Penetration Of Molecules Research Articles

Controlling Anti-Penetration Performance by Post-Grafting of Fluorinated Alkyl Chains onto Polystyrene-block-poly(vinyl methyl siloxane).

Polydimethylsiloxane (PDMS) has been widely used as a surface coating material, which has been reported to possess dynamic omniphobicity to a wide range of both polar and nonpolar solvents due to its high segmental flexibility and mobility. However, such high flexibility and mobility also enable penetration of small molecules into PDMS coatings, which alter the chemical and physical properties of the coating layers. To improve the anti-penetration properties of PDMS, a series of fluorinated alkyl segments are grafted to a diblock copolymer of polystyrene-block-poly(vinyl methyl siloxane) (PS-b-PVMS) using thiol-ene click reactions. This article reports the chemical characterization of these model fluorosilicone block copolymers and uses fluorescence measurements to investigate the dye penetration characteristics of polymer thin films. The introduction of longer fluorinated alkyl chains can gradually increase the anti-penetration properties as the time to reach the maximum fluorescence intensity (tpeak) gradually increases from 11 s of PS-b-PVMS to more than 1000 s of PS-b-P(n-C6F13-VMS). The improvement of anti-penetration properties is attributed to stronger inter-/intrachain interactions, phase segregation of ordered fluorinated side chains, and enhanced hydrophobicity caused by the grafting of fluorinated alkyl chains.

A Study on the Effect and Suppression of Hydrogen Permeation Behavior on the Friction Characteristics of PEEK/PTFE Composites via Molecular Dynamics Simulation.

To research the effect of hydrogen permeation on the friction characteristics of the seal materials on the hydrogen equipment, the molecular models of 10% PEEK/PTFE composites and its frictional models were established, respectively, and molecular dynamics (MDs) and giant canonical Monte Carlo (GCMC) methods were used to simulate the diffusion coefficient, dissolution coefficient and permeability coefficient of the hydrogen in PEEK/PTFE composites. The effect of a different amount of hydrogen on the friction and wear of PEEK/PTFE composites was also studied. The results showed that few permeations of the hydrogen gas mainly demonstrated having a positive effect on the surface of the PEEK/PTFE composites, and the wear rate of the PEEK/PTFE composites showed a slight decreasing trend. The wear rate of the PEEK/PTFE composites gradually decreased when more hydrogen molecules penetrated the matrix. With the further penetration of the hydrogen molecules, the wear rate and friction coefficient of the PEEK/PTFE composites rapidly increased, showing a negative effect. With the further penetration of the hydrogen molecule, the friction coefficient of the composite displayed a small fluctuation and then a rapid decreasing trend. Meanwhile, effective improvement measures were proposed, and the introduction of the graphene was verified to be effective to reduce the negative effect of the hydrogen permeation, thereby improving the friction performance of the PEEK/PTFE composites.

Abstract 4774: Inhibition of pancreatic acinar ductal metaplasia by novel YAP/TAZ inhibitor, CV-4-26

Abstract Current challenges for pancreatic ductal adenocarcinoma (PDAC) treatment include overcoming the disease’s fibrous tumor microenvironment with limited cytotoxicity- in which tissue stiffening is believed to occur even pre-disease onset. Acinar to ductal metaplasia (ADM), the transdifferentiation of acinar cells into duct-like cells, is a predisposing event to PDAC development that is also linked to Hippo signaling, a major pathway involved in fibrosis and inflammation. Hippo activation is initiated by the yes-associated protein (YAP) in conjunction with the PDAZ binding motif (TAZ) and TEA domain (TEAD) transcription factor. Thus, the synthesis of the novel covalent TEAD autopalmitoylation inhibitor, CV-4-26, presented an opportunity to therapeutically target ADM. CV-4-26 binds to the TEAD lipid binding pocket, which, in turns, hinders TEAD palmitoylation, thereby leading to the inhibition of the Hippo pathway. Utilizing our 3D organoid p48Cre/+LSL-KRASG12D/+ (KC) mouse model, we demonstrated pronounced phenotypic and molecular inhibition of ADM by CV-4-26, resulting in a conserved acinar phenotype, as well as downregulation of downstream markers of the YAP/TAZ complex. The compound did not reverse ADM to the acinar state once ducts were visibly formed. Yet, CV-4-26 demonstrated a lack of cytotoxicity (up to 25 µM) as determined by Calcein AM staining. Biomechanical measurements of extracellular matrix stiffness acquired through calculations of fluorescent nanoparticle displacement further displayed decreased moduli as a response to inhibition treatment. Moreover, a 56-fold downregulation of collagen (COL1A1, COL1A2) mRNA, markers for PDAC development, was observed. However, less reduction in the collagens and extracellular matrix stiffness was observed in the ADM reversal treatments, corroborating our morphology and gene expression results. Our data suggest that combining CV-4-26 by ADM inhibition with standard of care therapies for PDAC may enhance the penetration of small molecules through the tumor’s extracellular matrix. Citation Format: Corey M. Perkins, Chen Zhou, Martha Campbell-Thompson, Yating Mao, Kalina R. Atanasova, Jinmai Jiang, Ranjala Ratnayake, Hendrik Luesch, Jamel Ali, Chenglong Li, Thomas D. Schmittgen. Inhibition of pancreatic acinar ductal metaplasia by novel YAP/TAZ inhibitor, CV-4-26 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4774.

