both experimental and theoretical approaches.


Input: Hierarchically Structured Nanotubes for Highly Efficient Dye-Sensitized Solar Cells.


Input: Hierarchical TiO2 nanotube arrays grown on Ti foil are yielded by subjecting electrochemically anodized, vertically oriented TiO2 nanotube arrays to hydrothermal processing.

Ti


Input: The resulting DSSCs exhibit a significantly enhanced power conversion efficiency of 7. 24%, which is a direct consequence of the synergy of higher dye loading, superior light-scattering ability, and fast electron transport.


Input: Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site.


Input: To discover promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4 (3H)-ones (QAOs) resulting in the identification of six molecules that reduced the Vmax of substrate hydrolysis without influencing the KM.

sulfated quinazolin-4 (3H)-ones

QAOs


Input: Mutagenesis of residues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition potency supporting recognition of an allosteric site.


Input: Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding.


Input: Competition with a positively charged, heparin-binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding.


Input: This discovery suggests the operation of a dual-element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch.


Input: The dual-element strategy may be widely applicable for discovering SAMs of other GBPs.


Input: A New Raman Spectroscopic Probe of Both the Protonation State and Noncovalent Interactions of Histidine Residues.


Input: The amino acid histidine (His) has a number of unique roles that can dictate function in proteins, and these roles are typically conferred through noncovalent interactions that depend on the protonation state of His' s 4-substituted imidazole ring.

amino acid histidine

His

His

4-substituted imidazole


Input: His' s protonation state can vary near physiological pH, and a probe of His' s variable protonation state and its resulting noncovalent interactions that has both high time resolution and no sample limitations could find wide use in determining the role of particular His residues in proteins.

His

His

His


Input: Here we use a classic deuterium exchange reaction to replace the C2-H hydrogen atom of the His imidazole ring with deuterium, leading to a unique aromatic C2-D stretching vibration whose frequency is sensitive to environmental changes across the entire imidazole ring.

deuterium

C2-H hydrogen

His imidazole

deuterium

imidazole


Input: Using nonresonant Raman spectroscopy, we demonstrate using model compounds that the frequency of this C2-D vibration shifts by 35 cm (-1) upon changes in the His protonation state.

His


Input: The C2-D band is a very weak infrared absorber, so this vibration is not expected to be useful in infrared transmission experiments for proteins.


Input: Solvent-dependent Raman experiments indicate that the C2-D band of the neutral imidazole ring is sensitive to H-bonding interaction with donors and acceptors of varying strengths, suggesting that the C2-D frequency can be used to identify H-bonding partners of specific His residues.

imidazole

H

H

His


Input: Raman spectra at varying concentrations of Cu (2 +) also show the C2-D band' s sensitivity to metal coordination, with differences due to changes in the coordination environment.

Cu (2 +)


Input: The strong Raman signal of this band and the sampling flexibility of Raman spectroscopy suggest that this vibration could be very useful in documenting the local role of His residues in many His-containing proteins and protein assemblies.

His

His


Input: Structural Investigation and Biological Activity of Sesquiterpene Lactones from the Traditional Chinese Herb Inula racemosa.

Sesquiterpene Lactones


Input: Five new sesquiterpene lactones, racemosalactones A-E (1-5), along with 19 known sesquiterpene latones (6-24), were isolated from the roots of Inula racemosa.

sesquiterpene lactones

racemosalactones A-E

sesquiterpene latones


Input: Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 2 was deduced from X-ray diffraction analysis.


Input: Compounds 1, 6, 8, 10, 12, 14, and 17 exhibited antiproliferative activities with IC50 values ranging from 0. 38 to 4. 19 mu g/mL against human non-small-cell lung cancer A549, hepatocellular carcinoma HepG2, and human fibrosarcoma HT1080 cells.


Input: Compounds 6 and 8 exhibited antiproliferative activities against endothelial cells with IC50 values of 2. 4 and 2. 5 mu g/mL, respectively.


Input: Furthermore, compounds 6 and 8 both inhibited endothelial cell tube formation at 1. 0 mu g/mL.


Input: A method for the rapid and straightforward preparative-scale isolation of compound 6 from alantolides is described.

alantolides


Input: Digitized charge transfer magnitude determined by metal-organic coordination number.


Input: Well-ordered metal-organic nanostructures of Fe-PTCDA (perylene-3, 4, 9, 10-tetracarboxylic-3, 4, 9, 10-dianhydride) chains and networks are grown on a Au (111) surface.

Fe-PTCDA

perylene-3, 4, 9, 10-tetracarboxylic-3, 4, 9, 10-dianhydride

Au


Input: These structures are investigated by high-resolution scanning tunneling microscopy.


Input: Digitized frontier orbital shifts are followed in scanning tunneling spectroscopy.


Input: By comparing the frontier energies with the molecular coordination environments, we conclude that the specific coordination affects the magnitude of charge transfer onto each PTCDA in the Fe-PTCDA hybridization system.

PTCDA

Fe-PTCDA


Input: A basic model is derived, which captures the essential underlying physics and correlates the observed energetic shift of the frontier orbital with the charge transfer.


Input: Cryptocapsinepoxide-Type Carotenoids from Red Mamey, Pouteria sapota.

Cryptocapsinepoxide


Input: New carotenoids, cryptocapsin-5, 6-epoxide, 3'-deoxycapsanthin-5, 6-epoxide, and cryptocapsin-5, 8-epoxides, have been isolated from the ripe fruits of red mamey (Pouteria sapota).

cryptocapsin-5, 6-epoxide

3'-deoxycapsanthin-5, 6-epoxide

cryptocapsin-5, 8-epoxides


Input: Cryptocapsin-5, 6-epoxide was prepared by partial synthesis via epoxidation of cryptocapsin, and the (5R, 6S)-and (5S, 6R)-stereoisomers were identified by HPLC-ECD analysis.

Cryptocapsin-5, 6-epoxide

cryptocapsin


Input: Spectroscopic data of the natural (anti) and semisynthetic (syn) derivatives obtained by acid-catalyzed rearrangement of cryptocapsin-5, 8-epoxide stereoisomers were compared for structural elucidation.

cryptocapsin-5, 8-epoxide


Input: Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin-5, 8-epoxides was performed, and HPLC-ECD analysis allowed configurational assignment of the separated stereoisomers.

cryptocapsin-5, 8-epoxides


Input: Efficient Pro-survival/angiogenic miRNA Delivery by an MRI-Detectable Nanomaterial.


Input: Herein, we report the use of biodegradable nanoparticles (NPs) containing perfluoro-1, 5-crown ether (PFCE), a fluorine-based compound (NP170-PFCE) with the capacity to track cells in vivo by magnetic ressonance imaging (MRI) and efficiently release miRNA.

perfluoro-1, 5-crown ether

PFCE

fluorine

PFCE


Input: NP170-PFCE complexed with miRNAs accumulate whitin the cell' s endolysosomal compartment and interact with higher frequency with argonaute2 (Ago2) and GW182 proteins, which are involved in the biological action of miRNAs, than commercial complexes formed by commercial reagents and miRNA, which in turn accumulate in the cell cytoplasm.

PFCE


Input: The release of miRNA132 (miR132) from the NPs increased 3-fold the survival of endothelial cells (ECs) transplanted in vivo and 3. 5-fold the blood perfusion in ischemic limbs relatively to control.


Input: Reversibly acetylated lysine residues play important roles in the enzymatic activity of Escherichia coli N-hydroxyarylamine O-acetyltransferase.

lysine

N-hydroxyarylamine O


Input: CobB is a bacterial NAD (+)-dependent protein deacetylase.

NAD (+)


Input: Although progress has been made in functional studies of this protein in recent years, its substrates and biological functions are still largely unclear.


Input: Using proteome microarray technology, potential substrates of Escherichia coli CobB were screened and nine proteins were identified, including N-hydroxyarylamine O-acetyltransferase (NhoA).

