Penetration Barrier Research Articles

Sp-nitrogen and γ-ray modulating multiply γ-graphyne for anchoring Pt nanoparticles to boost oxygen reduction activity and stability

γ-Graphyne (GY) is a potential carbon support for anchoring platinum nanoparticles (Pt NPs) in oxygen reduction reaction (ORR). However, the high oxygen penetration barrier of primitive GY intercepts its application for ORR. Herein, based on the stronger negative charge density of sp-hybridized nitrogen (sp-N) atoms and the regulation of γ-ray irradiation on carbon nanostructure, a Pt/N50-GY catalyst with a multi-level pore structure, larger specific surface area (twice that of original GY) and more Pt NPs anchor sites was fabricated by sp-N doping and γ-ray irradiation, which reduced the oxygen penetration barrier of original GY, exposed more active sites, shortened ion migration path and accelerated mass transfer, thus improving the ORR performance. The ORR activity of Pt/N50-GY catalyst is superior to that of the commercial Pt/C and even more outstanding when compared with the mostly reported graphdiyne related and noble meal catalysts under lower catalyst loading. Additionally, the Pt/N50-GY catalyst showed superior stability to the commercial Pt/C. Our work breaks the bottleneck that GY can not be applied to ORR, and provides a breakthrough way for the application of GY in ORR.

Uncertainty-aware energy management strategies for PV-assisted refuelling stations with onsite hydrogen generation

One of the main barriers for the wide penetration of fuel cell electric vehicles is the lack of proper infrastructures for hydrogen transportation that hinders the implantation of refuelling stations. This barrier could be overcome by deploying onsite hydrogen generators based on mature electrolysis and hydrogen storage technologies. This way, the necessity of hydrogen transportation is avoided. In addition, electrolysers can be onsite supplied by means of renewable generators like photovoltaic panels, while the produced hydrogen can also be destined to generate electricity through fuel cells thus obtaining a monetary revenue. Thereby, the economy of the system may be improved in order to make viable this kind of infrastructures. However, the optimal coordination of the different assets is challenging and requires the use of energy management tools to pursue the optimal performance of the installation. In this kind of infrastructures, the energy management problem is performed under substantial uncertainties; moreover, these unknown parameters have a very different character. Thus, while energy pricing and renewable generation can be forecasted using conventional techniques, refuelling demand is highly unpredictable. To this end, this paper proposes a novel stochastic-interval model for the optimal scheduling of photovoltaic-assisted refuelling stations. The new proposal uses interval notation to model the inherent uncertainty of renewable generation and energy pricing, while the vehicle demand is modelled using a more suitable approach based on scenarios. In this regard, a comprehensive stochastic model for fuel cell electric vehicles is developed, which is based on reported driving behaviour and common characteristics of commercial vehicles. To solve the problem subjected to uncertainties, an iterative solution methodology is developed which allows adopting risk-seeker and risk-averse operational strategies. A case study is analysed to validate the new proposal and discussing the importance of the different economic activities that can be exploited in refuelling stations. Results reveal the importance of selling energy to the grid in order to complement the revenues obtained from refuelling; however, this process is highly impacted by uncertainties and the operational strategy, observing variations up to 50% in the total profit depending on the strategy adopted.

Finite element simulation of thermal stress in RF magnetron sputtered SiC coating as tritium penetration barrier

The magnitude of thermal stress in the tritium penetration barrier coating is crucial during RF (radio frequency) magnetron sputtering preparation. The thermal stress would cause the delamination or crack on the coating, which seriously affects the structural stability of the coating. In this work, a finite element model represented the SiC tritium penetration barrier coating system was established. The relevant parameters which affected the magnitude of thermal stress of the system were discussed in detail. The shear and radial stresses in the system were also evaluated in order to identify the locations where the materials were prone to failure. Then, the propagation of multiple surface cracks in the system was investigated. Finally, the thermal stress was optimized by an Al2O3 interlayer. The outcomes indicated that the addition of the Al2O3 interlayer alleviated the stress at the interface and enhanced the mechanical stability and adhesive strength of the coating.