Experimental and Computational Methods to Assess Central Nervous System Penetration of Small Molecules.

In CNS drug discovery, the estimation of brain exposure to lead compounds is critical for their optimization. Compounds need to cross the blood-brain barrier (BBB) to reach the pharmacological targets in the CNS. The BBB is a complex system involving passive and active mechanisms of transport and efflux transporters such as P-glycoproteins (P-gp) and breast cancer resistance protein (BCRP), which play an essential role in CNS penetration of small molecules. Several in vivo, in vitro, and in silico methods are available to estimate human brain penetration. Preclinical species are used as in vivo models to understand unbound brain exposure by deriving the Kp,uu parameter and the brain/plasma ratio of exposure corrected with the plasma and brain free fraction. The MDCK-mdr1 (Madin Darby canine kidney cells transfected with the MDR1 gene encoding for the human P-gp) assay is the commonly used in vitro assay to estimate compound permeability and human efflux. The in silico methods to predict brain exposure, such as CNS MPO, CNS BBB scores, and various machine learning models, help save costs and speed up compound discovery and optimization at all stages. These methods enable the screening of virtual compounds, building of a CNS penetrable compounds library, and optimization of lead molecules for CNS penetration. Therefore, it is crucial to understand the reliability and ability of these methods to predict CNS penetration. We review the in silico, in vitro, and in vivo data and their correlation with each other, as well as assess published experimental and computational approaches to predict the BBB penetrability of compounds.

First-principles study on the stability and degradation of the lead-free double perovskite materials Cs2B'BiCl6 (B' = Li, Na, K) under natural environment

The stability of perovskite solar cell materials in the natural environment is crucial to their commercial application. Understanding the detailed interaction mechanism between the air or water molecules (H2O) and the perovskite materials is a key way to explore their stabilities. In this study, we evaluate the geometric stabilities and thermodynamic stabilities of the lead-free Cs2B'BiCl6 (B' = Li, Na, K) double perovskite materials, and further explore the effect of air and H2O molecules on the stability and degradation of the Cs2B'BiCl6 double perovskite materials. The calculated results indicate that the pristine Cs2B'BiCl6 materials possess good geometric stabilities and thermodynamic stabilities. Under natural environment, the N2, O2, and CO2 gas molecules hardly penetrate into Cs2LiBiCl6 and Cs2NaBiCl6 because of positive absorption energies, while N2 and O2 can easily penetrate into Cs2KBiCl6 due to negative absorption energies. In contrast, the H2O molecules can easily penetrate into all Cs2B'BiCl6 double perovskite materials with negative absorption energies. Furthermore, the penetration of H2O molecules causes structural deformations of the double perovskites and the resultant rotation or rupture of some octahedra. Further simulations of H2O molecules adsorption on the surface of the double perovskites reveal that the adsorption energies of H2O molecules at all adsorption sites are negative, indicating that the Cs2B'BiCl6 double perovskite materials are prone to absorb H2O molecules in a humid environment. Therefore, the H2O molecules are the main factor affecting the stability and degradation of all Cs2B'BiCl6 double perovskite materials. Additionally, Cs2KBiCl6 shows much worse stability, which is responsible for the scarcely experimental reports on its synthesis and characterization.