N-hydroxyarylamine O


Input: In vitro acetylation/deacetylation of NhoA was verified by western blotting and mass spectrometry, and two acetylated lysine residues were identified.

lysine


Input: Site-specific mutagenesis experiments showed that mutation of each acetylated lysine decreased the acetylation level of NhoA in vitro.

lysine


Input: Further analysis showed that variant NhoA proteins carrying substitutions at the two acetylated lysine residues are involved in both the O-acetyltransferase and N-acetyltransferase activity of NhoA.

lysine

O

N


Input: Structural analyses were also performed to explore the effects of the acetylated lysine residues on the activity of NhoA.

lysine


Input: These results suggest that reversible acetylation may play a role in the activity of Escherichia coli NhoA.


Input: Autoprocessing mechanism of severe acute respiratory syndrome coronavirus 3C-like protease (SARS-CoV 3CL (pro)) from its polyproteins.


Input: Like many other RNA viruses, severe acute respiratory syndrome coronavirus (SARS-CoV) produces polyproteins containing several non-structural proteins, which are then processed by the viral proteases.


Input: These proteases often exist within the polyproteins, and are excised by their own proteolytic activity (' autoprocessing').


Input: It is important to investigate the autoprocessing mechanism of these proteases from the point of view of anti-SARS-CoV drug design.


Input: In this paper, we describe a new method for investigating the autoprocessing mechanism of the main protease (M (pro)), which is also called the 3C-like protease (3CL (pro)).


Input: Using our method, we measured the activities, under the same conditions, of the mature form and pro-forms with the N-terminal pro-sequence, the C-terminal pro-sequence or both pro-sequences, toward the pro-form with both N-and C-terminal pro-sequences.

N

C

N

C


Input: The data indicate that the pro-forms of the enzyme have proteolytic activity, and are stimulated by the same proteolytic activity.


Input: The stimulation occurs in two steps, with approximately eightfold stimulation by N-terminal cleavage, approximately fourfold stimulation by C-terminal cleavage, and 23-fold stimulation by the cleavage of both termini, compared to the pro-form with both the N-and C-terminal pro-sequences.

N

C

N

C


Input: Such cleavage mainly occurs in a trans manner; i. e. the pro-form dimer cleaves the monomeric form.


Input: The stimulation by N-terminal pro-sequence removal is due to the cis (intra-dimer and inter-protomer) effect of formation of the new N-terminus, whereas that by C-terminal cleavage is due to removal of its trans (inter-dimer) inhibitory effect.

N

C


Input: A numerical simulation of the maturation pathway is presented.


Input: Computational design and biosensor applications of small molecule-sensing allosteric ribozymes.


Input: Here I describe accurate and time-efficient computational methods for designing small molecule-sensing allosteric ribozymes that serve as logic gates with NOT or YES Boolean logic functions.


Input: Theophylline-sensing ribozymes are engineered to have a high cleavage rate of 1. 3 min (-1) under physiologically relevant conditions.

Theophylline


Input: They are highly specific to theophylline and do not respond to caffeine, which differs in a single methyl group.

theophylline

caffeine

methyl


Input: These ribozymes are designed by fusing a theophylline aptamer with an extended version of the hammerhead ribozyme by modeling secondary structures.

theophylline


Input: Purine-sensing ribozymes are designed by fusing the minimal version of the hammerhead ribozyme with bacterial guanine or adenine aptamers by modeling 3D interactions.

Purine

guanine

adenine


Input: I have developed high-throughput compatible arrays based on purine RNA sensors that can be used for antibacterial drug discovery.

purine


Input: The ribozymes can be employed as molecular sensors in various applications, including exogenous control of gene expression, high-throughput screening arrays, and molecular computing.


Input: TDDFT studies on the determination of the absolute configurations and chiroptical properties of Strandberg-type polyoxometalates.


Input: The electronic circular dichroism (ECD) and UV-visible absorption (UV-vis) spectra of Strandberg-type polyoxometalates (POMs) (R, R)-[(R * PO3) 2M5O15] (2-) (R * = CH3CH (NH3), (M = Mo, W)) have been explored using the time-dependent density functional theory (TDDFT) method.

polyoxometalates

POMs

(R, R)-[(R * PO3) 2M5O15] (2-)

CH3CH (NH3)

Mo

W


Input: It demonstrates that the absolute configurations of chiral systems can be determined by chiroptical spectroscopic methods combined with DFT calculations.


Input: The calculated ECD spectra of the Strandberg-type molybdate were produced over the range of 3. 3-6. 5 eV, which are generally in agreement with the experimental spectra.


Input: In addition, the ECD spectra of (R, R)-[(R * PO3) 2W5O15] (2-) (R * = CH3CH (NH3)) were produced over the range of 4. 5-8. 5 eV.

(R, R)-[(R * PO3) 2W5O15] (2-)

CH3CH (NH3)


Input: The Becke' s half-and-half hybrid exchange-correlation functional (BHandHLYP) with the HF exchange fraction to 55% hybrid functional was found to well predict the excitation energies of studied systems.


Input: The origins of the ECD bands of two systems are mainly ascribed to charge-transfer (CT) transitions from oxygen atoms to metal atoms in polyanion.

oxygen


Input: The results suggest that the polyanion are chiroptical chromophores.


Input: The polyanion plays a role as an optically active chromophore and contribute to the absorptions of ECD spectra.


Input: The difference of the UV-vis/ECD spectra between two systems shows that the transition metal atom significantly influences on the chiroptical properties of the studied Strandberg-type POMs.

transition metal

POMs


Input: Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.


Input: Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER.


Input: We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice.


Input: Cloning of a short-period circadian mutant, Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation.

glycine

glutamate


Input: While loss of function of FBXL3 leads to period lengthening, mutation of Fbxl21 causes period shortening.


Input: FBXL21 forms an SCF E3 ligase complex that slowly degrades CRY in the cytoplasm but antagonizes the stronger E3 ligase activity of FBXL3 in the nucleus.


Input: FBXL21 plays a dual role: protecting CRY from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm.


Input: Thus, the balance and cellular compartmentalization of competing E3 ligases for CRY determine circadian period of the clock in mammals.


Input: Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus.

NMDA


Input: The activation of N-methyl-D-aspartate-receptors (NMDARs) in synapses provides plasticity and cell survival signals, whereas NMDARs residing in the neuronal membrane outside synapses trigger neurodegeneration.

N-methyl-D-aspartate


Input: At present, it is unclear how these opposing signals are transduced to and discriminated by the nucleus.


Input: In this study, we demonstrate that Jacob is a protein messenger that encodes the origin of synaptic versus extrasynaptic NMDAR signals and delivers them to the nucleus.


Input: Exclusively synaptic, but not extrasynaptic, NMDAR activation induces phosphorylation of Jacob at serine-180 by ERK1/2.

serine


Input: Long-distance trafficking of Jacob from synaptic, but not extrasynaptic, sites depends on ERK activity, and association with fragments of the intermediate filament alpha-internexin hinders dephosphorylation of the Jacob/ERK complex during nuclear transit.


Input: In the nucleus, the phosphorylation state of Jacob determines whether it induces cell death or promotes cell survival and enhances synaptic plasticity.


Input: Involvement of regucalcin in lipid metabolism and diabetes.


Input: Regucalcin (RGN/SMP30) was originally discovered in 1978 as a unique calcium-binding protein that does not contain the EF-hand motif of calcium-binding domain.

calcium

calcium


Input: The regucalcin gene (rgn) is localized on the X chromosome and is identified in over 15 species consisting the regucalcin family.


Input: Regucalcin has been shown to play a multifunctional role in cell regulation; maintaining of intracellular calcium homeostasis and suppressing of signal transduction, translational protein synthesis, nuclear deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, proliferation, and apoptosis in many cell types.

calcium


Input: Moreover, regucalcin may play a pathophysiological role in metabolic disorder.