Mechanical signatures of human colon cancers

Besides the standard parameters used for colorectal cancer (CRC) management, new features are needed in clinical practice to improve progression-free and overall survival. In some cancers, the microenvironment mechanical properties can contribute to cancer progression and metastasis formation, or constitute a physical barrier for drug penetration or immune cell infiltration. These mechanical properties remain poorly known for colon tissues. Using a multidisciplinary approach including clinical data, physics and geostatistics, we characterized the stiffness of healthy and malignant colon specimens. For this purpose, we analyzed a prospective cohort of 18 patients with untreated colon adenocarcinoma using atomic force microscopy to generate micrometer-scale mechanical maps. We characterized the stiffness of normal epithelium samples taken far away or close to the tumor area and selected tumor tissue areas. These data showed that normal epithelium was softer than tumors. In tumors, stroma areas were stiffer than malignant epithelial cell areas. Among the clinical parameters, tumor left location, higher stage, and RAS mutations were associated with increased tissue stiffness. Thus, in patients with CRC, measuring tumor tissue rigidity may have a translational value and an impact on patient care.

Renewable Energy Acceptance by Households: Evidence from Lithuania

Although renewable energy adoption in the residential sector has increased significantly in the EU due to the governmental policies, aiming to reduce the barriers of renewable energy penetration, the full potential of renewable energy deployment in households is still not realized due to the behavioral and other barriers. One of the most important factors in the adoption of renewable energy technologies in households is the decision-making to implement renewables; therefore, the behavioral economics insights should be taken into account during the analysis of renewable energy acceptance by households. The paper provides a systematic literature review on renewable energy use in households by analyzing policies and measures, which could increase the use of renewable energy in households by overcoming the major barriers. The dynamics of renewable energy consumption in EU households was performed by applying Eurostat data, and the empirical case study was conducted in Lithuania to understand the main reasons of renewable energy acceptance by the household. Even though the use of renewable energy sources has increased significantly in the EU member states during the recent years, the study has found the following most common barriers that the traditional policies are unable to overcome: (1) high upfront cost and long pay-back period, (2) a lack of information and knowledge, (3) low priority of environmental concern, (4) resistance to change; human habits. The case study shows that the majority of Lithuanian households would like to use renewable energy technologies in their homes, but they encounter financial difficulties and lack of infrastructure. The policy recommendations were developed based on the results of the conducted study.

Density functional theory study of rare earth Y, Ce and La-catalyzed oxidation mechanism of Ta(1 0 0) and Ta(1 1 0) surfaces

The density functional theory (DFT) calculations were conducted to study the adsorption and diffusion of oxygen on Ta(100) and Ta(110) with and without the substitution of rare earth (RE, RE = Y, Ce and La) in the surface layer, which aims to reveal the possible RE-catalyzed oxidation mechanism of those two surfaces. The calculated results show that the oxygen atoms are preferentially adsorbed on the hollow site of clean Ta(100) and Ta(110). The RE doping in the subsurface layer weakens the adsorption strength of oxygen on Ta(110), while it has a negligible influence on that on Ta(100). In contrast, the substitution of RE in the surface layer can enhance the adsorption ability of oxygen atom on the two surfaces, which is also proved by the analysis of Bader charge and electron localization function. Additionally, the oxygen atoms are predicted to preferentially occupy the octahedral site in the subsurface of Ta slabs with and without RE doping. The investigations of oxygen diffusion behaviors indicate that the RE, especially for La, doping in the surface layer decrease the energy barrier of oxygen penetration into Ta surface, and thus catalyze the oxidation process of Ta slabs. Those results could help to provide a fundamental basis for comprehending the oxidation mechanism of Ta surface with RE doping.