Permeance of Condensable Gases in Rubbery Polymer Membranes at High Pressure.

The gas transport properties of thin film composite membranes (TFCMs) with selective layers of PolyActive™, polydimethylsiloxane (PDMS), and polyoctylmethylsiloxane (POMS) were investigated over a range of temperatures (10-34 °C; temperature increments of 2 °C) and pressures (1-65 bar abs; 38 pressure increments). The variation in the feed pressure of condensable gases CO2 and C2H6 enabled the observation of peaks of permeance in dependence on the feed pressure and temperature. For PDMS and POMS, the permeance peak was reproduced at the same feed gas activity as when the feed temperature was changed. PolyActive™ TFCM showed a more complex behaviour, most probably due to a higher CO2 affinity towards the poly(ethylene glycol) domains of this block copolymer. A significant decrease in the permeate temperature associated with the Joule-Thomson effect was observed for all TFCMs. The stepwise permeance drop was observed at a feed gas activity of p/po ≥ 1, clearly indicating that a penetrant transfer through the selective layer occurs only according to the conditions on the feed side of the membrane. The permeate side gas temperature has no influence on the state of the selective layer or penetrant diffusing through it. The most likely cause of the observed TFCM behaviour is capillary condensation of the penetrant in the swollen selective layer material, which can be provoked by the clustering of penetrant molecules.

Selective Uptake of Macromolecules to the Brain in Microfluidics and Animal Models Using the HAVN1 Peptide as a Blood-Brain Barrier Modulator.

Monoclonal antibodies (mAbs) possess favorable pharmacokinetic properties, high binding specificity and affinity, and minimal off-target effects, making them promising therapeutic agents for central nervous system (CNS) disorders. However, their development as effective therapeutic and diagnostic agents for brain disorders is hindered by their limited ability to efficiently penetrate the blood-brain barrier (BBB). Therefore, it is crucial to develop efficient delivery methods that enhance the penetration of antibodies into the brain. Previous studies have demonstrated the potential of cadherin-derived peptides (i.e., ADTC5, HAVN1 peptides) as BBB modulators (BBBMs) to increase paracellular porosities for penetration of molecules across the BBB. Here, we test the effectiveness of the leading BBBM peptide, HAVN1 (Cyclo(1,6)SHAVSS), in enhancing the permeation of various monoclonal antibodies through the BBB using both in vitro and in vivo systems. In vitro, HAVN1 has been shown to increase the permeability of fluorescently labeled macromolecules, such as a 70 kDa dextran, 50 kDa Fab1, and 150 kDa mAb1, by 4- to 9-fold in a three-dimensional blood-brain barrier (3D-BBB) microfluidics model using a human BBB endothelial cell line (i.e., hCMEC/D3). HAVN1 was selective in modulating the BBB endothelial cell, compared to the pulmonary vascular endothelial (PVE) cell barrier. Co-administration of HAVN1 significantly improved brain depositions of mAb1, mAb2, and Fab1 in C57BL/6 mice after 15 min in the systemic circulation. Furthermore, HAVN1 still significantly enhanced brain deposition of mAb2 when it was administered 24 h after the administration of the mAb. Lastly, we observed that multiple doses of HAVN1 may have a cumulative effect on the brain deposition of mAb2 within a 24-h period. These findings offer promising insights into optimizing HAVN1 and mAb dosing regimens to control or modulate mAb brain deposition for achieving desired mAb dose in the brain to provide its therapeutic effects.