Input: The expression of regucalcin is stimulated through the action of insulin in liver cells in vitro and in vivo and it is decreased in the liver of rats with type I diabetes induced by streptozotocin administration in vivo.

streptozotocin


Input: Overexpression of endogenous regucalcin stimulates glucose utilization and lipid production in liver cells with glucose supplementation in vitro.

glucose

glucose


Input: Regucalcin reveals insulin resistance in liver cells.


Input: Deficiency of regucalcin induces an impairment of glucose tolerance and lipid accumulation in the liver of mice in vivo.

glucose


Input: Overexpression of endogenous regucalcin has been shown to decrease triglyceride, total cholesterol and glycogen contents in the liver of rats, inducing hyperlipidemia.

triglyceride

cholesterol


Input: Leptin and adiponectin mRNA expressions in the liver tissues are decreased in regucalcin transgenic rats.


Input: Decrease in hepatic regucalcin is associated with the development and progression of nonalcoholic fatty liver disease and fibrosis in human patients.


Input: Regucalcin may be a key molecule in lipid metabolic disorder and diabetes.


Input: Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2'-C-methyl-6-O-methyl guanosine nucleoside and L-Alanine ester phosphoramidates.

2'-C-methyl-6-O-methyl guanosine nucleoside

L-Alanine ester phosphoramidates


Input: 7-Deazapurines are known to possess broad antiviral activity, however the 2'-C-methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus (HCV) replication.


Input: We previously reported the 6-O-methyl entity as a prodrug moiety to increase liphophilicity of guanine nucleosides and the ProTide approach applied to 2'-C-methyl-6-O-methylguanosine has lead to potent HCV inhibitors now in clinical trials.

guanine nucleosides


Input: In this Letter, we report the synthesis and biological evaluation of 2'-C-methyl-6-O-methyl-7-deaza guanosine and ProTide derivatives.

guanosine


Input: In contrast to prior studies, removal of the N-7 of the nucleobase entirely negates anti-HCV activity compared to the 2'-C-methyl-6-O-methylguanosine analogues.

N

nucleobase


Input: To understand better this significant loss of activity, enzymatic assays and molecular modeling were carried out and suggested 2'-C-methyl-6-O-methyl-7-deaza guanosine and related ProTides do not act as efficient prodrugs of the free nucleotide, in marked contrast to the case of the parent guanine analogue.

guanosine

nucleotide

guanine


Input: Discovery of 4-alkylamino-7-aryl-3-cyanoquinoline LRRK2 kinase inhibitors.


Input: Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial Parkinson' s disease (PD).

leucine


Input: The kinase activity of this complex protein is increased by pathogenic mutations.


Input: Inhibition of LRRK2 kinase activity has therefore emerged as a promising approach for the treatment of PD.


Input: Herein we report our findings on a series of 4-alkylamino-7-aryl-3-cyanoquinolines that exhibit kinase inhibitory activity against both wild type and G2019S mutant LRRK2.


Input: Activity was determined in both biochemical and cellular assays.


Input: Compound 14 was further evaluated in an in vivo pharmacodynamic study and found to significantly inhibit Ser935 phosphorylation after oral dosing.


Input: Protective effects of propolis on female rats' histopathological, biochemical and genotoxic changes during LPS induced endotoxemia.


Input: In recent years, propolis has been the object of extensive research for its antibacterial, antioxidant, anti-inflammatory, and antitumoral activities.


Input: This study aims to determine the hepatoprotective efficiency of propolis on experimental endotoxemia in rats.


Input: In the current study, fifty adult Sprague Dawley rats (weighing 200-300g) were randomly divided into five groups of ten rats each.


Input: Normal saline solution was administered to the rats in the control group, while in the second group LPS (30mg/kg), in the third group propolis (250mg/kg), in the fourth group first propolis and then LPS (30mg/kg), and in the fifth group, first LPS (30mg/kg) and then propolis were given.


Input: Six hours after the application, biochemical (MDA levels) and histopathological changes as well as global DNA methylation analysis in the liver tissue samples were determined, while in the blood tissue samples Genomic Template Stability (GTS,%) was evaluated using RAPD-PCR profiles.

MDA


Input: The results demonstrated that the administration of propolis could have a protective effect against changes of both genomic stability values and methylation profiles, and it minimized the increase in MDA and tissue damage caused by LPS.

MDA


Input: In conclusion, the application of propolis prior to LPS-induced endotoxemia has shown to reduce hepatic damage.


Input: Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (Delta Psi m) by Gentiana kurroo root extract.


Input: The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (Miapaca-2).


Input: The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays.

DPPH

hydroxyl


Input: The results were comparable to standard antioxidants like alpha-tocopherol, catechin and BHT used in such experiments.

alpha-tocopherol

catechin

BHT


Input: Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73 +/- 1. 02 and 46 +/- 2. 05mg/g extract respectively).

flavonoid


Input: The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (Miapaca-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1).

sulphorhodamine B

SRB


Input: G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner.


Input: The extract induced cell cycle arrest in Miapaca-2 cells at G0/G1 phase of the cell cycle.


Input: The population of apoptotic cells increased from 11. 4% in case of control to 49. 6% at 100 mu g/ml of G. kurroo root extract.


Input: The extract also induced a remarkable decrease in mitochondrial membrane potential (Delta Psi m) leading to apoptosis of cancer cells used.


Input: The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids.

iridoid glucosides

iridoids

secoiridoids

xanthones

flavonoids


Input: Iridoid glucosides are the bitter principles of Gentiana species.

Iridoid glucosides


Input: Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4''-O-beta-d-glucosyl-6'-O-(4-O-beta-d-glucosylcaffeoyl)-linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo.

Loganic acid

Sweroside

Swertiamarin

Gentiopicroside

Gentisin

Isogentisin

Gentioside

Norswertianolin

Swertianolin

4''-O-beta-d-glucosyl-6'-O-(4-O-beta-d-glucosylcaffeoyl)-linearoside

Swertisin

methanol


Input: Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals.


Input: The thyroid hormone (TH) system is involved in several important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo-regulation, osmo-regulation, and axis of regulation of other endocrine systems, sexual behaviour and fertility and cardiovascular function.


Input: Therefore, concern about TH disruption (THD) has resulted in strategies being developed to identify THD chemicals (THDCs).


Input: Information on potential of chemicals causing THD is typically derived from animal studies.


Input: For the majority of chemicals, however, this information is either limited or unavailable.


Input: It is also unlikely that animal experiments will be performed for all THD relevant chemicals in the near future for ethical, financial and practical reasons.


Input: In addition, typical animal experiments often do not provide information on the mechanism of action of THDC, making it harder to extrapolate results across species.


Input: Relevant effects may not be identified in animal studies when the effects are delayed, life stage specific, not assessed by the experimental paradigm (e. g., behaviour) or only occur when an organism has to adapt to environmental factors by modulating TH levels.


Input: Therefore, in vitro and in silico alternatives to identify THDC and quantify their potency are needed.


Input: THDC have many potential mechanisms of action, including altered hormone production, transport, metabolism, receptor activation and disruption of several feed-back mechanisms.


Input: In vitro assays are available for many of these endpoints, and the application of modern'-omics' technologies, applicable for in vivo studies can help to reveal relevant and possibly new endpoints for inclusion in a targeted THDC in vitro test battery.


Input: Within the framework of the ASAT initiative (Assuring Safety without Animal Testing), an international group consisting of experts in the areas of thyroid endocrinology, toxicology of endocrine disruption, neurotoxicology, high-throughput screening, computational biology, and regulatory affairs has reviewed the state of science for (1) known mechanisms for THD plus examples of THDC; (2) in vitro THD tests currently available or under development related to these mechanisms; and (3) in silico methods for estimating the blood levels of THDC.


Input: Based on this scientific review, the panel has recommended a battery of test methods to be able to classify chemicals as of less or high concern for further hazard and risk assessment for THD.


