168 research outputs found
Antifungal compound honokiol triggers oxidative stress responsive signalling pathway and modulates central carbon metabolism
<p>The fast growing evidences have shown that the plant-derived compound honokiol is a promising candidate for treating multiple human diseases, such as inflammation and cancer. However, the mode-of-action (MoA) of honokiol remains largely unclear. Here, we studied the antifungal activity of honokiol in fission yeast model, with the goal of understanding the honokiol’s mechanism of action from the molecular level. We found that honokiol can inhibit the yeast growth at a dose-dependent way. Microarray analysis showed that honokiol has wide impacts on the fission yeast transcription levels (in total, 512 genes are up-regulated, and 42 genes are down-regulated). Gene set enrichment analysis indicated that over 45% up-regulated genes belong to the core environmental stress responses category. Moreover, network analysis suggested that there are extensive gene–gene interactions amongst the co-expression gene lists, which can assemble several biofunctionally important modules. It is noteworthy that several key components of central carbon metabolism, such as glucose transporters and metabolic enzymes of glycolysis, are involved in honokiol’s MoA. The complexity of the honokiol’s MoA displayed in previous studies and this work demonstrates that multiple omics approaches and bioinformatics tools should be applied together to achieve the complete scenario of honokiol’s antifungal function.</p
A Molecular Simulation Study of Carbon Dioxide Uptake by a Deep Eutectic Solvent Confined in Slit Nanopores
Molecular dynamics
simulations were performed to study the behavior
of CO<sub>2</sub> in varying amounts of a common deep eutectic solvent
(DES), choline chloride and ethylene glycol (termed ethaline), confined
in slit-like pores of width <i>H</i> = 5.2 nm with graphite
or rutile walls at <i>T</i> = 318 K. In the absence of DES,
CO<sub>2</sub> adsorbs to the pore walls, but increasing amounts of
ethaline inside the pores quickly displace carbon dioxide into the
gas/liquid interfaces, and into dissolution within the confined DES.
This process is driven by strong interactions of the ethaline components
with the pore walls, especially in the case of rutile systems, which
also cause the local ratio of choline chloride:ethylene glycol inside
the pores to depart from the bulk value of 1:2. As the amount of DES
inside the pores increases, the diffusivity of CO<sub>2</sub> reaches
a maximum in partially filled pores and decays to the values observed
in pores filled with DES, which are similar to the diffusion coefficients
of CO<sub>2</sub> in the bulk DES. The average number densities of
CO<sub>2</sub> near confined ethaline (i.e., dissolved in the DES,
and adsorbed at the pore walls and at the gas/liquid interface) are
significantly larger than the corresponding value observed in bulk
ethaline; for pores partially filled with DES, the overall average
number density of CO<sub>2</sub> can be ∼3.0–7.3 times
the value observed in bulk ethaline. Even though larger number densities
of CO<sub>2</sub> are observed in pores with no ethaline adsorbed,
our results suggest that systems of nanoporous materials partially
filled with DESs could be further explored and optimized for separation
of carbon dioxide and other gases, in analogy to the development of
supported ionic liquid phase materials for similar purposes
Synthesis, characterization and evaluation of tinidazole-loaded mPEG–PDLLA (10/90) <i>in situ</i> gel forming system for periodontitis treatment
<p>Traditional <i>in situ</i> gel forming systems are potential applications for parenteral administration but always accompanied with burst release. To overcome this limitation, the tinidazole (TNZ)-loaded <i>in situ</i> gel forming system using a diblock copolymer, monomethoxy poly(ethylene glycol)–block-poly(d,l-lactide) (mPEG–PDLLA), was designed. The formulation of the mPEG–PDLLA-based TNZ <i>in situ</i> gel forming system contained 5% (w/w) TNZ, 0.4% glycerol, 5 ml <i>N</i>-methyl pyrrolidone (NMP) and 35% (w/w) mPEG–PDLLA. The <i>in situ</i> gel forming system showed sustained TNZ release over 192 h with low burst effect (around 7% in the first 8 h) in the <i>in vitro</i> release study. Additionally, <i>in vivo</i> studies were performed on rabbits with ligature-induced periodontitis, and the concentration of TNZ in the gingival crevicular fluid (GCF) as well as the pharmacokinetic parameters was calculated and the pharmacological effect of TNZ-loaded <i>in situ</i> gel forming (mPEG–PDLLA)-based system was found effective. Finally, histological studies revealed that the gel was a safe formulation with low irritation. The desirable drug release kinetics combined with the excellent <i>in vivo</i> characteristics highlight the potential of the gel in the treatment of periodontitis. Therefore, these results confirmed that the TNZ-loaded <i>in situ</i> gel forming mPEG–PDLLA-based system could reduce burst release of TNZ and act as a sustained-release and injectable drug depot for periodontitis treatment.</p
