Measuring Mass Transfer of n-Hexane and 2-Chloroethyl Ethyl Sulfide in Sorbent/Polymer Fiber Composites Using a Volumetric Adsorption Apparatus.

The integration of metal-organic frameworks (MOFs) into composite systems serves as an effective strategy to increase the processability of these materials. Notably, MOF/fiber composites have shown much promise as protective equipment for the capture and remediation of chemical warfare agents. However, the practical application of these composites requires an understanding of their mass transport properties, as both mass transfer resistance at the surface and diffusion within the materials can impact the efficacy of these materials. In this work, we synthesized composite fibers of MOF-808 and amidoxime-functionalized polymers of intrinsic microporosity (PIM-1-AX) and measured the adsorption and mass transport behavior of n-hexane and 2-chloroethyl ethyl sulfide (CEES), a sulfur mustard simulant. We developed a new Fickian diffusion model for cylindrical shapes to fit the dynamic adsorption data obtained from a commercial volumetric adsorption apparatus and found that mass transport behavior in composite fibers closely resembled that in the pure PIM fibers, regardless of MOF loading. Moreover, we found that n-hexane adsorption mirrors that of CEES, indicating that it could be used as a structural mimic for future adsorption studies of the sulfur mustard simulant. These preliminary insights and the new model introduced in this work lay the groundwork for the design of next-generation composite materials for practical applications.

KRT80 expression works as a biomarker and a target for differentiation in gastric cancer.

Keratin 80 (KRT80) is a filament protein that participates in cell differentiation and the integrity of the epithelial barrier. Here, KRT80 expression was higher in gastric cancer compared with normal mucosa at both mRNA and protein levels by bioinformatic analysis, qRT-PCR and Western blot (p<0.05), however, the methylation of KRT80 was lower than in normal mucosa (p<0.05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in gastric cancer (p<0.05). KRT80 mRNA and protein expression was positively correlated with the differentiation of gastric cancer (p<0.05), while KRT80 methylation was negatively associated with gastric cancer differentiation and p53 mutation (p<0.05). The expression of KRT80 mRNA was positively linked to the short survival time of gastric cancers (p<0.05). The differential genes of KRT80 mRNA were involved in ligand-receptor interaction, estrogen signal pathway, peptidase, filament and cytoskeleton, keratinocyte differentiation, vitamin D receptor, muscle contraction, and B cell-mediated immunity (p<0.05). KRT80-related genes were classified into cell adhesion and junction, cadherin binding, skin and epidermis development, and so forth (p<0.05). KRT80 knockdown suppressed proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion and epithelial-mesenchymal transition in gastric cancer cells (p<0.05). These findings indicated that up-regulated expression of KRT80 played a crucial part in gastric carcinogenesis, and might be considered as a biological marker for aggressive behaviors and poor prognosis. Its silencing might be used as an approach of target therapy for gastric cancer patients.

Water-Accelerated Transport: Vapor-Phase Nerve Agent Simulant Delivery within a Catalytic Zirconium Metal-Organic Framework as a Function of Relative Humidity.

Zirconium-based metal-organic frameworks (MOFs) are candidate materials for effective nerve agent detoxification due to their thermo- and water stability as well as high density of catalytic Zr sites. However, as high-porosity materials, most of the active sites of Zr-MOFs can only be accessed by diffusion into the crystal interior. Therefore, the transport of nerve agents in nanopores is an important factor in the catalytic performance of Zr-MOFs. Here, we investigated the transport process and mechanism of a vapor-phase nerve agent simulant, dimethyl methyl phosphonate (DMMP), through a representative Zr-MOF, NU-1008, under practical conditions of varying humidity. Confocal Raman microscopy was used to monitor the transport of DMMP vapor through individual NU-1008 crystallites, where the relative humidity (RH) of the environment was tuned to understand the impact of water. Counterintuitively, water in the MOF channels, instead of blocking DMMP transport, assists DMMP diffusion; indeed, the transport diffusivity (Dt) of DMMP in NU-1008 is one order of magnitude higher at 70% than 0% RH. To understand the mechanism, magic angle spinning NMR and molecular dynamics simulations were performed and suggested that high water content in the channels prevents DMMP from hydrogen-bonding with the nodes, allowing for faster diffusion of DMMP in the channels. The simulated self-diffusivity (Ds) of DMMP is observed to be concentration-dependent. At low loading of DMMP, Ds is higher at 70% RH than 0% RH, while at high loadings the trend reverses due to the DMMP aggregation in water and the reduction of free volume in channels.