Input: In addition, research gaps and needs are identified to be able to optimize and validate the targeted THD in vitro test battery for a mechanism-based strategy for a decision to opt out or to proceed with further testing for THD.


Input: Impact of co-administration of protonated nanostructured aluminum silicate (cholesterol absorption inhibitor) on the absorption of lipid soluble vitamins D3 and K1: An assessment of pharmacokinetic and in vitro intraluminal processing.

aluminum silicate

cholesterol

vitamins D3 and K1


Input: Protonated nanostructured aluminum silicate (NSAS) is a protonated montmorillonite clay that was shown to be effective as an inhibitor of intestinal cholesterol absorption.

aluminum silicate

montmorillonite

cholesterol


Input: The effect of NSAS on the intestinal absorption of nutrients is unknown.


Input: An in vitro lipolysis model was adapted to test the intraluminal processing of vitamin D3 and K1 in the presence of various amounts of NSAS.

vitamin D3 and K1


Input: Additionally, vitamin absorption was assessed in male Sprague-Dawley rats randomized in the following treatment groups: IV administration of 0. 1mg/kg vitamin D3 and 1mg/kg vitamin K1, and a single-dose gavage of 1mg/kg vitamin D3 and 5mg/kg of vitamin K1 in peanut oil with various doses of NSAS slurry, 2% NSAS-fortified diet, or 50mg/kg stigmastanol.

vitamin D3

vitamin K1

vitamin D3

vitamin K1

stigmastanol


Input: The solubilized fraction of vitamin D3 in the lipolysis medium was reduced from 70% to 46% upon the addition of 120mg NSAS.

vitamin D3


Input: In contrast, the solubilized fractions of vitamin K1 were not significantly affected.

vitamin K1


Input: Although the NSAS-fortified diet did not significantly affect the absorbed fraction of both vitamins, NSAS slurry decreased the absorption of vitamin D3 as compared to the control.

vitamins

vitamin D3


Input: These results indicate that NSAS may be incorporated in diet to treat hypercholesterolemia; however, vitamin D3 monitoring may be required.

vitamin D3


Input: The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo.

zinc oxide


Input: The use of nanoparticulate zinc oxide (ZnO-NP) in sunscreens and other cosmetic products has raised public health concerns.

zinc oxide

ZnO


Input: The two key issues are the extent of exposure to ZnO-NP and the likely hazard after the application of ZnO-NP in sunscreen and cosmetic products to humans in vivo.

ZnO

ZnO


Input: Our aims were to assess exposure by the extent of ZnO-NP penetration into the viable epidermis and hazard by changes in the viable epidermal redox state for a number of topical products.

ZnO


Input: Of particular interest is the role of the particle coating, formulation used, and the presence of any enhancers.


Input: Multiphoton tomography with fluorescence lifetime imaging microscopy (MPT-FLIM) was used to simultaneously observe ZnO-NP penetration and potential metabolic changes within the viable epidermis of human volunteers after topical application of various ZnO-NP products.

ZnO

ZnO


Input: Coated and uncoated ZnO-NP remained in the superficial layers of the SC and in the skin furrows.

ZnO


Input: We observed limited penetration of coated ZnO-NP dispersed in a water-in-oil emulsion formulation, which was predominantly localized adjacent to the skin furrow.

ZnO


Input: However, the presence of ZnO-NP in the viable epidermis did not alter the metabolic state or morphology of the cells.

ZnO


Input: In summary, our data suggest that some limited penetration of coated and uncoated ZnO-NP may occur into viable stratum granulosum epidermis adjacent to furrows, but that the extent is not sufficient to affect the redox state of those viable cells.

ZnO


Input: Characteristics of indomethacin-saccharin (IMC-SAC) co-crystals prepared by an anti-solvent crystallization process.

indomethacin

saccharin

IMC

SAC


Input: The creation of co-crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance.


Input: In this study, co-crystal powders of indomethacin and saccharin (IMC-SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method.

indomethacin

saccharin

IMC

SAC


Input: No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported.


Input: Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC-SAC co-crystal powders by anti-solvent approach.

methanol

IMC

SAC


Input: The mechanism of a preferential formation of IMC-SAC co-crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept.

IMC

SAC

IMC


Input: Accordingly, the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties.


Input: Co-encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail.


Input: Co-encapsulation of drugs directed at commonly associated diseases provides a convenient means for administration, especially if transdermally delivered.


Input: In this work, a comprehensive study for the co-encapsulation of drugs with a differential lipophilicity, olanzapine and simvastatin, and their transdermal delivery in a formulation containing nanostructured lipid carriers (NLC) is presented.

olanzapine

simvastatin


Input: Focus is given to the evaluation of a strategy in which NLC and chemical permeation enhancers are combined.


Input: It comprises in vitro, in silico and cellular viability approaches.


Input: The optimization and rationalization of the systems are carried out using a two-step factorial design.


Input: It is shown that the external medium in the NLC dispersion strongly influences permeation.


Input: It is also seen that the use of NLC determines a synergistic effect with selected permeation enhancers, thus promoting marked flux enhancement ratios (48 and 21, respectively for olanzapine and simvastatin) relative to the drugs in solution.

olanzapine

simvastatin


Input: The developed formulations can be considered non-irritant.


Input: A correlation between enhancer positioning in a lipid bilayer, partially governed by a H-bonding phenomenon, and enhancement effect is suggested from molecular dynamics studies and experimental observations.

H


Input: Effect of protein malnutrition on the metabolism and toxicity of cisplatin, 5-fluorouracil and mitomycin C in rat stomach.

cisplatin

mitomycin C


Input: This study investigated the effect of protein malnutrition on metabolism and toxicity of cisplatin (CP), 5-fluorouracil (FU) and mitomycin C (MMC) in rat stomach.

cisplatin

mitomycin C

MMC


Input: Weanling male Wistar rats received a normal (24%) or low (2. 5%) protein diet for 28days and were allocated into: normally-fed control, protein-malnourished control (PM), 3 normally-fed drug-treated groups and 3 protein-malnourished drug-treated groups (PM-CP, PM-FU and PM-MMC).

MMC


Input: Cisplatin and MMC were injected intraperitoneally (8mg/kg on day 26 and 1mg/kg/day for 7days, respectively).

Cisplatin

MMC


Input: 5-Fluorouracil was given orally (50mg/kg/day for 5days).


Input: Compared with normally-fed counterparts, PM-CP rats exhibited higher glutathione S-transferase, aminopeptidase N and cysteine S-conjugate beta-lyase (CCBL) and lower gamma-glutamyltransferase activities, PM-FU rats exhibited decreased dihydropyrimidine dehydrogenase and cytochrome P450 1A1/2 activities and PM-MMC rats showed higher quinone reductase and depleted xanthine oxidase activities.

glutathione S

N

cysteine S

dihydropyrimidine

MMC

quinone

xanthine


Input: Protein-malnourished drug-treated groups exhibited exacerbated gastrotoxicity, relative to normally-fed counterparts, manifested by lower mucus levels, higher permeability and histopathological deterioration, along with increased oxidative stress in PM-CP rats and exaggerated prostaglandin E2 production in PM-MMC rats.

prostaglandin E2

MMC


Input: Conclusively, protein malnutrition alters CP, FU and MMC metabolism in rat stomach by enhancing CCBL pathway for CP activation, delaying FU elimination and activating two-electron reduction of MMC, potentiating their gastrotoxicity.

MMC

MMC


Input: Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells.

luteolin


Input: In this study, we investigated the anti-cancer effects of luteolin, a member of the flavonoid family, in NCI-H460 human lung carcinoma cells.

luteolin

flavonoid


Input: It was shown that luteolin induces apoptotic cell death through modulating both the extrinsic pathway and intrinsic pathways, which are suppressed by z-VAD-fmk, indicating that luteolin triggers caspase-dependant apoptosis.

luteolin

luteolin


Input: Furthermore, we found that the alpha subunit of the eukaryotic initiation factor 2 (eIF2 alpha/C/EBP homologous protein pathway, but not the c-Jun N-terminal kinase pathway, played a critical role in induction of apoptosis by luteolin.

