A Novel Etomidate Analog EL-0052 Retains Potent Hypnotic Effect and Stable Hemodynamics without Suppressing Adrenocortical Function.

Etomidate is a potent and rapidly acting anesthetic with high therapeutic index (TI) and superior hemodynamic stability. However, side effect of suppressing adrenocortical function limits its clinical use. To overcome this side effect, we designed a novel etomidate analog, EL-0052, aiming to retain beneficial properties of etomidate and avoid its disadvantage of suppressing adrenocortical steroid synthesis. Results exhibited that EL-0052 enhanced GABAA receptors currents with a concentration for EC50 of 0.98 ± 0.02 µM, which was about three times more potent than etomidate (3.07 ± 1.67 µM). Similar to hypnotic potency of etomidate, EL-0052 exhibited loss of righting reflex with ED50s of 1.02 (0.93-1.20) mg/kg in rats and 0.5 (0.45-0.56) mg/kg in dogs. The TI of EL-0052 in rats was 28, which was higher than 22 of etomidate. There was no significant difference in hypnotic onset time, recovery time, and walking time between EL-0052 and etomidate in rats. Both of them had minor effects on mean arterial pressure in dogs. EL-0052 had no significant effect on adrenocortical function in dogs even at a high dose (4.3 × ED50), whereas etomidate significantly inhibited corticosteroid secretion. The inhibition of cortisol synthesis assay showed that EL-0052 had a weak inhibition on cortisol biosynthesis in human H259 cells with an IC50 of 1050 ± 100 nM, which was 2.09 ± 0.27 nM for etomidate. EL-0052 retains the favorable properties of etomidate, including potent hypnotic effect, rapid onset and recovery, stable hemodynamics, and high therapeutic index without suppression of adrenocortical function. SIGNIFICANCE STATEMENT: The novel etomidate analog EL-0052 retains the favorable properties of etomidate without suppressing adrenocortical function and provides a new strategy to optimize the structure of etomidate.

n-decane diffusion in carbon nanotubes with vibration.

Carbon nanotubes (CNTs) have a wide range of applications in nanotechnology engineering. This research aims to quantify the effect of wall vibration on n-decane molecules' diffusion in double-walled CNTs (DWNTs) with different diameters and determine the diffusion mechanisms behind it. Molecular dynamics simulations are performed to generate mass density profiles of confined n-decane molecules. The root mean square fluctuation and mean squared displacement analyses show that the confinement suppresses n-decane molecules' fluctuations. A self-diffusion coefficient of n-decane molecules in a 13.6 Å-diameter DWNT is the largest. However, the vibration enhancement of the n-decane molecules' diffusion in a 27.1 Å-diameter DWNT is 207%, more extensive than that in 13.6 Å-diameter and 10.8 Å-diameter DWNTs. The n-decane-CNT attractive interactions, extreme confinement, and surface friction affect the n-decane molecules' diffusion in CNTs with vibration.

Wettability effect on nanoconfined water flow.

Understanding and controlling the flow of water confined in nanopores has tremendous implications in theoretical studies and industrial applications. Here, we propose a simple model for the confined water flow based on the concept of effective slip, which is a linear sum of true slip, depending on a contact angle, and apparent slip, caused by a spatial variation of the confined water viscosity as a function of wettability as well as the nanopore dimension. Results from this model show that the flow capacity of confined water is 10-1∼107 times that calculated by the no-slip Hagen-Poiseuille equation for nanopores with various contact angles and dimensions, in agreement with the majority of 53 different study cases from the literature. This work further sheds light on a controversy over an increase or decrease in flow capacity from molecular dynamics simulations and experiments.

Ultrahigh Water Flow Enhancement by Optimizing Nanopore Chemistry and Geometry.