The Signature of Fluctuations of the Hydrogen Bond Network Formed by Water Molecules in the Interfacial Layer of Anionic Lipids

As the water molecules found at the interface of lipid bilayers exhibit distinct structural and reorientation dynamics compared to water molecules found in bulk, the fluctuations in their hydrogen bond (HB) network are expected to be different from those generated by the bulk water molecules. The research presented here aims to gain an insight into temperature-dependent fluctuations of a HB network of water molecules found in an interfacial layer of multilamellar liposomes (MLVs) composed of anionic 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) lipids. Besides suspending DMPS lipids in phosphate buffer saline (PBS) of different pH values (6.0, 7.4, and 8.0), the changes in HB network fluctuations were altered by the incorporation of a non-polar flavonoid molecule myricetin (MCE) within the hydrocarbon chain region. By performing a multivariate analysis on the water combination band observed in temperature-dependent FTIR spectra, the results of which were further mathematically analyzed, the temperature-dependent fluctuations of interfacial water molecules were captured; the latter were the greatest for DMPS in PBS with a pH value of 7.4 and in general were greater for DMPS multibilayers in the absence of MCE. The presence of MCE made DMPS lipids more separated, allowing deeper penetration of water molecules towards the non-polar region and their restricted motion that resulted in decreased fluctuations. The experimentally observed results were supported by MD simulations of DMPS (+MCE) lipid bilayers.

Removal of ciprofloxacin-humic acid pollutant residue in wastewater through a hybrid treatment system consisting of pre-treatment with ozonation-AC/TiO2/CeO2 adsorption and degradation using PVDF/Ni-CeO2@SiO2 photocatalytic membrane

Photocatalytic membranes (PMs) provide an excellent removal efficiency for emerging pollutants (EPs) through simultaneous photocatalytic degradation and molecular separation. However, the fabrication of PMs from conventional photocatalytic nanoparticle suffers from low membrane performance, especially due to chemical incompatibility and maldistribution of the photocatalytic nanoparticles, and low photocatalytic caused by rapid recombination of e-/h+ pair. Prior to the preparation of PVDF/Ni-CeO2@SiO2 membrane (NCSM), nanocomposite photocatalyst of Ni-CeO2@SiO2 was firstly prepared according to the sol-gel method. The CeO2 photocatalyst was doped by Ni atom to improve its optical properties and followed by impregnation into SiO2 support to amplify the photocatalyst distribution. Then, the NCSM was further coated using polydopamine (PDA) to enhance permeate water flux. The NCSM exhibited significant structural porosity enhancement to ease water molecule penetration. The PDA coated NCSM demonstrated 1.2 times higher photocatalytic activity than the uncoated one. Indeed, the membrane has considerably high permeate flux up to ∼70.9 L.m−2.h−1 with ciprofloxacin and humic acid removal up to 99.9% and 98%, respectively. In addition, the NCSM also showed excellent antifouling properties that develop remarkable stability of 98% flux recovery after 3 cycles. Therefore, this study promotes a great potential of PMs for highly effective antibiotic eradication in wastewater.

Enhancing Gene Therapy through Ultradeformable Vesicles for Efficient siRNA Delivery.

Gene therapy is a revolutionary approach aimed at treating various diseases by manipulating the expression of specific genes. The composition and formulation of ultra-deformable vesicles play a crucial role in determining their properties and performance as siRNA delivery vectors. In the development of ultra-deformable vesicles for siRNA delivery, careful lipid selection and optimization are crucial for achieving desirable vesicle characteristics and efficient siRNA encapsulation and delivery. The stratum corneum acts as a protective barrier, limiting the penetration of molecules, including siRNA, into the deeper layers of the skin. Ultradeformable vesicles offer a promising solution to overcome this barrier and facilitate efficient siRNA delivery to target cells in the skin. The stratum corneum, the outermost layer of the skin, acts as a significant barrier to the penetration of siRNA.These engineering approaches enable the production of uniform and well-defined vesicles with enhanced deformability and improved siRNA encapsulation efficiency. Looking ahead, advancements in ultra-deformable vesicle design and optimization, along with continued exploration of combination strategies and regulatory frameworks, will further drive the field of ultra-deformable vesicle-based siRNA delivery.