Structural and Dynamical Properties of a Deep Eutectic Solvent Confined Inside a Slit Pore
We performed molecular dynamics (MD)
simulations to study the structure
and dynamics of the deep eutectic solvent (DES) choline iodide-glycerol
(CI.G) at a molar ratio of 1:3, inside slitlike titania [rutile (110)]
and graphitic nanopores of width <i>H = </i> 5.2 and 2.5
nm, and at a temperature <i>T = </i> 333 K. DESs share many
of the remarkable properties of ionic liquids (ILs) while being more
inexpensive; furthermore, and in addition to their fundamental scientific
interest, the systems modeled here are relevant to dye-sensitized
solar cells and gas separations. Our results show that glycerol can
form stable hydrogen bonds with the oxygen atoms in the rutile walls,
which account for ∼86% of the total number of hydrogen bonds
involving DES species (choline, iodide, and glycerol) in the first
layers (near the rutile walls), and for ∼24% of the total hydrogen
bonds observed for the DES inside a rutile pore of width <i>H
= </i> 5.2 nm. As a result, in these systems, the rutile walls
are coated by glycerol layers that are almost depleted of ions, have
a liquid structure that departs from that of the bulk DES, and have
very slow dynamics. In contrast, for DES inside graphitic pores, all
species are present in the first layers near the carbon walls, the
local liquid structure everywhere is similar to that of a bulk DES,
and the overall dynamics are faster than those observed inside rutile
pores of the same pore size; however, the DES species in the center
of both rutile and graphitic pores have comparable mobilities. When
the pore size is reduced, a larger proportion of the hydrogen bonds
involve the walls (in the case of a rutile pore), the overall dynamics
of the confined DES become slower, and in general the hydrogen bonds
formed are present during longer times in the simulation trajectories.
These observations are in general similar to the results obtained
by us for the IL [EMIM<sup>+</sup>]Â[TFMSI<sup>–</sup>] inside
the same rutile and graphitic pores; however, both of the IL ions
are present in the layers near the walls, and the ions in the center
of a rutile pore have dynamics that were 2–4 times slower than
those observed for the same ions in the center of a graphitic pore
Enhanced Akt-rpS6 activation and <i>in vitro</i> inhibition of rpS6 activation in Oo<i>Pten</i><sup>−/−</sup> oocytes by rapamycin.
<p>(<b>A</b>) Comparison of Akt-rpS6 signaling in Oo<i>Pten</i><sup>−/−</sup> and Oo<i>Pten</i><sup>+/+</sup> oocytes. Oocytes were isolated from ovaries of mice at postnatal day 12–14 and immunoblotting was performed as described in <i>Materials and Methods</i>. Loss of PTEN led to enhanced PI3K signaling as indicated by an increase in phosphorylated Akt (p-Akt). The level of phosphorylated rpS6 (p-rpS6) was also increased in Oo<i>Pten</i><sup>−/−</sup> oocytes compared with Oo<i>Pten</i><sup>+/+</sup> oocytes. Levels of total rpS6, Akt, and β-actin were used as internal controls. (<b>B</b>) Activation of rpS6 in Oo<i>Pten</i><sup>−/−</sup> oocytes is dependent on mTORC1 signaling. Oocytes were isolated from ovaries of Oo<i>Pten</i><sup>−/−</sup> mice at PD 12–14 as described in <i>Materials and Methods</i>. Treatment of oocytes with the mTORC1-specific inhibitor rapamycin (Rapa, 50 nM) for 2 h was found to largely suppress levels of phosphorylated rpS6 (p-rpS6), but did not affect the level of phosphorylated Akt (p-Akt). As a control, treatment of Oo<i>Pten</i><sup>−/−</sup> oocytes with the PI3K-specific inhibitor LY294002 (LY, 50 µM) for 2 h also largely suppressed levels of phosphorylated rpS6 (p-rpS6), but it also suppressed the level of phosphorylated Akt (p-Akt). This suggests that activation of rpS6 in Oo<i>Pten</i><sup>−/−</sup> oocytes is dependent on both PI3K and mTORC1 signaling. Levels of total Akt, rpS6, and β-actin were used as internal controls.</p
Preservation of the primordial follicle pool in Oo<i>Pten</i><sup>−/−</sup> ovaries by rapamycin treatment.