N

luteolin


Input: The data indicated that luteolin also induces autophagy; evidence for this is the accumulation of microtubule-associated protein light chain-3 (LC3) II protein, the increase of LC3 puncta as well as an enhanced autophagy flux.

luteolin


Input: In addition, inhibiting autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that luteolin-induced autophagy functions as a cell death mechanism.

bafilomycin A1

luteolin


Input: Notably, the activated caspases that appeared with luteolin treatment cleaved Beclin-1, and the expression of LC3II remained the same even after cells were challenged with Beclin-1 siRNA, demonstrating that luteolin induces Beclin-1-independent autophagy.

luteolin

luteolin


Input: Taken together, our findings showed that luteolin triggers both endoplasmic reticulum stress-related apoptosis and non-canonical autophagy, which function as a cell death mechanism in NCI-H460 human lung cancer cells.

luteolin


Input: Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

Caffeic acid

adenine nucleotide


Input: This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation.

caffeic acid

nucleoside triphosphate

nucleotide

adenosine


Input: Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10mg/kg); IV (caffeic acid 50mg/kg); and V (caffeic acid 100mg/kg).

caffeic acid

caffeic acid

caffeic acid


Input: Animals were treated with caffeic acid diluted in oil for 30days.

caffeic acid


Input: In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P < 0. 05).

caffeic acid

ATP

ADP


Input: The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P < 0. 05).


Input: Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P < 0. 05).

Caffeic acid


Input: In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P < 0. 05).

caffeic acid


Input: These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system.

caffeic acid

caffeic acid


Input: Prediction and characterization of the linear IgE epitopes for the major soybean allergen beta-conglycinin using immunoinformatics tools.


Input: The alpha subunit of beta-conglycinin is a major allergen in soybean.


Input: The objective of this study was to predict and identify the linear immunoglobulin (Ig) E epitopes of the soybean alpha subunit of beta-conglycinin.


Input: Three immunoinformatics tools were used to predict the potential epitopes and were confirmed by dot-blot inhibition using sera from soybean allergic subjects.


Input: As a result, 15 peptides were predicted and assembled by solid-phase synthesis.


Input: Eleven epitopes were identified by the dot-blot inhibition test.


Input: Moreover, peptide 3 had IgE binding capability with all sera (5/5) tested, while peptide 1, 4, 6, 8 and12 could bind to 4/5 of the sera samples.


Input: Secondary structure prediction of peptide 3 and circular dichroism test validated that the structure of peptide 3 was a random coil.


Input: Cytotoxicity of aluminium oxide nanoparticles towards fresh water algal isolate at low exposure concentrations.

aluminium oxide


Input: The growing commercial applications had brought aluminium oxide nanoparticles under toxicologists' purview.

aluminium oxide


Input: In the present study, the cytotoxicity of two different sized aluminium oxide nanoparticles (ANP (1), mean hydrodynamic diameter 82. 6 +/- 22nm and ANP (2), mean hydrodynamic diameter 246. 9 +/- 39nm) towards freshwater algal isolate Chlorella ellipsoids at low exposure levels (<= 1 mu g/mL) using sterile lake water as the test medium was assessed.

aluminium oxide


Input: The dissolution of alumina nanoparticles and consequent contribution towards toxicity remained largely unexplored owing to its presumed insoluble nature.

alumina


Input: Herein, the leached Al (3 +) ion mediated toxicity has been studied along with direct particulate toxicity to bring out the dynamics of toxicity through colloidal stability, biochemical, spectroscopic and microscopic analyses.

Al (3 +)


Input: The mean hydrodynamic diameter increased with time both for ANP (1) [82. 6 +/- 22nm (0h) to 246. 3 +/- 59nm (24h), to 1204 +/- 140nm (72h)] and ANP (2) [246. 9 +/- 39nm (0h) to 368. 28 +/- 48nm (24h), to 1225. 96 +/- 186nm (72h)] signifying decreased relative abundance of submicron sized particles (< 1000nm).


Input: The detailed cytotoxicity assays showed a significant reduction in the viability dependent on dose and exposure.


Input: A significant increase in ROS and LDH levels were noted for both ANPs at 1 mu g/mL concentration.


Input: The zeta potential and FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells.


Input: The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (SEM, TEM, and CLSM).


Input: At 72h, significant Al (3 +) ion release in the test medium [0. 092 mu g/mL for ANP (1), and 0. 19 mu g/mL for ANP (2)] was noted, and the resulting suspension containing leached ions caused significant cytotoxicity, revealing a substantial ionic contribution.

Al (3 +)


Input: This study indicates that both the nano-size and ionic dissolution play a significant role in the cytotoxicity of ANPs towards freshwater algae, and the exposure period largely determines the prevalent mode of nano-toxicity.


Input: Food web analysis reveals effects of pH on mercury bioaccumulation at multiple trophic levels in streams.

mercury


Input: Biomagnification processes and the factors that govern them, including those for mercury (Hg), are poorly understood in streams.

mercury

Hg


Input: Total and methyl Hg concentrations and relative trophic position (using delta (15) N) were analyzed in biofilm and invertebrates from 21 streams in New Brunswick, Canada to assess food web biomagnification leading to the common minnow blacknose dace (Rhinichthys atratulus), a species known to have Hg concentrations that are higher in low pH waters.

methyl Hg

(15) N

Hg


Input: Biomagnification slopes within stream food webs measured using Hg vs. delta (15) N or corresponding trophic levels (TL) differed depending on the chemical species analyzed, with total Hg exhibiting increases of 1. 3-2. 5 per TL (mean slope of total Hg vs. delta (15) N = 0. 14 +/- 0. 06 S. D., range = 0. 06-0. 20) and methyl Hg showing a more pronounced increase of 2. 8 to 6. 0 per TL (mean slope of methyl Hg vs. delta (15) N = 0. 30 +/- 0. 08 S. D., range = 0. 22-0. 39).

Hg

(15) N

Hg

Hg

(15) N

methyl Hg

methyl Hg

(15) N


Input: While Hg biomagnification slopes through the entire food web (Trophic Magnification Factors, TMFs) were not influenced by water chemistry (pH), dietary concentrations of methyl Hg strongly influenced biomagnification factors (BMFs) for consumer-diet pairs within the food web at lower trophic levels, and BMFs between dace and predatory invertebrates were significantly higher in low pH waters.

Hg

methyl Hg


Input: These analyses, coupled with observations of higher Hg in primary producers in streams with low pH, suggest that pH influences both baseline concentrations and biomagnification of Hg in these systems.

Hg

Hg


Input: Because higher Hg concentrations in the diets of primary consumers and predatory insects in lower pH waters led to lower BMFs, these feeding groups showed insignificant relationships between Hg and pH; thus, altered BMFs associated with dietary concentrations can dampen the effects of environmental conditions on Hg concentrations.

Hg

Hg

Hg


Input: Light induced toxicity reduction of silver nanoparticles to Tetrahymena Pyriformis: Effect of particle size.

silver


Input: As a result of the extensive application of silver nanoparticles (AgNPs), their potential hazards, once they are released into the natural environment, are of great concern to people.

silver


Input: Since silver is very sensitive to light, the toxicity of AgNPs released into the natural environment will be inevitably affected by light.

silver


Input: The aim of this study was to investigate the relationship between light, toxicity, and particle size of AgNPs and deduce the possible mechanism of any interaction.


Input: Our study revealed that there was negative correlation between the particle size and the toxicity: small AgNPs (5-10nm) had higher toxicity than large AgNPs (15-25nm) to Tetrahymena pyriformis (T. pyriformis) under dark condition.