Investigation of the shapes and sizes of soft molecular aggregates in solution via partial molar volume and dynamic light scattering measurements

Soft molecular aggregates are naturally dynamic and deformable nanoscale objects of various shapes and sizes. However, soft nanoparticle shape can be difficult to measure and often requires advanced instrumentation or methods. Yet, foreknowledge of soft aggregate overall shape is often critically important in many experiments that measure the aggregate’s internal structure and properties. Small-angle neutron and x-ray scattering are often used to measure soft nanoparticle shape. Molecular dynamics simulations can also give an indication of soft molecular shape but, like small-angle scattering methods, requires considerable expense and training. To complement these approaches a more straightforward experimental method of determining soft molecular aggregate shape using a combination of partial molar volume and dynamic light scattering measurements (PMV-DLS) is presented. PMV-DLS is inexpensive, requires modest instrumentation, and can be performed in any laboratory. In this article, the PMV-DLS technique is demonstrated on two separate soft molecular aggregates: AOT reverse micelles and Triton X-100 micelles. The shapes of these aggregates were investigated over a range of solution properties. In both cases, the penetration of continuous phase solvent molecules into the aggregate was found to play an important role in shape determination. AOT reverse micelles were observed to transition from ellipsoidal to spherical as the solution water content increased. Triton X-100 micelle shape was found to be critically dependent upon the amount of water that partitions into the surfactant polyethylene oxide head group region.

Recent Advances in Transdermal Drug Delivery System (TDDS): A Review

Abstract: The transdermal route of administration has many advantages over more traditional routes of drug administration. They contain high bioavailability, lack of first-pass hepatic metabolism, stable plasma drug concns., and fact that the treatment is non-invasive. The biggest barrier to the penetration of medicinal molecules is the outer layer of the skin, stratum corneum. Thus, research to improve transdermal drug delivery (TDD) is worthwhile this layer is the area of interest. This review article is written to provide coverage commentary recent advances in TDD improvement techniques. Techniques that improve the permeability of the skin have been used developed to improve bioavailability and increase the choice of topical and transdermal drugs is a viable option. This review describes enhancement techniques based on drug/vehicle optimization, e.g selection of drugs, prodrugs and ion pairs, supersaturated drug solutions, eutectic systems, complexes, liposomes, vesicles and particles. Strengthening by changing the shell with moisturizing chemical enhancers partitioning and solubility effects affecting crustal lipid and keratin structure discussed Mechanism of action of penetration enhancers and retarders and their potential for clinical use application is described.

STRUCTURE FORMATION OF IRON-CONTAINING DISPERSIONS OF ORGANOMONTMORYLONITE

The aim of the work is to study the processes of structure formation of organomontmorillonite in iron-containing dispersions by studying the rheological and colloid-chemical properties of such systems. To modify the surface of montmorillonite, a cationic surface-active substance, a quaternary ammonium salt, hexadecyltriammonium bromide, was used. With the help of X-ray diffraction analysis, we confirmed the penetration of molecules of surface-active substances into the interlayer space of the mineral and its increase to 1.86 nm during the modification mineral surfactant/ cation exchange capacity (S/CEC)=1. The analysis of the results of rheological studies showed that the changes in the characteristics of montmorillonite dispersions depending on the concentration of surfactants are extreme and reach a maximum (6.7 Pa) at the degree of modification of the mineral S/CEC=0.3. The high values of ultimate shear stress confirm the formation of a continuous network between the mineral particles with an "edge–face" orientation. When the surfactant content in the system increases, the ultimate shear stress of the suspension gradually decreases and reaches practically zero values. These results lay the foundation for determining the optimal parameters for the synthesis of iron-containing dispersions based on organomontmorillonite. nZVI was obtained by its reduction on the solid surface of organomodified montmorillonite from a solution of iron(II) sulfate salt. X-ray diffraction data confirmed the fixation of nZVI on the surface of organophilized montmorillonite. Analysis of the results of rheological studies showed that changes in the characteristics of dispersions of iron-containing material based on organomontmorillonite depending on the content of nZVI are extreme and reach a maximum at (6.8 Pa) when the iron content in the sorbent is 0.01 mass fraction in the solid phase of the sorbent. When the content of nZVI is increased to 0.05 mass fraction of the solid phase of the sorbent, it is possible to obtain dispersions with high values of ultimate shear stress (3.3 Pa) and clearly expressed hysteresis loops, which indicates the formation of thixotropic structures and confirms the possibility of its use in permeable reaction barriers. Experimental data confirm that with an increase in the content of nZVI above 0.1 mass fraction in the samples, the ultimate stress and plastic viscosity decrease, which leads to the failure of the suspensions. These results lay foundation for determining the optimal parameters of sorbents synthesis and regulation of their properties by changing the hydrophilic-hydrophobic balance of source systems.