Abstract 385: iRGD mediated delivery of neoantigens to enable immunotherapy in integrin b5-rich tumors

Abstract Pancreatic duct adenocarcinomas are known for their abundant desmoplastic stroma that acts as a barrier for drug penetration and reduces treatment efficacy. iRGD is a tumor-penetrating peptide that initially targets αv integrins expressed on tumor vasculature with its RGD motif and then is proteolytically processed to expose a CendR motif (R/KXXR/K) that interacts with neuropilin-1 (NRP-1), leading to extravasation. We investigated the mechanism of iRGD tissue penetration and found that iRGD initially targets Carcinoma Associated Fibroblasts (CAFs) and then spreads to the tumor cells in a time dependent manner. CAF targeting was dependent on integrin β5 expression and CAFs induced upregulation of integrin β5 in the adjacent tumor cells in a TGF- β dependent manner. Drugs conjugated or co-administered with iRGD can penetrate deep into tumor tissue, significantly increasing the efficacy of chemotherapeutic agents in a variety of solid tumors. Our recent data shows that KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre (KPC) mice treated with iRGD co-administered with Gemcitabine increased survival compared to drug alone. In addition, we are using iRGD to deliver neoantigens to breast and pancreatic cancers to enable immunotherapy. These tumors have a low mutational burden and a very immunosuppressive microenvironment, rendering them resistant to such therapies. We have used iRGD, to deliver the ovalbumin 257-264 (OVAI) peptide to triple negative breast tumors, followed by adoptive T cell transfer of OT1 CD8 T cells, in order to elicit an antitumor immune response. Our preliminary data showed tumor regression in 70%, and complete response in 42% of the mice treated with iRGD plus OVA1. We are now working on adapting this strategy to pancreatic cancer. Citation Format: Tatiana Hurtado de Mendoza, Evangeline S. Mose, Gregory P. Botta, Gary B. Braun, Venkata R. Kotamraju, Randall P. French, Kodai Suzuki, Norio Miyamura, Siming Sun, Jay Patel, Tambet Teesalu, Erkki Ruoslahti, Kazuki N. Sugahara, Andrew M. Lowy. iRGD mediated delivery of neoantigens to enable immunotherapy in integrin b5-rich tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 385.

Vortex nucleation barriers and stable fractional vortices near boundaries in multicomponent superconductors

The magnetization process of a superconductor is determined by the potential barrier for vortex nucleation and escape. In multicomponent superconductors, fractional vortices with a winding in the phase of only one of the components can be stable topological solitons that carry a fraction of the flux quantum. While the formation of such objects in the bulk costs logarithmically or linearly divergent energy, these objects were shown to be stable near the samples' boundaries in the two-component London model. Therefore the conventional Bean-Livingston picture of magnetic flux entry does not apply to these superconductors, since the entry process can involve fractionalization of a vortex. In this paper, we address the nonlinear problem of determining the potential barrier for fluxoid penetration in a multicomponent superconductor, including the effects of various intercomponent couplings, by using the recently developed gauged string method. The method allows numerically exact (i.e., convergent) calculation of a sphaleron configuration in a gauge theory and thus the height of the nucleation barrier. We show how the fractionalized nucleation processes result in multiple sphalerons and intermediate states due to the complex shape of the energy landscape of multicomponent superconductors.

Fluorescent Microscopy-Based Detection of Chitin in Intact Drosophila melanogaster.