<p>(<b>A</b>) Prevention of the primordial follicle over-activation in Oo<i>Pten</i><sup>−/−</sup> mice by treatment with rapamycin. Rapamycin (5 mg/kg body weight) was injected daily into Oo<i>Pten</i><sup>−/−</sup> mice from postnatal day (PD) 4 to PD 22, and the ovaries were collected at PD 23 for morphological analysis. Ovaries from rapamycin-treated Oo<i>Pten</i><sup>−/−</sup> mice appeared smaller (c) than the ovaries from vehicle-treated Oo<i>Pten</i><sup>−/−</sup> mice (a). Scale bar = 50 µm. Clusters of primordial follicles were seen in rapamycin-treated Oo<i>Pten</i><sup>−/−</sup> mice at PD 23 (d, arrows) whereas all primordial follicles were activated in vehicle-treated Oo<i>Pten</i><sup>−/−</sup> mice at PD 23 (b, arrows). Scale bar = 50 µm. (<b>B</b>) Average numbers of total and primordial follicles in Oo<i>Pten</i><sup>+/+</sup>, Oo<i>Pten</i><sup>−/−</sup> (vehicle-treated), and Oo<i>Pten</i><sup>−/−</sup> (rapamycin-treated) ovaries at PD 23. Proportions of primordial follicles ± SEM (relative to the total number of follicles) are also shown. The proportion of primordial follicles in rapamycin-treated Oo<i>Pten</i><sup>−/−</sup> ovaries was 20±4.1%, which was smaller than the proportion in the Oo<i>Pten</i><sup>+/+</sup> ovaries (70±3.1%). Three mice were used for each experimental group. Rapa, rapamycin. (<b>C</b>) Comparison of the rpS6 and Akt phosphorylation levels in the ovaries of vehicle- and rapamycin-treated Oo<i>Pten</i><sup>−/−</sup> mice. Rapamycin (5 mg/kg body weight) was injected daily into Oo<i>Pten</i><sup>−/−</sup> mice from PD 4 to PD 22, the ovaries were collected at PD 23 and homogenized, and immunoblotting was performed as described in <i>Materials and Methods</i>. Rapamycin injection effectively suppressed the level of phosphorylated rpS6 (p-rpS6) without affecting the level of phosphorylated Akt (p-Akt) in the ovaries of Oo<i>Pten</i><sup>−/−</sup> mice. Levels of total rpS6, Akt, and β-actin were used as internal controls.</p
A Novel PbS Hierarchical Superstructure Guided by the Balance between Thermodynamic and Kinetic Control via a Single-Source Precursor Route
In this work, a novel lead sulfide (PbS) hierarchical
superstructure,
denoted as octapodal dendrites with a cubic center, has been synthesized
employing a simple single-source precursor route. Our experimental
results demonstrate that the novel hierarchical superstructure was
generated through the delicate balance between the kinetic growth
and thermodynamic growth regimes. Moreover, the morphology of PbS
crystals can be controlled by adjusting
the solvent under a thermodynamically or kinetically controlled growth
regime. It is highly expected that these findings will be useful in
understanding the formation of PbS nanocrystals with different morphologies,
which are also applicable to other face-centered cubic nanocrystals
Photoelectrochemical Water Splitting Systemî—¸A Study of Interfacial Charge Transfer with Scanning Electrochemical Microscopy
Fast charge transfer kinetics at
the photoelectrode/electrolyte interface is critical for efficient
photoelectrochemical (PEC) water splitting system. Thus, far, a measurement
of kinetics constants for such processes is limited. In this study,
scanning electrochemical microscopy (SECM) is employed to investigate
the charge transfer kinetics at the photoelectrode/electrolyte interface
in the feedback mode in order to simulate the oxygen evolution process
in PEC system. The popular photocatalysts BiVO<sub>4</sub> and Mo
doped BiVO<sub>4</sub> (labeled as Mo:BiVO<sub>4</sub>) are selected
as photoanodes and the common redox couple [FeÂ(CN)<sub>6</sub>]<sup>3–</sup>/[FeÂ(CN)<sub>6</sub>]<sup>4–</sup> as molecular
probe. SECM characterization can directly reveal the surface catalytic