ATF4-mediated circTDRD3 promotes gastric cancer cell proliferation and metastasis by regulating the miR-891b/ITGA2 axis and AKT signaling pathway.

BACKGROUND: Gastric cancer (GC) is a cancer of the gastrointestinal tract that is highly malignant and has poor prognosis. Circular RNAs are a class of nonclassical RNA molecules that have been determined to be involved in GC malignancy in various ways. However, the underlying function and mechanism of circTDRD3 in gastric cancer remain largely unknown. METHODS: We analyzed circTDRD3 expression in databases and verified the findings in GC cell lines and tissue specimens. A series of functional gene overexpression and knockdown assays in vivo and in vitro were carried out to investigate the role of circTDRD3 in proliferation and metastasis. Here, we revealed the role of the miR-891b/ITGA2 axis by analyzing bioinformatics datasets. Furthermore, we performed dual-luciferase, fluorescence in situ hybridization, RNA pull-down, and functional rescue experiments to examine the relationships between circTDRD3 and its interacting molecules. Western blot confirmed the positive regulatory role of circTDRD3 in the AKT signaling pathway. A promoting effect of ATF4 on circTDRD3 was determined through chromatin immunoprecipitation. RESULTS: CircTDRD3 was significantly overexpressed in GC tissues compared with adjacent benign tissue, and its expression level was positively correlated with tumor volume and lymph node metastasis. CircTDRD3 promoted GC cell proliferation and migration in vitro and in vivo. Mechanistically, circTDRD3 exerted a tumor-promoting effect by regulating the miR-891b/ITGA2 axis and AKT signaling pathway in a positive feedback manner mediated by the transcription factor ATF4. CONCLUSIONS: ATF4-mediated circTDRD3 overexpression modulates the proliferation and metastasis of GC cells through the miR-891b/ITGA2 axis in a positive feedback manner.

A perspective on the microscopic pressure (stress) tensor: History, current understanding, and future challenges.

The pressure tensor (equivalent to the negative stress tensor) at both microscopic and macroscopic levels is fundamental to many aspects of engineering and science, including fluid dynamics, solid mechanics, biophysics, and thermodynamics. In this Perspective, we review methods to calculate the microscopic pressure tensor. Connections between different pressure forms for equilibrium and nonequilibrium systems are established. We also point out several challenges in the field, including the historical controversies over the definition of the microscopic pressure tensor; the difficulties with many-body and long-range potentials; the insufficiency of software and computational tools; and the lack of experimental routes to probe the pressure tensor at the nanoscale. Possible future directions are suggested.

Two-Dimensional Energy Histograms as Features for Machine Learning to Predict Adsorption in Diverse Nanoporous Materials.

A major obstacle for machine learning (ML) in chemical science is the lack of physically informed feature representations that provide both accurate prediction and easy interpretability of the ML model. In this work, we describe adsorption systems using novel two-dimensional energy histogram (2D-EH) features, which are obtained from the probe-adsorbent energies and energy gradients at grid points located throughout the adsorbent. The 2D-EH features encode both energetic and structural information of the material and lead to highly accurate ML models (coefficient of determination R2 ∼ 0.94-0.99) for predicting single-component adsorption capacity in metal-organic frameworks (MOFs). We consider the adsorption of spherical molecules (Kr and Xe), linear alkanes with a wide range of aspect ratios (ethane, propane, n-butane, and n-hexane), and a branched alkane (2,2-dimethylbutane) over a wide range of temperatures and pressures. The interpretable 2D-EH features enable the ML model to learn the basic physics of adsorption in pores from the training data. We show that these MOF-data-trained ML models are transferrable to different families of amorphous nanoporous materials. We also identify several adsorption systems where capillary condensation occurs, and ML predictions are more challenging. Nevertheless, our 2D-EH features still outperform structural features including those derived from persistent homology. The novel 2D-EH features may help accelerate the discovery and design of advanced nanoporous materials using ML for gas storage and separation in the future.

The roles of BTG1 mRNA expression in cancers: A bioinformatics analysis.