Chitin is the major scaffolding component of the insect cuticle. Ultrastructural analyses revealed that chitin adopts a quasi-crystalline structure building sheets of parallel running microfibrils. These sheets called laminae are stacked either helicoidally or with a preferred orientation of the microfibrils. Precise control of chitin synthesis is mandatory to ensure the correct chitin assembly and in turn proper function of cuticular structures. Thus, evaluation of chitin-metabolism deficient phenotypes is a key to our understanding of the function of the proteins and enzymes involved in cuticle architecture and more generally in cuticle biology in insects. Usually, these phenotypes have been assessed using electron microscopy, which is time-consuming and labor intensive. This stresses the need for rapid and straightforward histological methods to visualize chitin at the whole tissue level. Here, we propose a simple method of chitin staining using the common polysaccharide marker Fluorescent brightener 28 (FB28) in whole-mount Drosophila melanogaster. To overcome the physical barrier of FB28 penetration into the cuticle, staining is performed at 65°C without affecting intactness. We quantify FB28 fluorescence in three functionally different cuticular structures namely wings, dorsal abdomens and forelegs by fluorescence microscopy. We find that, as expected, cuticle pigmentation may interfere with FB28 staining. Down-regulation of critical genes involved in chitin metabolism, including those coding for chitin synthase or chitinases, show that FB28 fluorescence reflects chitin content in these organs. We think that this simple method could be easily applied to a large variety of intact insects.

First principles study of hafnium intercalation between graphene and Ir(111) substrate

The intercalation of heteroatoms between graphene and metal substrates is a promising method for integrating epitaxial graphene with functional materials. Various elements and their oxides have been successfully intercalated into graphene/metal interfaces to form graphene-based heterostructures, showing potential applications in electronic devices. Here we theoretically investigate the hafnium intercalation between graphene and Ir(111). It is found that the penetration barrier of Hf atom is significantly large due to its large atomic radius, which suggests that hafnium intercalation should be carried out with low deposition doses of Hf atoms and high annealing temperatures. Our results show the different intercalation behaviors of a large-size atom and provide guidance for the integration of graphene and hafnium oxide in device applications.

Partial ligand shielding nanoparticles improve pancreatic ductal adenocarcinoma treatment via a multifunctional paradigm for tumor stroma reprogramming

The dense stroma that acts as a physical and biological barrier in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) leads to the failure of chemotherapeutic drug delivery. Cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) mainly constitute the refuge for cancer cells in PDAC. Herein, a CAF targeting drug delivery system (TDDS) based on RBC vesicles partial protection (RBC-Fn-NP) was established and investigated for reprogramming stroma, as well as enhancing tumor penetration and antitumor efficacy in PDAC. RBC vesicles were firstly used for partial protection of peptide from external influences. The exposed FnBPA5 peptide showed high affinity with both CAFs and the major components as collagen I and relaxed-fibronectin of ECM. Retinoic acid (RA) could disturb Golgi of CAFs, resulting in the reduction of protein secretion from the headstream. As expected, the strategy of RBC vesicles protected FnBPA5 targeting and RA-induced protein reduction was confirmed to reprogram the dense stroma and improve the penetration of Doxorubicin (Dox) in PDAC. RBC-Fn-NP inhibited tumor growth in both Pan02-orthotopic bearing model and Pan02-subcutaneous mice model. Hence, these partial ligand shielding nanoparticles offer a multifunctional and efficient approach to overcome penetration barriers and enhance the antitumor efficacy of chemotherapy in PDAC. Statement of significanceA partial ligand shielding nanoparticle platform (RBC-Fn-NP), which has the function of an RBC vesicle “shell” and thetargeting properties of a “core” to achieve superior therapeutic effects against PDAC, was established. The targeted ligand was modified on the surface of the nanoparticles instead of the RBC membranes. Three-dimensional PDAC stroma-rich spheroids were established to evaluate the penetration and tumor stroma remodeling. The targeting properties of FnBPA5 peptide, the effect of RA-induced Golgi disruption on the reduction of protein secretion, and the incomplete “camouflage” of the RBC vesicles were confirmed both in vitro and in vivo. As expected, our nanoplatform may provide a promising strategy for remolding dense stroma and enhancing the permeability in PDAC.