Membraneless Ionic Liquid Droplet Nanoprobe for Vapor Sensing and Gas Phase Scanning Electrochemical Microscopy

Gas phase sensing of volatile chemicals is a critical area of research relevant to biomedical diagnosis and environmental hazard assessment. Among various types of sensors, electrochemical sensors garnered attention as cost-effective and portable methods. Most electrochemical sensors needed the membrane to prevent solvent evaporation for detecting the gaseous species. However, the presence of the membrane induced slow response time due to the penetration of gas molecules through the membrane. To improve the systems, a membraneless ionic liquid droplet nanoprobe was developed. Gaseous species can permeate the thin ionic liquid layer, which was also used as the electrolytes, and react on the electrode in extremely fast response. Furthermore, nano-sized electrode makes available to detect sensitively with low charging capacitance. Using the probe type form factor, application to gas phase scanning electrochemical microscopy (SECM) was attempted with high spatial resolution. Oxygen detection, the most commonly studied, was implemented for the first application of the ionic liquid nanoprobe. The limit of detection of this probe was 13 ppm, which is extremely good for electrochemical oxygen sensors. Also, the fast response (< 0.1 s) made the mapping of oxygen concentration using SECM. The nanoprobe showed more than a hundred times better spatial resolution (several micrometer scale) than the previous gas phase SECM study mapping the oxygen. As the application of this oxygen probe, Li-air battery analysis can be conducted. Oxygen was used in the reaction at the cathode of the Li-air battery. As mapping the oxygen concentration above the cathode, It is expected that structural causes for the irreversibility at the cathode can also be found. As oxygen sensing, other electrochemical active gaseous species can be detected with the electrochemical sensor. Trinitrotoluene is a well-known explosive compound, and it can be detected in electrochemistry. Due to its low vapor pressure, di-nitroaromatic compounds, like dinitrotoluene (DNT), dinitrobenzene (DNB), and dinitrophenol (DNP), were used as explosive footprints, which have higher vapor pressure and have often been identified as marker molecules. Using our ionic liquid nanoprobe, we developed the nitroaromatic compounds (NACs) sensor for real-time detection of trace vapors, without any sample pre-treatment and at room temperature. Furthermore, in a simulated airport carousel, real-time and preemptive NACs detection was demonstrated with fast response time. As oxygen detection, gas phase SECM was conducted and 3D mapping capability of the differential vapor pressure was demonstrated, exercising the potential of the NACs nanoprobe in locating the source of an explosive risk. With the sensitive sensing performance of nanoprobe, it can be used as breath analysis. There are several biomarkers to indicate certain diseases. For example, acetone is a representative biomarker of diabetes. Using this sensing platform, acetone sensing was implemented, and it may be used for the initial detection of diabetes.

Utilizing a Dual Human Transporter MDCKII-MDR1-BCRP Cell Line to Assess Efflux at the Blood Brain Barrier.

To facilitate the design of drugs readily able to cross the blood brain barrier (BBB), a Madin-Darby canine kidney (MDCK) cell line was established that over expresses both P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP), the main human efflux transporters of the BBB. Proteomics analyses indicate BCRP is expressed at a higher level than Pgp in this cell line. This cell line shows good activity for both transporters [BCRP substrate dantrolene efflux ratio (ER) 16.3 ± 0.9, Pgp substrate quinidine ER 27.5 ± 1.2], and use of selective transporter inhibitors enables an assessment of the relative contributions to overall ERs. The MDCKII-MDR1-BCRP ER negatively correlates with rat unbound brain/unbound plasma ratio, Kpuu Highly brain penetrant compounds with rat Kpuu ≥ 0.3 show ERs ≤ 2 in the MDCKII-MDR1-BCRP assay while compounds predominantly excluded from the brain, Kpuu ≤ 0.05, demonstrate ERs ≥ 20. A subset of compounds with MDCKII-MDR1-BCRP ER < 2 and rat Kpuu < 0.3 were shown to be substrates of rat Pgp using a rat transfected cell line, MDCKII-rMdr1a. These compounds also showed ERs > 2 in the human National Institutes of Health (NIH) MDCKI-MDR1 (high Pgp expression) cell line, which suggests that they are weak human Pgp substrates. Characterization of 37 drugs targeting the central nervous system in the MDCKII-MDR1-BCRP efflux assay show 36 have ERs < 2. In drug discovery, use of the MDCKII-MDR1-BCRP in parallel with the NIH MDCKI-MDR1 cell line is useful for identification of compounds with high brain penetration. SIGNIFICANCE STATEMENT: A single cell line that includes both the major human efflux transporters of the blood brain barrier (MDCKII-MDR1-BCRP) has been established facilitating the rapid identification of efflux substrates and enabling the design of brain penetrant molecules. Efflux ratios using this cell line demonstrate a clear relationship with brain penetration as defined by rat brain Kpuu.