BTG1 (B-cell translocation gene 1) may inhibit proliferation and cell cycle progression, induce differentiation, apoptosis, and anti-inflammatory activity. The goal of this study was to clarify the clinicopathological and prognostic significances of BTG1 mRNA expression and related signal pathways in cancers. Using the Oncomine, TCGA (the cancer genome atlas), xiantao, UALCAN (The University of ALabama at Birmingham Cancer data analysis Portal), and Kaplan-Meier plotter databases, we undertook a bioinformatics study of BTG1 mRNA expression in cancers. BTG1 expression was lower in gastric, lung, breast and ovarian cancer than normal tissue due to its promoter methylation, which was the opposite to BTG1 expression. BTG1 expression was positively correlated with dedifferentiation and histological grading of gastric cancer (p < 0.05), with squamous subtype and young age of lung cancer (p < 0.05), with infrequent lymph node metastasis, low TNM staging, young age, white race, infiltrative lobular subtype, Her2 negativity, favorable molecular subtyping, and no postmenopause status of breast cancer (p < 0.05), and with elder age, venous invasion, lymphatic invasion, and clinicopathological staging of ovarian cancer (p < 0.05). BTG1 expression was negatively correlated with favorable prognosis of gastric, lung or ovarian cancer patients, but the converse was true for breast cancer (p < 0.05). KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that the top signal pathways included cytokine-cytokine receptor interaction, cell adhesion molecules, chemokine, immune cell receptor and NF (nuclear factor)-κB signal pathways in gastric and breast cancer. The top hub genes mainly contained CD (cluster of differentiation) antigens in gastric cancer, FGF (fibroblast growth factor)-FGFR (FGF receptor) in lung cancer, NADH (nicotinamide adenine dinucleotide): ubiquinone oxidoreductase in breast cancer, and ribosomal proteins in ovarian cancer. BTG1 expression might be employed as a potential marker to indicate carcinogenesis and subsequent progression, even prognosis.

The clinicopathological significances and related signal pathways of BTG3 mRNA expression in cancers: A bioinformatics analysis.

B cell transposition gene 3 (BTG3) is reported to be a tumor suppressor and suppresses proliferation and cell cycle progression. This study aims to analyze the clinicopathological and prognostic significances, and signal pathways of BTG3 mRNA expression in human beings through bioinformatics analysis. We analyzed BTG3 expression using Oncomine, TCGA (the cancer genome atlas), Xiantao, UALCAN (The University of ALabama at Birmingham Cancer data analysis Portal) and Kaplan-Meier plotter databases. Down-regulated BTG3 expression was observed in lung and breast cancers, compared with normal tissues (p < 0.05), but not for gastric and ovarian cancer (p < 0.05). The methylation of BTG3 was shown to be adversely correlated with its mRNA expression (p < 0.05). BTG3 expression was higher in gastric intestinal-type than diffuse-type carcinomas, G1 than G3 carcinomas (p < 0.05), in female than male cancer patients, T1-2 than T3-4, and adenocarcinoma than squamous cell carcinoma of lung cancer (p < 0.05), in invasive ductal than lobular carcinoma, N0 than N1 and N3, TNBC (triple-negative breast cancer) than luminal and Her2+, and Her2+ than luminal cancer of breast cancer (p < 0.05), and G3 than G2 ovarian carcinoma (p < 0.05). BTG3 expression was positively related to the survival rate of gastric and ovarian cancer patients (p < 0.05), but not for breast cancer (p < 0.05). KEGG and PPI (protein-protein interaction) analysis showed that the BTG3 was involved in cell cycle and DNA replication, digestion and absorption of fat and protein, spliceosome and ribosome in cancer. BTG3 expression was positively linked to carcinogenesis, histogenesis, and aggressive behaviors, and was employed to evaluate the prognosis of cancers by regulating cell cycle, metabolism, splicing and translation of RNA.

The characteristics, tumorigenicities and therapeutics of cancer stem cells based on circRNAs.

Currently, recurrence and metastasis are still the main causes leading to the failure of various therapies for malignant tumors. In view of this, research on cancer stem cells (CSCs) has received increasing attention. CSCs are a subgroup of cancer cells with the characteristics of self-renewal, multidirectional differentiation, and immortal proliferation, and are closely related to resistance, metastasis, and recurrence. Circular RNAs (circRNAs) are a type of noncoding RNA (ncRNA) containing a covalent closed loop and are characterized by their abundance, stability, conservation, and tissue specificity. In this article, we focus on the characteristics of CSCs and review the latest research advances on the role of circRNAs in CSCs.

Can we define a unique microscopic pressure in inhomogeneous fluids?