No interface energy barrier and increased surface pinning in low temperature baked niobium

Superconducting Radio-Frequency cavities are currently made out of niobium. Niobium cavities are limited by the magnetic field on the cavity walls due to the entry of vortices at the field of first vortex penetration, H_{vp}. Low temperature baking in vacuum or low pressure gas atmosphere removes the strong decrease of the quality factor with accelerating gradient (high field Q-slope). Some cavities reach surface magnetic field above the lower critical field H_{c1}. One hypothesis for this performance increase is that the outer layer affected by the treatments acts as a barrier for vortex penetration (effective bilayer). Using a vibrating sample magnetometer the field of first flux penetration (H_{vp}) was measured for Nb ellipsoids with various low temperature treatments. All H_{vp} values were found to be consistent with the lower critical field, H_{c1}, as predicted for clean niobium. This led to the conclusion that a metastable flux free state above H_{c1} cannot be observed in DC magnetometry for low temperature baked niobium unlike for bilayers consisting of two superconductors as previously published. The effect of flux pinning differed significantly between treatments, suggesting that the high field Q-slope mitigation might be related to vortex pinning in the surface of the cavities.

Fast proton-selective transport through covalent organic frameworks in aqueous phase

Covalent organic frameworks (COFs) are expected to be promising candidates as the building block for proton-exchange membranes (PEMs) due to their ordered well-defined nanopore structures with high density and tunable sizes. However, the mechanism of proton-selective transport through COF membranes is still unraveled. We herein investigate the proton-selective transport behaviors through four types of COFs in the aqueous phase. Proton can transport through COF membranes whose effective pore size >8 Å with low free energy barriers of <10 kJ mol−1. Furthermore, molecular analyses manifest that nucleophilic sites on the pore-wall can provide additional pathways for proton and promote the vehicular and Grotthuss transports via increasing the quantities and durability of in-pore hydrogen bonds. This dramatically reduces the energy barrier from ∼42 to ∼12 kJ mol−1 for proton transport especially under confinement (effective pore size <4 Å). Meanwhile, all COF membranes show relatively high methanol penetration barriers. Therefore, COFs with nucleophilic sites or relatively large pores can provide both high proton conductivity (16–60 S m−1) and selectivity (>1 × 104). The revealed mechanisms in this work are expected to not only increase our understandings of proton transport, but also help to design next-generation PEMs with exceptional permselectivity.

Carbon ene-yne working in oxygenator: A theoretical study

Traditional hollow-fiber membranes (HFM) in the oxygenator are in short supply due to their complicated manufacturing process, high price, and tight production capacity. To address these challenges, herein we designed a simplified molecular dynamics (MD) model that mimics the working procedure of HFM to explore whether carbon ene-yne (CEY) and other two carbon-based 2-dimensional (2D) materials: γ-graphyne and graphdiyne (GDY) could be used in an oxygenator. With the aid of the Density Functional based Tight Binding (DFTB) method, Density Functional Theory (DFT), Adaptive Steered Molecular Dynamics (ASMD), and NVT molecular dynamics (MD) simulations, the penetration barriers of the O2, CO2, and H2O molecules through these three 2D membranes are estimated. Furthermore, their permeance under various differential pressures are also discussed. According to our simulations, the CEY membrane can provide a much better performance for O2 and CO2 exchange than the most commonly used HFM material. CEY should be a promising candidate as O2 and CO2 exchange membrane working in the oxygenator.

The powerful synergistic effect of spiramycin/propolis loaded chitosan/alginate nanoparticles on acute murine toxoplasmosis.