Input: Comparing the size dependent AgNPs toxicity under dark and light conditions, the effect of light to size dependent AgNPs toxicity was ascertained.


Input: The results indicated that AgNPs toxicity was decreased by light and the most important discovery was that the change of size dependent AgNPs toxicity had significant difference under light irradiation.


Input: The decrease of small AgNPs toxicity induced by light was more notable than large AgNPs.


Input: The decreased level of cell toxicity for small AgNPs was 32 +/- 0. 7%, whereas it was only 10. 6 +/- 5. 2% for large AgNPs kept 24h under light irradiation.


Input: The further investigation indicated that the above changes induced by light can be attributed to the decrease of released silver ions, particle growth and aggregation of AgNPs under light irradiation.

silver


Input: The obtained results showed that the light irradiation can promote the rapid growth of small AgNPs and result in the obvious increase of particle size and serious aggregation.


Input: These phenomena would induce the decrease of silver ions released from small AgNPs, which is responsible for the remarkable decrease of toxicity for small AgNPs.

silver


Input: Biodiversity of small molecules-a new perspective in screening set selection.


Input: How is the' diversity' of a compound set defined and how is the most appropriate compound subset identified for assay when screening the entire HTS deck is not an option?


Input: A common approach has so far been to cover as much of the chemical space as possible by screening a chemically diverse set of compounds.


Input: We show that, rather than chemical diversity, the biologic diversity of a compound library is an essential requirement for hit identification.


Input: We describe a simple and efficient approach for the design of a HTS library based on compound-target diversity.


Input: Biodiverse compound subsets outperform chemically diverse libraries regarding hit rate and the total number of unique chemical scaffolds present among hits.


Input: Specifically, by screening ~ 19% of a HTS collection, we expect to discover ~ 50-80% of all desired bioactive compounds.


Input: New quinazoline derivatives for telomeric G-quadruplex DNA: Effects of an added phenyl group on quadruplex binding ability.

quinazoline

phenyl


Input: To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [17].

indoloquinoline

benzofuroquinoline

quinazoline


Input: These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond.

hydrogen


Input: Studies showed that these quinazoline derivatives were effective and selective telomeric G-quadruplex ligands.

quinazoline


Input: With this encouragement, here we synthesized a series of N-(2-(quinazolin-2-yl) phenyl) benzamide (QPB) compounds as modified quinazoline derivatives.

N-(2-(quinazolin-2-yl) phenyl) benzamide

QPB

quinazoline


Input: In this modification, a phenyl group was introduced to the aromatic core.

phenyl


Input: The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G-quadruplex DNA than LZ-11, the most potential compound of reported quinazoline derivatives.

QPB

quinazoline


Input: Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied.

QPB


Input: Generation of intracellular reactive oxygen species and genotoxicity effect to exposure of nanosized polyamidoamine (PAMAM) dendrimers in PLHC-1 cells in vitro.

oxygen

polyamidoamine

PAMAM


Input: Polyamidoamine (PAMAM) dendrimers have previously been demonstrated to elicit systematically variable cyto-and eco-toxic responses, promising as the basis for structure-activity relationships governing nanotoxicological responses.

Polyamidoamine

PAMAM


Input: In this study, increased production of intracellular reactive oxygen species (ROS), genotoxicity and apoptosis due to in vitro exposure of fish hepatocellular carcinoma cells to dendrimer generations G4, G5 and G6 is demonstrated.

oxygen


Input: A PAMAM dendrimer generation dependent increase in ROS and genotoxicity was observed, consistent with our previous studies.

PAMAM


Input: The toxicological responses correlate well with the nanoparticle surface chemistry, specifically, the number of surface amino groups per generation.

amino


Input: Although ROS production initially increases approximately linearly, it saturates at higher doses.


Input: Notably, normalized to the molar dose of surface amino groups, the dose-dependent ROS production for different generations overlap exactly, indicating that the response is due to these functional units.

amino


Input: The genotoxicity response is also well correlated to the number of surface amino groups and therefore generation of PAMAM dendrimers.

amino

PAMAM


Input: The observed genotoxicity, related to DNA damage, is related to the generation and dose dependent production of intracellular ROS, at low levels.


Input: At the higher ROS levels, increased DNA damage is associated with the onset of necrosis.


Input: Tissue Distribution and Identification of Radioactivity Components at Elimination Phase after Oral Administration of [14C] CS-1036, an alpha-Amylase Inhibitor, to Rats.

[14C] CS-1036


Input: (2R, 3R, 4R)-4-hydroxy-2-(hydroxymethyl) pyrrolidin-3-yl 4-O-(6-deoxy-beta-D-glucopyranosyl)-alpha-D-glucopyranoside (CS-1036) is a potent inhibitor of pancreatic and salivary alpha-amylase.

(2R, 3R, 4R)-4-hydroxy-2-(hydroxymethyl) pyrrolidin-3-yl 4-O-(6-deoxy-beta-D-glucopyranosyl)-alpha-D-glucopyranoside


Input: After oral administration of [(14) C] CS-1036 to rats, the radioactivity was still detectable up to 7-14 days after administration in various tissues, and its terminal phase in plasma could be explained neither by the exposure of CS-1036 nor its major metabolite M1.

[(14) C] CS-1036


Input: The slow elimination of radioactivity in various tissues was hypothesized to be caused by covalent binding to macromolecules or use for biogenic components.


Input: To assess the use for biogenic components, amino acid analysis of plasma proteins and lipid analysis of adipose tissue were conducted after repeated oral administration of [(14) C] CS-1036 by high-performance liquid chromatography and accelerated mass spectrometry and by thin layer chromatography and liquid chromatography/mass spectrometry, respectively.

amino acid

[(14) C] CS-1036


Input: In amino acid analysis, glutamic acid, aspartic acid, alanine, and proline were identified as major radioactive amino acids, and radioactive nonessential amino acids occupied 76. 0% of the radioactivity.

amino acid

glutamic acid

aspartic acid

alanine

proline

amino acids

amino acids


Input: In lipid analysis, a part of the radioactive lipids were identified as the fatty acids constituting the neutral lipids by lipase-hydrolysis.

fatty acids


Input: The radioactive fatty acids from neutral lipids were identified as palmitic acid, oleic acid, and 8, 11, 14-eicosatrienoic acid.

fatty acids

palmitic acid

oleic acid

8, 11, 14-eicosatrienoic acid


Input: Intestinal flora were involved in CS-1036 metabolism and are indicated to be involved in the production of small molecule metabolites, which are the sources for amino acids and fatty acids, from [(14) C] CS-1036.

amino acids

fatty acids

[(14) C] CS-1036


Input: In conclusion, radioactivity derived from [(14) C] CS-1036 was incorporated as the constituents of amino acids of plasma proteins and fatty acids of neutral lipids.

[(14) C] CS-1036

amino acids

fatty acids


Input: Novel oleanolic vinyl boronates: Synthesis and antitumor activity.

oleanolic vinyl boronates


Input: A series of novel oleanane-type pentacyclic triterpenoids bearing a boronate ester moiety at C3 have been synthesized by palladium-catalyzed cross-coupling of bis (pinacolato) diboron with vinyl triflates, in the presence of base, and these compounds were fully characterized by 1D and 2D NMR techniques.

oleanane

triterpenoids

boronate ester

palladium

bis (pinacolato) diboron

vinyl triflates


Input: Evaluation of their antiproliferative effects on a panel of hematological-based and solid tumor cell lines identified three active oleanolic vinyl boronates that inhibited the growth of leukemia (Jurkat, K562), Burkitt' s lymphoma (Jijoye), cervix (Hela), colon (SW480), and ovary (SKOV-3) cancer cells without concomitant inhibition of non-tumoral human fibroblasts.

oleanolic vinyl boronates


Input: Their mechanisms of action were investigated on the leukemia Jurkat cell line.