The estimation of a microscopic pressure tensor in an adsorbed thin film on a planar surface remains a challenge in both experiment and theory. While the normal pressure is well-defined for a planar surface, the tangential pressure at a point is not uniquely defined at the nanoscale. We report a new method that allows us to calculate the local pressure tensor and its spatial integral using an arbitrary contour definition of the "virial-route" local pressure tensor. We show that by integrating the local tangential pressure over a small region of space, roughly the range of the intermolecular forces, it is possible to define a coarse-grained tangential pressure that appears to be unique and free from ambiguities in the definition of the local pressure tensor. We support our argument by presenting the results for more than ten types of contour definitions of the local pressure tensor. By defining the coarse-grained tangential pressure, we can also find the effective thickness of the adsorbed layer and, in the case of a porous material, the statistical pore width. The coarse-grained in-layer and in-pore tangential pressures are determined for Lennard-Jones argon adsorbed in realistic carbon slit pores, providing a better understanding of the pressure enhancement for strongly wetting systems.

Microscopic Pressure Tensor in Cylindrical Geometry: Pressure of Water in a Carbon Nanotube.

The microscopic pressure tensor plays an important role in understanding the mechanical stability, transport, and high-pressure phenomena of confined phases. The lack of an exact formulation to account for the long-range Coulombic contribution to the local pressure tensor in cylindrical geometries prevents the characterization of molecular fluids confined in cylindrical pores. To address this problem, we first derive the local cylindrical pressure tensor for Lennard-Jones fluids based on the Harasima (H) definition, which is expected to be compatible with the Ewald summation method. The test of the H-definition pressure equations in a homogeneous system shows that the radial and azimuthal pressure have unphysical radial dependence near the origin, while the axial pressure gives physically meaningful values. We propose an alternative contour definition that is more appropriate for cylindrical geometry and show that it leads to physically realistic results for all three pressure tensor components. With this definition, the radial and azimuthal pressures are of Irving-Kirkwood (IK) type, and the axial pressure is of Harasima type. Because of the practical interest in the axial pressure, we develop a Harasima/Ewald (H/E) method for calculating the long-range Coulombic contribution to the local axial pressure for rigid molecules. As an application, the axial pressure profile of water inside and outside a (20, 20) single-wall carbon nanotube is determined. The H/E method is compared to the IK method, which assumes a spherically truncated Coulombic potential. Detailed analysis of the pressure profile by both methods shows that the water confined in the nanotube is in a stretched state overall in the axial direction.

Reply to the 'Comment on "Pressure enhancement in carbon nanopores: a major confinement effect"' by D. van Dijk, Phys. Chem. Chem. Phys., 2020, 22, DOI: 10.1039/C9CP02890K.

In his 'Comment' van Dijk points out that the local pressure at a point r in an inhomogeneous thermodynamic system, like other thermodynamic properties, is not uniquely defined; one must make an operational definition that involves deciding how to assign the intermolecular forces between pairs of molecules to the point r. This non-uniqueness difficulty is well known, and was discussed in our paper. It was discussed in detail in the 1950 paper of Irving and Kirkwood, and in many books and papers since then. We reply to these comments, and note that an average of the local pressure over a region of space may yield a well-defined pressure. We also discuss other possible ways to quantify the adsorption compression effect near an attractive wall. van Dijk also suggests that the non-uniqueness difficulty can be avoided by using the pressure of the uniform bulk fluid in equilibrium with the pore. While this pressure is well-defined, it only reflects the intermolecular forces in the bulk phase, and gives no information about the behavior in the pore.

Modified gaphene oxide (GO) particles in peptide hydrogels: a hybrid system enabling scheduled delivery of synergistic combinations of chemotherapeutics.

The scheduled delivery of synergistic drug combinations is increasingly recognized as highly effective against advanced solid tumors. Of particular interest are composite systems that release a sequence of drugs with defined kinetics and molar ratios to enhance therapeutic effect, while minimizing the dose to patients. In this work, we developed a homogeneous composite comprising modified graphene oxide (GO) nanoparticles embedded in a Max8 peptide hydrogel, which provides controlled kinetics and molar ratios of release of doxorubicin (DOX) and gemcitabine (GEM). First, modified GO nanoparticles (tGO) were designed to afford high DOX loading and sustained release (18.9% over 72 h and 31.4% over 4 weeks). Molecular dynamics simulations were utilized to model the mechanism of DOX loading as a function of surface modification. In parallel, a Max8 hydrogel was developed to release GEM with faster kinetics and achieve a 10-fold molar ratio to DOX. The selected DOX/tGO nanoparticles were suspended in a GEM/Max8 hydrogel matrix, and the resulting composite was tested against a triple negative breast cancer cell line, MDA-MB-231. Notably, the composite formulation afforded a combination index of 0.093 ± 0.001, indicating a much stronger synergism compared to the DOX-GEM combination co-administered in solution (CI = 0.396 ± 0.034).

Conformal Sites Theory for Adsorbed Films on Energetically Heterogeneous Surfaces.