The high permeability of nanoporous membranes is crucial for separation processes and energy conversions, especially for the world today that is facing growing water scarcity and energy demands. Unfortunately, further improving permeability, without sacrificing the required selectivity for specific applications, is still extremely challenging. Here, we shed light on the mechanisms of extremely high water permeability of artificial nanopores with the aquaporin-inspired pore geometry and propose a simple yet practical optimization strategy by using computational research to relate nanopore chemistry and geometry to permeability performance. We demonstrated that an ultrahigh water flow enhancement, up to 7 orders of magnitude, can be achieved by optimizing the combination of chemical and geometrical parameters of bioinspired artificial nanopores. Moreover, we addressed an existing debate over the water flow enhancement spanning over 10-1 to 105, attributed to the huge differences in chemical and geometrical properties. Our work provides a guideline to the design and optimization of nanofluidic devices with excellent performance.

Manipulating the Flow of Nanoconfined Water by Temperature Stimulation.

The manipulation of a nanoconfined fluid flow is a great challenge and is critical in both fundamental research and practical applications. Compared with chemical or biochemical stimulation, the use of temperature as controllable, physical stimulation possesses huge advantages, such as low cost, easy operation, reversibility, and no contamination. We demonstrate an elegant, simple strategy by which temperature stimulation can readily manipulate the nanoconfined water flow by tuning interfacial and viscous resistances. We show that with an increase in temperature, the water fluidity is decreased in hydrophilic nanopores, whereas it is enhanced by at least four orders of magnitude in hydrophobic nanopores, especially in carbon nanotubes with a controlled size and atomically smooth walls. We attribute these opposing trends to a dramatic difference in varying surface wettability that results from a small temperature variation.

Quinoline-based two-photon fluorescent probe for nitric oxide in live cells and tissues.

A two-photon fluorescent probe (QNO) for nitric oxide is reported. The probe is designed with a photoinduced electron transfer (PeT) mechanism and shows 12-fold fluorescence enhancement toward NO. Adopting a quinoline derivative as the fluorophore, QNO has a large two-photon action cross section value of 52 GM and long-wavelength emission. It also features high selectivity, low cytotoxicity, and pH insensitivity. By utilizing two-photon microscopy (TPM), QNO can detect NO in live cells and live tissues at a depth of 90-180 µm.

Highly sensitive quinoline-based two-photon fluorescent probe for monitoring intracellular free zinc ions.

Zn(2+) plays vital roles in regulating physiological and pathological processes. A number of diseases are associated with the disruption of intracellular free Zn(2+) homeostasis, and the relationship is still uncovered. Thus, it is important to monitor intracellular free Zn(2+) ions in real time, which is still challenging due to the low content of intracellular free Zn(2+). In this work, we report on the design and synthesis of a new two-photon (2P) fluorescent probe, QZn, based on quinoline derivative for intracellular free Zn(2+). Theoretical calculations were carried out to rationalize the design. The probe displayed a moderate 2P action cross section value of 51 GM at 820 nm and up to 10-fold fluorescence enhancement upon Zn(2+) binding. The detection limit of Zn(2+) was 15.1 pM, which presented a pronounced sensitivity toward Zn(2+) and indicated that QZn would be competent for detecting the low-content intracellular Zn(2+). By using two-photon microscopy, QZn was capable of monitoring the fluctuation of intracellular free zinc ions in real time.

Astragalus polysaccharide improves the growth, meat quality, antioxidant capacity and bacterial resistance of Furong crucian carp (Furong carp♀ × red crucian carp♂).

To evaluate the functional effects of APS (Astragalus polysaccharide) on Furong crucian carp, APS-supplemented diets (0.00 %, 0.05 %, 0.10 % and 0.15 %) were prepared and utilized in feeding experiment. The results showed that the 0.05 % APS group has the highest weight gain rate and specific growth rate, and the lowest feed coefficient rate. In addition, 0.05 % APS supplement could improve muscle elasticity, adhesiveness and chewiness. Moreover, the 0.15 % APS group had the highest spleen-somatic index and the 0.05 % group had the maximum intestinal villus length. 0.05 % and 0.10 % APS addition significantly increased T-AOC and CAT activities while MDA contents decreased in all APS groups. The plasma TNF-α levels in all APS groups significantly increased (P<0.05), and the 0.05 % group showed the highest TNF-α level in spleen. In APS addition groups, the tlr8, lgp2 and mda5 gene expressions were significantly elevated, while xbp1, caspase-2 and caspase-9 expressions decreased in uninfected and A. hydrophila-infected fish. Finally, higher survival rate and slower disease outbreak rate were observed in APS-supplemented groups after being infected by A. hydrophila. In conclusion, Furong crucian carp fed by APS-supplemented diets possesses elevated weight gain rate and specific growth rate, and improved meat quality, immunity and disease resistance.