The novel formula of spiramycin/propolis loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) was assessed for Toxoplasma gondii (T. gondii) treatment in comparison with the commercially available spiramycin regarding tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally by 2500 tachyzoites of the virulent T. gondii RH strain. The experimental groups were treated with oral spiramycin, propolis, CS/Alg NPs, spiramycin loaded CS/Alg NPs, propolis loaded CS/Alg NPs, and spiramycin/propolis loaded CS/Alg NPs. The results demonstrated that spiramycin/propolis loaded CS/Alg NPs exerted the longest survival time with no mortality on the sacrifice day (8th) in addition to representing the highest significant parasite percent reduction of (≥96% reduction) in liver, spleen and brain designating successful tissue penetration and BBB passage. Tachyzoites treated with spiramycin/propolis loaded CS/Alg NPs demonstrated the most disfigured rapturing organism via scanning electron microscope examination along with representing an overall remarkable improvement of the histopathological pictures of liver, spleen and brain. In conclusion, spiramycin/propolis loaded CS/Alg NPs showed the uppermost efficacy in the treatment of acute murine toxoplasmosis. The safe nature and the anti-parasitic effect of each of CS, Alg, spiramycin and propolis encourage the synergistic use of spiramycin/propolis loaded CS/Alg NPs as a potent treatment for human toxoplasmosis.

Elucidating of new hydrazide-based complexes derived from Pd(II), Cu(II) and Cd(II) ions: studies concerning spectral, DFT, Hirshfeld-crystal, biological screening beside Swiss-ADME verification

A new hydrazide ligand (HL) was characterized to be used for synthesis of some bivalent complexes via a green approach that free from hazard solvents. All synthesizes were analytically, spectrally and computationally characterized by using all available techniques. A bis-ligands were coordinated with Pd(II) and Cd(II) ions through neutral bidentate mode of C=O and C=N groups. While, a mono-ligand was coordinated with Cu(II) ion through a mono-negative tridentate mode. Such mode of bonding was suggested based on IR and NMR analysis and then confirmed computationally. The charges on N(10), O(12) and N(13) atoms in the ligand indicate their high nucleophilicity. The complexes were suggested in octahedral or square-planer geometry according to UV-Vis spectra and ESR spectrum of Cu(II) complex. The g-factors and anisotropic parameters supported the square planer geometry of [CuCl(L)] complex. The thermogravimetric (TGA) and kinetic analyses were studied for all complexes and supporting their freedom from water molecules and non-spontaneity of degradation stages. Some physical properties were estimated from modelling study and the superiority of most complexes over HL was noticed. Furthermore, all the compounds were tested in vitro against microbial strains and the Cu(II) complex showed high activity. Also, the antioxidant activity was tested by two methods as well as the cytotoxicity was tested against Ehrlich ascites cells and the Cu(II) or Pd(II) complex plays excellent. It is worthy to note that, the in-vitro results were supported by utilizing Swiss-ADME link. The pharmacokinetics of the small molecules (HL & [CuCl(L)]) were calculated to rank their bioavailability via such in-silico way that navigating at various Swiss Drug Design tools. The BOILED-Egg was also obtained to evaluate HIA and BBB as the indicators of passive gastrointestinal absorption and brain penetration barrier, respectively. The blue point appeared in Cu(II) complex egg indicates its effective effluxes by P-glycoprotein (P-gp), whereas the red point appeared in HL egg points to the non-substrate role of HL versus P-gp. Moreover, the ligand appeared oriented mainly towards MAP kinase and mixed lineage kinase 7 by 53.3%, while, the Cu(II) complex appeared oriented mainly towards GABA-A receptors as ligand-gated ion channel by 42.9%.

Finite Element Simulation of Thermal Stress in Sic Coating as Tritium Penetration Barrier

Finite Element Simulation of Thermal Stress in Sic Coating as Tritium Penetration Barrier

PH-Responsive size-shrinkable mesoporous silica-based nanocarriers for improving tumor penetration and therapeutic efficacy.

Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across the dense tumor matrix. Herein, we design a size-shrinkable nanocarrier that uses acid as a means of triggering a change in particle size for co-achievement of efficient tumor accumulation followed by deep tumor penetration and rapid clearance from the body. This nanocarrier is constructed from a pH-sensitive lipid layer shell and an ultrasmall amino-functionalized mesoporous silica nanoparticle core capable of loading drugs. After intravenous injection into mice bearing the 4T1 tumor, the nanocarrier with an initial hydrodynamic size of about 33 nm could effectively accumulate at the tumor site through the enhanced permeability and retention effect. Subsequently, in the acidic tumor microenvironment, the lipid layer comprising 9 alkyl-spiropyran (SP-C9) undergoes a volume shrinkage due to the conversion of hydrophobic SP-C9 to amphiphilic 9 alkyl-merocyanine (MC-C9), thus leading to a significant decrease in the entire particle size (hydrodynamic size ∼17 nm) for enhanced intratumoral penetration. Moreover, we find that this size-shrinkable nanocarrier could be rapidly excreted out of the body based on the ICP analysis, significantly reducing biosafety issues. Benefiting from the effective tumor accumulation and penetration of the nanocarrier, the released doxorubicin shows potent antitumor efficacy. This demonstrates the high potential of the designed nanocarrier in solid tumor treatment.

2D Co-UMOFNs filled PEBA composite membranes for pervaporation of phenol solution

Two-dimensional Co ultrathin metal–organic framework nanosheets (Co-UMOFNs) were synthesized and blended into poly (ether block amide) (PEBA) to prepare composite mixed matrix membranes on PVDF supports for the pervaporation of phenol aqueous solution. The membranes were characterized by XRD, ATR-IR, TGA, CA and SEM measurements. Effects of the Co-UMOFNs loading, feed temperature and feed concentration on phenol separation performance were investigated. The results showed that Co-UMOFNs have a two-dimensional layered morphology and have good compatibility with the PEBA. A “brick and mortar” architecture morphology was achieved after incorporating Co-UMOFNs into the PEBA membrane. The amorphous PE segments in the PEBA were turned into a crystalline structure, restricting the motion of PE segments. The filling of Co-UMOFNs slightly improved the thermal stability and hydrophobicity as well. With the increase of the Co-UMOFNs loading from 0% to 40%, the phenol separation factor increased from 27 to 45, and the total flux decreased from 1.2 kg m-2h-1 to 0.42 kg m-2h-1, when separation of 1000 ppm phenol solution at 70 °C. The interlayer galleries induced by the Co-UMOFNs stacking increased the tortuosity, and the crystalline structure of the Co-UMOFNs-PEBA improved the energy barriers of water penetration. Therefore the water flux was inhibited and the phenol separation factor increased. Depression of water permeation can be another protocol to prepare high-performance organophilic pervaporation membranes.

TIMP-1-expressing breast tumor spheroids for the evaluation of drug penetration and efficacy.

Abundance of stromal cells and extracellular matrix (ECM) is observed in breast cancer, acting as a barrier for drug penetration and presenting a key issue for developing efficient therapeutics. In this study, we aimed to develop a three‐dimensional (3D) multicellular tumor model comprising cancer and stromal cells that could effectively mimic the drug resistance properties of breast cancer. Three different types of spheroid models were designed by co‐culturing breast cancer cells (MDA‐MB‐231) with three different types of stromal cells: human adipose‐derived stromal cells (hASCs), human bone marrow stromal cells, or human dermal fibroblasts. Compared with other models, in the hASC co‐culture model, tissue inhibitor of metalloproteinases‐1 (TIMP‐1) was highly expressed and the activity of matrix metalloproteinases was decreased, resulting in a higher ECM deposition on the spheroid surfaces. This spheroid model showed less drug penetration and treatment efficacy than the other models. TIMP‐1 silencing in hASCs reduced ECM protein expression and increased drug penetration and vulnerability. A quantitative structure–activity relationship study using multiple linear regression drew linear relationships between the chemical properties of drugs and experimentally determined permeability values. Drugs that did not match the drug‐likeness rules exhibited lower permeability in the 3D tumor model. Taken together, our findings indicate that this 3D multicellular tumor model may be used as a reliable platform for efficiently screening therapeutics agents for solid tumors.