Input: The results show that the incorporation of boron in the oleanolic acid core combined with the presence of amide bonds afforded compounds with desirable biological effects such as apoptosis induction and inhibition of proteasomal activity on tumor cells, which makes them potential templates for further development in the anticancer drug setting.

boron

oleanolic acid

amide


Input: Microwave-assisted synthesis of arene ruthenium (II) complexes that induce S-phase arrest in cancer cells by DNA damage-mediated p53 phosphorylation.

arene ruthenium (II)


Input: A series of arene ruthenium (II) complexes coordinated by phenanthroimidazole derivates, [(C6H6) Ru (L) Cl] Cl. 2H2O (1b L = IP, 2b L = p-NMe2PIP, 3b L = p-MeOPIP, 4b L = p-HOPIP, 5b L = p-COOHPIP, 6b L = p-CF3PIP, 7b L = p-BrPIP) have been synthesized in yields of 89-92% under microwave irradiation in 30 min, and the crystal structure of 1b by XRD gives a typical " piano stool " conformation.

arene ruthenium (II)

phenanthroimidazole

[(C6H6) Ru (L) Cl] Cl. 2H2O

p-MeOPIP

p-HOPIP

p-COOHPIP

p-BrPIP


Input: The antitumor activity of these complexes against various tumor cells have been evaluated by MTT assay, and the results show that this type of arene Ru (II) complexes exhibit acceptable inhibitory effect against all of these tumor cells, especially osteosarcoma MG-63 cells, but with low toxicity toward HK-2 human normal cells.

MTT

arene Ru (II)


Input: Studies on the mechanism revealed that cell cycle arrest at S-phase in MG-63 cells induced by the arene Ru (II) complex 2b, which was confirmed by the increase in the percentage of cells at S-phase and down-regulator of cyclin A.

arene Ru (II)


Input: The further studies by Comet assay at single cell level indicated that DNA damage in MG-63 cells was triggered by 2b, following with the up-regulation of phosphorylated p53 and histone.


Input: The studies by spectroscopy in vitro also indicate that 2b bind to DNA molecule by intercalative mode to disturb the bio-function of tumor cells.


Input: In conclusion, the synthetic arene Ru (II) complexes could serve as novel p53 activator with potential application in cancer chemotherapy.

arene Ru (II)


Input: Capping-agent-free synthesis of substrate-supported porous icosahedral gold nanoparticles.


Input: We report a new capping-agent-free strategy for the synthesis of substrate-supported porous icosahedral Au nanoparticles (NPs) with rough naked surfaces, based on the crystallization from substrate-supported thin solution layers followed by solid-phase thermolysis.

Au


Input: The plasmonic properties of icosahedral Au NPs have been studied using single particle dark-field scattering microscopy and spectroscopy.

Au


Input: The two distinct localized surface plasmon resonance (LSPR) bands observed in the single particle dark-field spectra can be ascribed to the quadrupole resonance at ca.


Input: 425 nm and the size-dependent dipole resonance in the red region (645-708 nm).


Input: The unique rough naked surface, the facile synthesis, together with the ability to control the nanoparticle size and to vary the LSPR frequency in the red region, would make the substrate-supported porous icosahedral Au NPs promising on multiple levels in the applications of catalysis, ultrasensitive biosensors, and in surface-enhanced Raman scattering (SERS).

Au


Input: Cerebrovascular Dilation via Selective Targeting of the Cholane Steroid-Recognition Site in the BK Channel beta 1-Subunit by a Novel Nonsteroidal Agent.

Cholane Steroid


Input: The Ca (2 +)/voltage-gated K (+) large conductance (BK) channel beta 1 subunit is particularly abundant in vascular smooth muscle.

Ca (2 +

K (+)


Input: By determining their phenotype, BK beta 1 allows the BK channels to reduce myogenic tone, facilitating vasodilation.


Input: The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK beta 1 site that includes Thr169.

steroid lithocholic acid

LCA


Input: Whether exogenous nonsteroidal agents can access this site to selectively activate beta 1-containing BK channels and evoke vasodilation remain unknown.


Input: We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA).

LCA

sodium 3-hydroxyolean-12-en-30-oate

HENA


Input: HENA activated the BK (cbv1 + beta 1) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 mu M) similar to and an efficacy (x 2. 5 potentiation) significantly greater than that of LCA.

HENA

LCA


Input: This HENA action was replicated on native channels in rat cerebral artery myocytes.

HENA


Input: HENA failed to activate the channels made of cbv1 + beta 2, beta 3, beta 4, or beta 1T169A, indicating that this drug selectively targets beta 1-containing BK channels via the BK beta 1 steroid-sensing site.

HENA

steroid


Input: HENA (3-45 mu M) dilated the rat and C57BL/6 mouse pressurized cerebral arteries.

HENA


Input: Consistent with the electrophysiologic results, this effect was larger than that of LCA.

LCA


Input: HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK beta 1' s role in HENA action.

HENA

HENA


Input: Finally, carotid artery-infusion of HENA (45 mu M) dilated the pial cerebral arterioles via selective BK-channel targeting.

HENA


Input: In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates beta 1-containing BK channels by targeting the steroid-sensing site in BK beta 1, rendering vasodilation.


Input: Contribution of the m1 transmembrane helix and pre-m1 region to positive allosteric modulation and gating of N-methyl-d-aspartate receptors.

N-methyl-d-aspartate


Input: N-methyl-d-aspartate (NMDA) receptors are glutamate-gated ion channels whose function is critical for normal excitatory synaptic transmission in the brain and whose dysfunction has been implicated in several neurologic conditions.

N-methyl-d-aspartate

NMDA


Input: NMDA receptor function is subject to extensive allosteric regulation both by endogenous compounds and by exogenous small molecules.

NMDA


Input: Elucidating the structural determinants and mechanism of action by which allosteric regulators control gating will enhance our understanding of NMDA receptor activation and facilitate the development of novel therapeutics.

NMDA


Input: Here, we investigated the structural determinants for (3-chlorophenyl) (6, 7-dimethoxy-1-((4-methoxyphenoxy) methyl)-3, 4-dihydroisoquinolin-2 (1H)-yl) methanone (CIQ), a GluN2C/2D-selective positive allosteric modulator.

(3-chlorophenyl) (6, 7-dimethoxy-1-((4-methoxyphenoxy) methyl)-3, 4-dihydroisoquinolin-2 (1H)-yl) methanone

CIQ


Input: We show that CIQ does not bind to the amino-terminal domain of the NMDA receptor and does not share structural determinants with modulators acting at the agonist-binding domain dimer interface or ion channel pore.

CIQ

amino

NMDA


Input: Rather, we identified critical determinants of CIQ modulation in the region near the first transmembrane helix of GluN2D, including in a putative pre-M1 cuff helix that may influence channel gating.

CIQ


Input: We also show that mutations within the GluN2D pre-M1 region alter open probability of the NMDA receptor.

NMDA


Input: These results suggest a novel site of action for potentiation of NMDA receptors by small molecules and implicate the pre-M1 region in NMDA receptor gating.

NMDA

NMDA


Input: Properties and self-assembled packing morphology of long alkyl-chained substituted polyhedral oligomeric silsesquioxanes (POSS) cages.

polyhedral oligomeric silsesquioxanes

POSS


Input: Polyhedral oligomeric silsesquioxane (POSS) cubic cage systems (octa-n-octadecyloctasilsesquioxane, (T8C18) and octakis (n-octadecyldimethylsiloxy) octasilsesquioxane, (Q8C18)) were synthesised with eight long n-alkyl chain (R = C18H37) substituent arms, as model nano-functionalized compounds.

Polyhedral oligomeric silsesquioxane

POSS

octa-n-octadecyloctasilsesquioxane

octakis (n-octadecyldimethylsiloxy) octasilsesquioxane


Input: The crystalline packing morphology of the cages was studied using time-resolved Small-and Wide-angle X-ray scattering (SAXS/WAXS), thermal and optical techniques.