Dual-color imaging of magnesium/calcium ion activities with two-photon fluorescent probes.

We report two-photon probes (FMg1 and FMg2) that can selectively detect intracellular free Mg(2+) ([Mg(2+)](i)) in live cells and tissues by two-photon microscopy. Combined with BCaM, a two-photon probe for near-membrane Ca(2+) ([Ca(2+)](m)), FMg2 allows dual-color imaging of Mg(2+)/Ca(2+) activities in live cells and [Mg(2+)](i) /[Ca(2+)](m) distributions in live tissues at a depth of 100-200 µm.

Two-photon fluorescent probe for cadmium imaging in cells.

A novel two-photon excited fluorescent probe for cadmium (named as TPCd) was designed and synthesized utilizing a prodan (6-acetyl-2-methoxynaphthalene) derivative as the two-photon fluorophore and an o-phenylenediamine derivative as the Cd(2+) chelator, which possessed favorable photophysical properties and good water-solubility. The probe was designed with a photoinduced electron transfer (PET) mechanism and thus was weakly fluorescent itself. After binding with Cd(2+) which blocked the PET process, the fluorescence intensity of the probe was enhanced by up to 15-fold under one-photon excitation (OPE) and 27-fold under two-photon excitation (TPE), respectively. The two-photon action cross-section (Φδ) of the TPCd-Cd complex at 740 nm reached 109 GM compared to 3.6 GM for free TPCd, indicating the promising prospect of the probe in two-photon application. TPCd chelated Cd(2+) with 1 : 1 stoichiometry, and the apparent dissociation constant (K(d)) was 6.1 × 10(-5) M for the one-photon mode and 7.2 × 10(-5) M for the two-photon mode. The probe responded to Cd(2+) over a wide linear range from 0.1 to 30 µM with a detection limit of 0.04 µM. High selectivity of the probe towards Cd(2+) was acquired in Tris-HCl/sodium phosphate buffer. The probe was pH-independent in the biologically relevant pH range and non-toxic to living cells at reasonable concentration levels, warranting its in vivo applications. Through two-photon microscopy imaging, the probe was successfully applied to detect Cd(2+) uptake in living HepG2 cells.

Experimental Investigation on the Pore Structure Evolution of Coal in Underground Coal Gasification Process.

Underground coal gasification (UCG) has been shown to be a promising method for deep coal resources. A series of complicated chemical reactions can induce a considerable change in the pore structure of coal and thus promote the UCG process in turn. Currently, most studies on the effect of elevated temperature on the pore structure of coal were not involved in an air atmosphere, bringing a series of difficulties to understanding the pore structure evolution of gasified coal in the UCG process. The objective of this work was to investigate the pore structure evolution of coal heated in nitrogen and air atmospheres at elevated temperatures. Thermogravimetry tests were first conducted to gasify coal samples, and then, the method scanning electron microscopy was used to observe the microscopic morphology of the pore structure. Besides, the effect of final temperature, atmosphere, pressure, and residence time on the thermal dynamics of coal at elevated temperatures was comprehensively discussed. Results indicated that the temperature range of a heating process of coal can be classified into three stages, 25-320 °C, 320-750 °C, and 750-1000 °C. For the three temperature ranges, drying, primary pyrolysis, and secondary pyrolysis can dominate, respectively, under a nitrogen atmosphere, while the combustion and gasification process will prevail at a high temperature under an air atmosphere. Because of mass loss, the coal was becoming porous during the heating process. Compared with the intact structure of coal when the temperature is lower than 300 °C, the pore space can interconnect under moderate-temperature conditions (500 °C) like a honeycomb, and then, only an ash framework remained under a higher-temperature condition (700 °C) under an air atmosphere. In comparison, the coal heated in a nitrogen atmosphere can gradually turn into a porous char. This investigation can provide some new insights into the pore structure evolution of gasified coal and contribute to the mechanisms of a UCG process.