Experimental and simulation investigation on hydrophobicity and corrosion resistance of graphene oxide reinforced composite coating

The graphene oxide (GO) was introduced to epoxy resin (EP) to prepare the GO/PVB/EP composite coating. The hydrophobicity and anti-corrosion performance of the composite coating were investigated experimentally through contact angle and electrochemical experiments. The experimental data showed that the contact angle was 60.43°, and the corrosion resistance rate of the PVB/EP coating reached 84.03%. After adding 0.89 wt% GO, the corrosion resistance rate of the composite coating reached 92.57%, which was 8.54% higher than that of the PVB/EP coating, and the contact angle reached 114.66°. Furthermore, the constructed GO/PVB/EP coating molecular dynamics model was proposed, and the performance of the GO for water drainage and antiseptic were analyzed. Due to the blockage of the GO monolayer, the effective water molecule penetration surface area in the GO/PVB/EP layer is smaller than that in the PVB/EP layer. As the contact angle of the GO/PVB-EP layer meets the small contact angle of the PVB/EP coating, the GO/PLB/EP coating has high corrosion resistance due to the PVB/EP coating.

Engineering a separation membrane containing a gel layer with backbone support effect and bionic-inspired capillary effect for the efficient separation of dyes/salts

Accurate separation of dyes/salts is a crucial step in the treatment of dye-containing wastewater. Therefore, separation membranes with high permeability and high dye/salt selectivity are urgently required. In this study, an ultrathin gel layer of carboxymethyl cellulose was constructed on a poly(vinylidene fluoride) membrane surface. This gel layer contains a backbone support structure and provides the bionic-inspired capillary effect, which endows the membrane with the capability to realize the efficient separation of dyes and salts. The introduction of silver nanoparticles (Ag NPs) into the gel layer provides a skeleton support structure, which prevents the collapse of the gel layer, reduces the actual separation layer thickness, and decreases the mass transfer resistance. Moreover, the formation of capillaries between the numerous Ag NPs facilitates the rapid penetration of water molecules. Interestingly, this membrane exhibited excellent selectivity for dye/salt separation (dye removal >99.5 %, salt removal <10 %) while maintaining an exceptionally high water permeate flux (244.5 L/m2h). Moreover, the membrane exhibited excellent stability. This study demonstrates that the construction of organic/inorganic three-dimensional structures with capillary and skeletal support effects show promise potential for modification of dye/salt separation membranes.

Molecular dynamics models to investigate the diffusion behavior of emulsified asphalt

The utilization of emulsified asphalt is widespread in the recycling of asphalt pavement due to its eco-friendliness and energy efficiency. While numerous research studies have been conducted on the mixture design and strength assessment of emulsified asphalt, the mechanism by which it diffuses and adheres to the aggregate surface remains inadequately comprehended. This study developed molecular dynamics models to investigate the diffusion behavior of emulsified asphalt on the aggregate surface to clarify the role of emulsifier, water, and asphalt in the adsorption process from a molecular perspective. Interface models are established according to the diffusion state for interfacial adhesion evaluation. The results show that the movement of water molecules is the driving force for the entire emulsified asphalt to adsorb to the aggregate surface, whether the aggregate is silica or reclaimed asphalt pavement (RAP). Compared with anionic surfactant Sodium Dodecylbenzene Sulfonate (SDBS), cationic emulsifier Cetyltrimethylammonium Chloride (CTAC) has a better affinity, stronger adsorption, and higher interfacial adhesion energy with silica. Compared with RAP, emulsified asphalt is more readily adsorbed to the surface of silica. It is concluded that emulsifiers have two distribution conformations during the adsorption process, delamination, and aggregation, with delamination exhibiting stronger interface strength with silica than aggregation. When the emulsified asphalt spreads on the RAP surface, the penetration of water molecules into the aged asphalt layer in the RAP structure reduces the structure's water resistance. These results can provide a molecular perspective for understanding the internal structure of emulsified cold recycle mixture (ECRM) and link the adsorption behavior of emulsified asphalt on aggregate surfaces with the internal interface strength of ECRM.