Input: From thermal analysis the melting and crystallization temperatures of the Q8 cage were significantly less than those for the T8 cage.


Input: X-ray scattering showed that both cage systems have long-range crystalline ordering where the alkyl chains align in a parallel axial disposition from the POSS core giving a' rod-like' self-assembled packing morphology.


Input: The packing length-scale can be directly related to the overall dimensions of the POSS molecules.


Input: Compared to the T8 cages, the Q8 cages pack more efficiently allowing the interdigitation of the alkyl chain arms.


Input: Different packing modes and thermal behaviour observed for the T8 and Q8 cages is directly attributed to their structural chemistry.


Input: For the Q8 cage, the presence of the OSiMe2 spacer groups which tether the alkyl chain arms to the cage (absent in the T8 cages) allows greater flexibility of the arms letting them interdigitate with each other when packing which is not observed for the analogous T8 cages.


Input: Glycosylation of conotoxins.


Input: Conotoxins are small peptides present in the venom of cone snails.


Input: The snail uses this venom to paralyze and capture prey.


Input: The constituent conopeptides display a high level of chemical diversity and are of particular interest for scientists as tools employed in neurological studies and for drug development, because they target with exquisite specificity membrane receptors, transporters, and various ion channels in the nervous system.


Input: However, these peptides are known to contain a high frequency and variability of post-translational modifications-including sometimes O-glycosylation-which are of importance for biological activity.

O


Input: The potential application of specific conotoxins as neuropharmalogical agents and chemical probes requires a full characterization of the relevant peptides, including the structure of the carbohydrate part.

carbohydrate


Input: In this review, the currently existing knowledge of O-glycosylation of conotoxins is described.

O


Input: Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats.


Input: RATIONALE: Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin-releasing factor, the main mediator of the stress response.


Input: Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF).


Input: OBJECTIVES: In relation to the antistress properties of N/OFQ, we evaluated its effect on BE.


Input: After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N/OFQ was investigated after cycles of food restrictions.


Input: MATERIALS AND METHODS: In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction/refeeding and then stressed, or not stressed.


Input: In the other experiments, two groups were used: rats exposed or not to food restriction.


Input: RESULTS: Only restricted and stressed rats exhibited BE for HPF (containing chocolate cream).


Input: Intracerebroventricular injections of N/OFQ of 0. 5 nmol/rat significantly reduced BE.


Input: N/OFQ 1 nmol/rat did not reduce BE but significantly increased HPF intake following food restrictions.


Input: Cycles of food restriction increased animals' sensitivity to the hyperphagic effect of N/OFQ for HPF.


Input: In situ hybridization studies following food restrictions showed decreased ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN/OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively.


Input: CONCLUSIONS: These findings indicate that N/OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions.


Input: Neural substrates of acupuncture in the modulation of cravings induced by smoking-related visual cues: an FMRI study.


Input: RATIONALE: Cue reactivity is a key factor in modulating motivational and goal-directed behaviors associated with compulsive drug intake and relapse.


Input: Smoking-associated cues produce smoking urges and cravings and are accompanied by the activation of brain regions involved in attention, motivation, and reward.


Input: OBJECTIVES: We investigated whether acupuncture ameliorates cravings induced by smoking-related visual cues, and we explored the neural mechanisms underlying the effects of acupuncture on modulating smoking urges.


Input: METHODS: After 36 h of smoking abstinence, 25 right-handed male smokers underwent fMRI, during which smoking-related and neutral visual cues were presented.


Input: Twelve subjects were treated with real acupuncture (RA) at HT7 and 13 subjects received sham acupuncture (SA).


Input: During the scanning sessions, craving scores to smoking-related visual cues were assessed before and after RA or SA treatment.


Input: The differences in brain responses to smoking vs. neutral cues after treatment between the RA and SA groups were detected using three-way ANOVAs (Cue x Session x Group).


Input: RESULTS: After treatment, the craving scores were significantly decreased in the RA group, as compared to the SA group.


Input: When we explored the neural substrates of acupuncture on the modulation of cravings induced by smoking cues, significant differences were found in the medial prefrontal cortex, the premotor cortex, the amygdala, the hippocampus, and the thalamus.


Input: CONCLUSIONS: These findings suggest that acupuncture alleviates cue-induced cravings through the regulation of activity in brain regions involved in attention, motivation, and reward relative to craving scores in the initial abstinence phase.


Input: Impacts of spinosad and lambda-cyhalothrin on spider communities in cabbage fields in south Texas.

spinosad

lambda-cyhalothrin


Input: Spiders are a principal arthropod group that preys on numerous pests of vegetables and other crops.


Input: In this study, we determined the effects of the two most commonly used insecticides, spinosad and lambda-cyhalothrin, on diversity of spiders on cabbage in south Texas.

spinosad

lambda-cyhalothrin


Input: In two seasons (fall 2008 and spring 2009), we collected a total of 588 spiders belonging to 53 species in 11 families from spinosad and lambda-cyhalothrin-treated cabbages and the untreated control plants.

spinosad

lambda-cyhalothrin


Input: A great majority of spiders were collected from the pitfall traps (554) where only a few (34) were collected from the blower/vacuum sampling.


Input: In the insecticide-treated plots, there were significantly fewer spider individuals, species and families than in untreated fields.


Input: Spinosad had significantly less effect on spiders in total individuals, number of species and families than lambda-cyhalothrin.

Spinosad

lambda-cyhalothrin


Input: The effects of the two insecticides were further demonstrated by the Shannon-Weiner index (H') and the hierarchical richness index (HRI).


Input: Spider diversity in the spinosad-treated plots were not significantly different from that in the untreated fields but were greater than those in lambda-cyhalothrin-treated plots in both seasons when measured by H' values.

spinosad

lambda-cyhalothrin


Input: In contrast, the H' values of spider' s diversity in the lambda-cyhalothrin-treated plots were significantly lower than spinosad-treated and untreated plots.

lambda-cyhalothrin

spinosad


Input: High values of HRI for spider richness in the spinosad-treated plots suggested that spinosad had less effect on spiders than lambda-cyhalothrin.

spinosad

spinosad

lambda-cyhalothrin


Input: We concluded that spinosad was more compatible with spiders on cabbage compared to lambda-cyhalothrin and that this information should be used when developing insecticide resistance management strategies.

spinosad

lambda-cyhalothrin


Input: Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA.


Input: The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer' s disease and is by itself regulated by phosphorylation.


Input: We have used Nuclear Magnetic Resonance (NMR) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation.


Input: Detection and identification of phosphorylation on serine/threonine residues in a globular protein, while mostly occurring in solvent-exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein.

serine

threonine


Input: Other complications were encountered to characterize the extent of the phosphorylation, as part of the (1) H, (15) N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state.

(1) H

(15) N amide


Input: Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation.


Input: Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide.


Input: A reduced conformational heterogeneity and flexibility of the phospho-binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner.

phospho


Input: Additionally, a structural model of the phospho-WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho-S16 could compete with the phospho-substrate.

phospho

phosphate

phospho

phospho


Input: Combining NMR and small angle X-ray and neutron scattering in the structural analysis of a ternary protein-RNA complex.


Input: Many processes in the regulation of gene expression and signaling involve the formation of protein complexes involving multi-domain proteins.


Input: Individual domains that mediate protein-protein and protein-nucleic acid interactions are typically connected by flexible linkers, which contribute to conformational dynamics and enable the formation of complexes with distinct binding partners.


Input: Solution techniques are therefore required for structural analysis and to characterize potential conformational dynamics.


Input: Nuclear magnetic resonance spectroscopy (NMR) provides such information but often only sparse data are obtained with increasing molecular weight of the complexes.


Input: It is therefore beneficial to combine NMR data with additional structural restraints from complementary solution techniques.


Input: Small angle X-ray/neutron scattering (SAXS/SANS) data can be efficiently combined with NMR-derived information, either for validation or by providing additional restraints for structural analysis.