Two-photon excited fluorescent chemosensor for homogeneous determination of copper(II) in aqueous media and complicated biological matrix.

In the present work, a two-photon excited fluorescent chemosensor for Cu(2+) was prepared. The probe was constructed on the basis of internal charge transfer (ICT) principle with macrocyclic dioxotetraamine as the Cu(2+) receptor. The good water-solubility of the molecule enabled recognition and assay of Cu(2+) ions in biological media. The photophysical properties of the chemosensor were investigated in detail, exhibiting favorable fluorescence quantum yield and moderate two-photon absorption cross-section. The studies on binding thermodynamics demonstrated the formation of 1 : 1 complex between the chemosensor and Cu(2+) and an association constant of ca. 1.04 × 10(5) M(-1). Due to the rational design of the molecular structure, the sensor was highly specific to Cu(2+), which ensured high selectivity in Cu(2+) determination. Upon Cu(2+) binding, the intramolecular charge-transfer extent within the chromophore was weakened resulting in a remarkable quenching of fluorescence, based on which quantitative determination of Cu(2+) was performed. Good linearity was obtained between the fluorescence quenching value and Cu(2+) concentration ranging from 0.04 to 2.0 µM in aqueous solution. Benefiting from the merits of two-photon excitation, the chemosensor was free of interference from background luminescence in serum. A homogeneous quantitative determination of Cu(2+) was achieved in the serum medium with a linear range of 0.04 to 2.0 µM. Considering the structural flexibility of the sensor, this work also opens up the possibility to construct other two-photon excited chemosensors for direct homogeneous assay of various molecules/ions in complicated biological sample matrices.

Polymer Flooding in Heterogeneous Heavy Oil Reservoirs: Experimental and Simulation Studies.

Polymer flooding (PF) in heterogeneous heavy oil reservoirs is not only closely related to polymer degradation, but also to non-Newtonian flow. In this paper, both experimental and simulation methods are combined to investigate this type of flooding. Through experiments, the degradation of polymer, rheological properties of fluids, and flow of fluids in porous media were determined. Based on the experimental results, a novel mathematical model was established, and a new PF simulator was designed, validated, and further applied to study the effects of polymer degradation, polymer solution shear thinning, and non-Newtonian flow on PF in heterogeneous heavy oil reservoirs. These experimental results demonstrated that the polymer first-order static degradation rate constant was lower than the polymer first-order dynamic degradation rate constant; the polymer solution and heavy oil were non-Newtonian fluids, with shear thinning and Bingham fluid properties, respectively; and the heavy oil threshold pressure gradient (TPG) in low-permeability porous media was higher than that in high-permeability porous media. All comparison results showed that the designed simulator was highly accurate and reliable, and could well describe both polymer degradation and non-Newtonian flow, with special emphasis on the distinction between polymer static and dynamic degradation and heavy oil TPG. Furthermore, the simulation results verified that polymer degradation, polymer solution shear thinning, and heavy oil TPG all had negative effects on the efficiency of PF in heterogeneous heavy oil reservoirs.

Visual Filling Model Experiment Study on the Enhanced Oil Recovery Mechanism of Novel Polymer Viscosity Reducer Flooding in Heavy Oil Reservoirs.

Chemical flooding is an effective method to enhance heavy oil recovery, and the viscosity reducer is often injected into the formation as the main reagent of chemical flooding. In the paper, a novel polymer viscosity reducer (FMP) was used to inject into a visual filling model, which can simulate the reservoir. The mechanism of enhancing heavy oil recovery by FMP is studied by macroscopic and microscopic analysis methods. The model can obtain macroscopic images and production data, including pressure, water cut, and oil recovery. The model can observe some microscopic processes, which can analyze the mechanism of enhanced oil recovery. Five processes of emulsifying viscosity reduction are summarized by using microscopic images: membrane oil removal, gradual emulsification, flocculation into droplet groups, active dispersion, and agglomeration into droplets. The FMP molecules can affect the interfacial properties of oil, water, and rock to enhance the wishing oil efficiency. Moreover, the decrease in the stability of the oil-water interface leads to flocculation into droplet groups and agglomeration into droplets occurring at the throat of the strong seepage zone, which increases the sweep coefficient from 0.56 to 0.90. The oil recovery has increased from 18 to 34%, which indicates that the FMP flooding obviously enhances the effect of heavy oil reservoir development.