Surface tension and evaporation behavior of liquid fuel droplets at transcritical conditions: Towards bridging the gap between molecular dynamics and continuum simulations

The phase transition from subcritical to supercritical conditions, referred to as transcritical behavior, significantly impacts the evaporation and fuel–air mixing in high-pressure liquid-fuel propulsion systems. Transcritical behavior is characterized as a transition from classical two-phase evaporation to a single-phase gas-like diffusion regime as surface tension and latent heat of vaporization reduce. However, the interfacial behavior represented by the surface tension coefficient and evaporation rate during this transition which are crucial inputs for Computational Fluid Dynamics (CFD) simulations of practical transcritical fuel spray is still missing. This study aims at developing new evaporation rate and surface tension models for transcritical n-dodecane droplets using molecular dynamics (MD) simulations irrespective of the droplet size. As MD simulations are primarily limited to the nanoscale, the new models can bridge the gap between MD and continuum simulations and enable the direct application of these findings to microscopic droplets. A new characteristic timescale, i.e., “undroplet time,” is defined which marks the transition from classical two-phase evaporation to single-phase gas-like diffusion behavior. The undroplet time indicates the onset of droplet core disintegration and penetration of nitrogen molecules into the droplet, which occurs after the vanishment of the surface tension. By normalizing the time with respect to the undroplet time, the rate of surface tension decay, evaporation rate, and the rate of droplet mass depletion become independent of the droplet size. Calculation of pairwise correlation coefficients for the entire MD results shows that both surface tension coefficient and evaporation rate are strongly correlated with the background temperature, while pressure and droplet size play a less significant role past the critical point. Therefore, new models for surface tension coefficient and evaporation rate spanning from sub- to supercritical conditions are developed as a function of background pressure and temperature, which can be used in continuum simulations. The identified phase change behavior based on the undroplet time shows a good agreement with the phase change regime maps obtained using microscale experiments and nanoscale MD predictions.

Enhanced porous membrane fabrication using cellulose acetate and citric acid: Improved structural integrity, thermal stability, and gas permeability

In this study, our primary objective was to enhance the properties of porous membranes by addressing the limitations associated with phase separation. We employed a non-solvent induced phase separation (NIPS) method, utilizing cellulose acetate (CA) in conjunction with citric acid to fabricate these membranes. Citric acid played a dual role: ensuring a uniform pore structure and cross-linking the CA polymer, thereby enhancing its mechanical strength. This approach resulted in the development of a more robust membrane with superior structural integrity. Thermogravimetric analysis (TGA) confirmed enhanced thermal stability, particularly up to 150 °C, as a result of citric acid's cross-linking effect. Beyond 150 °C, the decomposition temperatures of the CA/citric acid membrane were found to be comparable to those of pure CA. Remarkably, a CA/citric acid ratio of 1:0.05 exhibited the slowest decomposition rate as the temperature increased. Scanning electron microscopy (SEM) examination unveiled a sponge-like membrane structure with numerous evenly distributed fine pores. Through the use of citric acid as a plasticizer, we were able to effectively control the penetration of water molecules, preventing the formation of macrovoids and promoting the creation of fine pores. This resulted in the fabrication of a high-porosity membrane, boasting an impressive porosity measurement of 84.9 %. Furthermore, measurements of the Gurley value confirmed efficient gas permeation, a critical characteristic for applications requiring effective gas transport. Fourier transform infrared (FT-IR) spectroscopy attested to the presence of citric acid in the membrane post-phase separation, indicating its successful integration. Our work presents a novel approach to enhance porous membranes, providing improvements in mechanical strength, thermal stability, and gas permeability. These findings offer valuable insights for the development of advanced materials with diverse applications in various fields.