reaction kinetics constant of 9.30 × 10<sup>7</sup> mol<sup>–1</sup> cm<sup>3</sup> s<sup>–1</sup> for the BiVO<sub>4</sub>. Furthermore,
we find that after excitation, the ratio of rate constant for photogenerated
hole to electron via Mo:BiVO<sub>4</sub> reacting with mediator at
the electrode/electrolyte interface is about 30 times larger than
that of BiVO<sub>4</sub>. This suggests that introduction of Mo<sup>6+</sup> ion into BiVO<sub>4</sub> can possibly facilitate solar
to oxygen evolution (hole involved process) and suppress the interfacial
back reaction (electron involved process) at photoanode/electrolyte
interface. Therefore, the SECM measurement allows us to make a comprehensive
analysis of interfacial charge transfer kinetics in PEC system
Synthesis, physicochemical properties and ocular pharmacokinetics of thermosensitive <i>in situ</i> hydrogels for ganciclovir in cytomegalovirus retinitis treatment
<p>Ganciclovir (GCV) is one of the most widely used antiviral drugs for the treatment of cytomegalovirus (CMV) retinitis. In this context, the aim of this study was to design <i>in situ</i> thermosensitive hydrogels for GCV ocular delivery by intravitreal injection to achieve sustained drug release behavior and improved ocular bioavailability in the treatment of CMV retinitis. A thermosensitive poly-(β-butyrolactone-co-lactic acid)-polyethylene glycol-poly (β-butyrolactone-co-lactic acid) (PBLA-PEG-PBLA) triblock copolymer was synthesized by ring-opening polymerization and characterization. The GCV-loaded PBLA-PEG-PBLA <i>in situ</i> hydrogels (15%, <i>w/w</i>) were then prepared with drug concentration at 2 mg·mL<sup>−1</sup> and the gelation temperatures, rheological properties, <i>in vitro</i> degradation and syringeability of <i>in situ</i> hydrogels for intravitreal injection were also investigated. Membraneless dissolution model was used to explore drug release behavior of PBLA-PEG-PBLA <i>in situ</i> hydrogel. The results indicated that more than 45 and 85% of GCV can be released within 24 and 96 h, respectively, which was verified by a non-Fickian diffusion mechanism. <i>In vivo</i> ocular pharmacokinetics study showed that area under drug-time curve (AUC) and half-life of PBLA-PEG-PBLA <i>in situ</i> hydrogel was higher (AUC was 61.80 μg·mL<sup>−1</sup>·h (<i>p</i> < .01) and <i>t</i><sub>1/2</sub> was 10.29 h in aqueous humor; AUC was 1008.66 μg·mL<sup>−1</sup>·h (<i>p</i> < .01) and <i>t</i><sub>1/2</sub> was 13.26 h (<i>p</i> < .01) in vitreous) than GCV injection with extended therapeutic activity. Based on obtained results, it was concluded that the thermosenstive PBLA-PEG-PBLA <i>in situ</i> hydrogel is a promising carrier of GCV for intravitreal injection.</p
Generating Huge Magnetocurrent by Using Spin-Dependent Dehydrogenation Based on Electrochemical System
Systems
featuring large magnetocurrent (MC) at room temperature
are attractive owing to their potential for application in magnetic
field sensing. Usually, the magnetic materials are exploited to achieve
large MC effect. Here, we report a huge MC of up to 150% in a nonmagnetic
system based on the electrochemical oxidation of hydrazine at room
temperature. The huge MC is ascribed to the spin-dependent N–H
bond cleavage and reformation through dehydrogenation during the oxidation
of hydrazine. Specifically, the N–H bond cleavage generates
singlet radical pairs. An external magnetic field can accelerate the
spin evolution from singlet to triplet in spin-correlated radical
pairs by perturbing spin precessions. Increasing the amount of triplet
radical pairs can largely reduce the N–H bond recovery and
significantly enhance the oxidation current of hydrazine. As a consequence,
the spin-dependent bond formation through dehydrogenation can provide
a new approach to generate huge MC in electrochemical cells
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