Homogeneous competitive hybridization assay based on two-photon excitation fluorescence resonance energy transfer.

Recently, we have successfully developed a two-photon excitation fluorescence resonance energy transfer (TPE-FRET)-based homogeneous immunoassay using two-photon excitable small organic molecule as the energy donor. In the present work, the newly emerging TPE-FRET technique was extended to the determination of oligonucleotide. A new TPE molecule with favorable two-photon action cross section was synthesized [2-(2,5-bis(4-(dimethylamino)styryl)-1H-pyrrol-1-yl)acetic acid, abbreviated as TP-COOH], with the tagged reactive carboxyl group allowing facile conjugation with streptavidin (SA). Employing the TP-COOH molecule as energy donor and black hole quencher 1 (BHQ-1) as acceptor, a TPE-FRET-based homogeneous competitive hybridization model was constructed via a biotin-streptavidin bridge. Through the hybridization between a biotinylated single-stranded DNA (ssDNA) and a BHQ-1-linked ssDNA, and the subsequent capture of the as-formed hybrid by TP-COOH labeled SA, the donor fluorescence was quenched due to the FRET between TP-COOH and BHQ-1. Upon the competition between a target ssDNA and the quencher-linked ssDNA toward the biotinylated oligonucleotide, the donor fluorescence was recovered in a target-dependent manner. Good linearity was obtained with the target oligonucleotide ranging from 0.08 to 1.52 microM. The method was applied to spiked serum and urine samples with satisfying recoveries obtained. The results of this work verified the applicability of TPE-FRET technique in hybridization assay and confirmed the advantages of TPE-FRET in complicated matrix.

Two-photon excited fluorescent probes for calcium based on internal charge transfer.

Two-photon excited (TPE) calcium fluorescent probes are designed and synthesized based on internal charge transfer (ICT) with high Ca(2+) affinity and large two-photon action cross section, which can be used in living cells and detected with two-photon microscopy (TPM).

Homogeneous immunoassay based on two-photon excitation fluorescence resonance energy transfer.

A two-photon excitable small organic molecule (abbreviated as TP-NH 2) with large two-photon absorption cross section and competitive fluorescence quantum yield was prepared, which emitted fluorescence in the visible region upon excitation at 800 nm. Using the TP-NH 2 molecule as an energy donor, a two-photon excitation fluorescence resonance energy-transfer (TPE-FRET) based homogeneous immunoassay method was proposed. The donor and the acceptor (DABS-Cl, a dark quencher) were labeled to bovine serum albumin (BSA) separately, and anti-BSA protein was determined by employing an antibody bridging assay scheme. Rabbit anti-BSA serum containing other biomolecules was intentionally used as the sample to introduce interference. A parallel assay was performed using the traditional one-photon excitation FRET model, which failed to carry out quantitative determination due to the serious background luminescence arising from those biomolecules in the sample. The TPE-FRET model showed its strong ability to overcome the problem of autofluorescence and provided satisfying analytical performance. Quite good sensitivity and wide linear range (0.05-2.5 nM) for anti-BSA protein was obtained. The results of this work suggest that TPE-FRET could be a promising technique for homogeneous assays excluding separation steps, especially in complicated biological sample matrixes.

Effect of Polymer Degradation on Polymer Flooding in Heterogeneous Reservoirs.