We present a conformal sites theory for a solid substrate whose surface is both geometrically and energetically heterogeneous and that interacts with an adsorbed film. The theory is based on a perturbation expansion for the grand potential of a real system with a rough surface about that of a reference system with an ideal reference surface, thus mapping the real system onto a much simpler interfacial system. The expansion is in powers of the intermolecular potential parameters, and leads to mixing rules for the potential parameters of the reference system. Grand canonical Monte Carlo simulations for the adsorption of argon at 87.3 K, carbon dioxide at 273 K, and water vapor at 298 K on heterogeneous carbon surfaces are investigated to explore the limits of applicability of the theory. Simulation results indicate that the theory works well with typical asymmetry of the potential parameters in the force field. However, care should be taken when applying the theory to strongly associating fluids and in the low-pressure region where the active surface sites play an important role. The conformal sites theory can be used to predict the adsorption properties and to characterize the solid substrate by taking advantage of the corresponding states principle. Other possible applications are also discussed.

Bottom-Up Approach to the Coarse-Grained Surface Model: Effective Solid-Fluid Potentials for Adsorption on Heterogeneous Surfaces.

Coarse-grained surface models with a low-dimension positional dependence have great advantages in simplifying the theoretical adsorption model and speeding up molecular simulations. In this work, we present a bottom-up strategy, developing a new two-dimensional (2D) coarse-grained surface model from the "bottom-level" atomistic model, for adsorption on highly heterogeneous surfaces with various types of defects. The corresponding effective solid-fluid potential consists of a 2D hard wall potential representing the structure of the surface and a one-dimensional (1D) effective area-weighted free-energy-averaged (AW-FEA) potential representing the energetic strength of the substrate-adsorbate interaction. Within the conventional free-energy-averaged (FEA) framework, an accessible-area-related parameter is introduced into the equation of the 1D effective solid-fluid potential, which allows us not only to obtain the energy information from the fully atomistic system but also to get the structural dependence of the potential on any geometric defect on the surface. Grand canonical Monte Carlo simulations are carried out for argon adsorption at 87.3 K to test the validity of the new 2D surface model against the fully atomistic system. We test four graphitic substrates with different levels of geometric roughness for the top layer, including the widely used reference solid substrate Cabot BP-280. The simulation results show that adding one more dimension to the traditional 1D surface model is essential for adsorption on the geometrically heterogeneous surfaces. In particular, the 2D surface model with the AW-FEA solid-fluid potential significantly improves the adsorption isotherm and density profile over the 1D surface model with the FEA solid-fluid potential over a wide range of pressure. The method to construct an effective solid-fluid potential for an energetically heterogeneous surface is also discussed.

High-density equation of state for a two-dimensional Lennard-Jones solid.

We present a new equation of state for a two-dimensional Lennard-Jones (2D LJ-EOS) solid at high densities, ρ2D*≥0.9. The new 2D LJ-EOS is of analytic form, consisting of a zero-temperature contribution and vibrational contributions up to and including the second anharmonic term. A detailed analysis of all contributing terms is performed. Comparisons between the 2D LJ-EOS and Monte Carlo simulation results show that the 2D LJ-EOS is very accurate over a wide range of temperatures in the high-density region. A criterion to find the temperature range over which the 2D LJ-EOS is applicable at a certain density is derived. We also demonstrate an application of the equation of state to predict an effective tangential pressure for the adsorbed contact layer near the wall in a slit-pore system. Tangential pressures predicted by this "2D-route" are found to be in qualitative agreement with those found by the more traditional virial route of Irving and Kirkwood.

Coarse-Grained Simulation of Polycation/DNA-Like Complexes: Role of Neutral Block.

Complexes formed by polycations and DNA are of great research interest because of their prospective application in gene therapy. Whereas the applications of multiblock based polycation generally exhibit promising features, a thorough understanding on the effect of neutral block incorporated in polycation is still lacking. By using coarse-grained dynamics simulation with the help of a simple model for solvent mediated interaction, we perform a theoretical study on the physicochemical properties of various polyplexes composed of a single DNA-like polyanion chain and numbers of linear polycationic chains with different modifications. By analyzing various properties, we find the hydrophobic/hydrophilic modifications of linear polycations may bring an improvement on one aspect of the properties as gene carrier but also involve a trade-off with another one. In particular, polycation with a hydrophobic middle block and a hydrophilic tail block display distinct advantages among di- and triblock linear polycations as gene carrier, while careful design of the hydrophobic block should be made to reduce the zeta potential. The simulation results are compared with available experimental data displaying good agreements.