Polymer degradation is critical for polymer flooding because it can significantly influence the viscosity of a polymer solution, which is a dominant property for polymer enhanced oil recovery (EOR). In this work, physical experiments and numerical simulations were both used to study partially hydrolyzed polyacrylamide (HPAM) degradation and its effect on polymer flooding in heterogeneous reservoirs. First, physical experiments were conducted to determine basic physicochemical properties of the polymer, including viscosity and degradation. Notably, a novel polymer dynamic degradation experiment was recommended in the evaluation process. Then, a new mathematical model was proposed and an in-house three-dimensional (3D) two-phase polymer flooding simulator was designed to examine both polymer static and dynamic degradation. The designed simulator was validated by comparison with the simulation results obtained from commercial software and the results from the polymer flooding experiments. This simulator further investigated and validated polymer degradation and its effect. The results of the physical experiments showed that the viscosity of a polymer solution increases with an increase in polymer concentration, demonstrating their underlying power law relationship. Moreover, the viscosity of a polymer solution with the same polymer concentration decreases with an increase in the shear rate, demonstrating shear thinning. Furthermore, the viscosity of a polymer solution decreased with an increase in time due to polymer degradation, exhibiting an exponential relationship. The first-order dynamic degradation rate constant of 0.0022 day-1 was greater than the first-order static degradation rate constant of 0.0017 day-1. According to the simulation results for the designed simulator, a 7.7% decrease in oil recovery, after a cumulative injection volume of 1.67 pore volume (PV) was observed between the first-order dynamic degradation rate constants of 0 and 0.1 day-1, which indicates that polymer degradation has a detrimental effect on polymer flooding efficiency.

Effect of Non-Newtonian Flow on Polymer Flooding in Heavy Oil Reservoirs.

The flow of polymer solution and heavy oil in porous media is critical for polymer flooding in heavy oil reservoirs because it significantly determines the polymer enhanced oil recovery (EOR) and polymer flooding efficiency in heavy oil reservoirs. In this paper, physical experiments and numerical simulations were both applied to investigate the flow of partially hydrolyzed polyacrylamide (HPAM) solution and heavy oil, and their effects on polymer flooding in heavy oil reservoirs. First, physical experiments determined the rheology of the polymer solution and heavy oil and their flow in porous media. Then, a new mathematical model was proposed, and an in-house three-dimensional (3D) two-phase polymer flooding simulator was designed considering the non-Newtonian flow. The designed simulator was validated by comparing its results with those obtained from commercial software and typical polymer flooding experiments. The developed simulator was further applied to investigate the non-Newtonian flow in polymer flooding. The experimental results demonstrated that the flow behavior index of the polymer solution is 0.3655, showing a shear thinning; and heavy oil is a type of Bingham fluid that overcomes a threshold pressure gradient (TPG) to flow in porous media. Furthermore, the validation of the designed simulator was confirmed to possess high accuracy and reliability. According to its simulation results, the decreases of 1.66% and 2.49% in oil recovery are caused by the difference between 0.18 and 1 in the polymer solution flow behavior indexes of the pure polymer flooding (PPF) and typical polymer flooding (TPF), respectively. Moreover, for heavy oil, considering a TPG of 20 times greater than its original value, the oil recoveries of PPF and TPF are reduced by 0.01% and 5.77%, respectively. Furthermore, the combined effect of shear thinning and a threshold pressure gradient results in a greater decrease in oil recovery, with 1.74% and 8.35% for PPF and TPF, respectively. Thus, the non-Newtonian flow has a hugely adverse impact on the performance of polymer flooding in heavy oil reservoirs.

Methane storage in nanoporous material at supercritical temperature over a wide range of pressures.

The methane storage behavior in nanoporous material is significantly different from that of a bulk phase, and has a fundamental role in methane extraction from shale and its storage for vehicular applications. Here we show that the behavior and mechanisms of the methane storage are mainly dominated by the ratio of the interaction between methane molecules and nanopores walls to the methane intermolecular interaction, and a geometric constraint. By linking the macroscopic properties of the methane storage to the microscopic properties of a system of methane molecules-nanopores walls, we develop an equation of state for methane at supercritical temperature over a wide range of pressures. Molecular dynamic simulation data demonstrates that this equation is able to relate very well the methane storage behavior with each of the key physical parameters, including a pore size and shape and wall chemistry and roughness. Moreover, this equation only requires one fitted parameter, and is simple, reliable and powerful in application.