Highly anisotropic mechanical and optical properties of 2D NbOX2 (X = Cl, Br, I) revealed by first-principle.

In the latest experimental success, NbOI2two-dimensional (2D) crystals with anisotropic electronic and optical properties have been fabricated (Adv. Mater.33 (2021), 2101505). In this work inspired by the aforementioned accomplishment, we conduct first-principles calculations to explore the mechanical, electronic, and optical properties of NbOX2(X = Cl, Br, I) nanosheets. We show that individual layers in these systems are weakly bonded, with exfoliation energies of 0.22, 0.23, and 0.24 J m-2, for the isolation of the NbOCl2, NbOBr2,and NbOI2monolayers, respectively, distinctly lower than those of the graphene. The optoelectronic properties of the single-layer, bilayer, and bulk NbOCl2, NbOBr2,and NbOI2crystals are investigated via density functional theory calculations with the HSE06 approach. Our results indicate that the layered bulk NbOCl2, NbOBr2,and NbOI2crystals are indirect gap semiconductors, with band gaps of 1.79, 1.69, and 1.60 eV, respectively. We found a slight increase in the electronic gap for the monolayer and bilayer systems due to electron confinement at the nanoscale. Our results show that the monolayer and bilayer of these novel 2D compounds show suitable valence and conduction band edge positions for visible-light-driven water splitting reactions. The first absorption peaks of these novel monolayers along the in-plane polarization are located in the visible range of light which can be a promising feature to design advanced nanoelectronics. We found that the studied 2D systems exhibit highly anisotropic mechanical and optical properties. The presented first-principles results provide a comprehensive vision about direction-dependent mechanical and optical properties of NbOX2(X = Cl, Br, I) nanosheets.

Interface Characterization Between Polyethylene/ Silica in Engineered Cementitious Composites by Molecular Dynamics Simulation.

Polyethylene is widely adopted in engineered cementitious composites to control the crack width. A clearer knowledge of the PE/concrete interfacial properties is important in developing engineered cementitious composites, which can lead to a limited crack width. Tensile failure and adhesion properties of the amorphous polyethylene/silica (PE/S) interface are investigated by molecular dynamics to interpret the PE/concrete interface. The influence of the PE chain length, the PE chain number and coupling agents applied on silica surface on the interfacial adhesion is studied. An increase of the adhesion strength of the modified silica surface by coupling agents compared with the unmodified silica is found. The failure process, density profile and potential energy evolutions of the PE/S interface are studied. The thermodynamic work of adhesion that quantifies the interfacial adhesion of the PE/S interface is evaluated. The present study helps to understand the interfacial adhesion behavior between ECC and PE, and is expected to contribute to restricting the crack width.

The generation of piezoelectricity and flexoelectricity in graphene by breaking the materials symmetries.

Graphene is a non-piezoelectric material. Engineering the piezoelectricity in graphene is possible with the help of impurities, defects and structural modifications. This study reports the mechanism of strain induced polarization and the estimation of piezoelectric and flexoelectric coefficients for graphene system. The combination of charge-dipole potential and the strong many-body potential is employed for describing the inter-atomic interactions. The breaking of symmetry in graphene material is utilized to generate the polarization. Pristine graphene, graphene with circular defect, graphene with triangular defect and trapezium-shaped graphene are considered. Molecular dynamics simulations are performed for straining the graphene atomic systems. The optimization of charge-dipole potential functions measure the polarization for these systems. Pristine and circular defect graphene systems show a constant polarization with strain. The polarization is varying with strain for a triangular defected and trapezium-shaped graphene system. The local atomic deformation produces a change in polarization with respect to the strain gradient. Estimated piezo and flexo coefficients motivate the usage of graphene in electro-mechanical devices.

Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase.

The intestinal immune system is continuously exposed to massive amounts of nanoparticles derived from food. Whether nanoparticles from plants we eat daily have a role in maintaining intestinal immune homeostasis is poorly defined. Here, we present evidence supporting our hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs). Using three mouse colitis models, our data show that orally given nanoparticles isolated from broccoli extracts protect mice against colitis. Broccoli-derived nanoparticle (BDN)-mediated activation of adenosine monophosphate-activated protein kinase (AMPK) in DCs plays a role in not only prevention of DC activation but also induction of tolerant DCs. Adoptively transferring DCs pre-pulsed with total BDN lipids, but not sulforaphane (SFN)-depleted BDN lipids, prevented DSS-induced colitis in C57BL/6 (B6) mice, supporting the role of BDN SFN in the induction of DC tolerance. Adoptively transferring AMPK+/+, but not AMPK-/-, DCs pre-pulsed with SFN prevented DSS-induced colitis in B6 mice, further supporting the DC AMPK role in SFN-mediated prevention of DSS-induced colitis. This finding could open new preventive or therapeutic avenues to address intestinal-related inflammatory diseases via activating AMPK.

Grapefruit-derived Nanovectors Delivering Therapeutic miR17 Through an Intranasal Route Inhibit Brain Tumor Progression.

The lack of access to the brain is a major obstacle for central nervous system drug development. In this study, we demonstrate the capability of a grapefruit-derived nanovector (GNV) to carry miR17 for therapeutic treatment of mouse brain tumor. We show that GNVs coated with folic acid (FA-GNVs) are enhanced for targeting the GNVs to a folate receptor-positive GL-26 brain tumor. Additionally, FA-GNV-coated polyethylenimine (FA-pGNVs) not only enhance the capacity to carry RNA, but the toxicity of the polyethylenimine is eliminated by the GNVs. Intranasal administration of miR17 carried by FA-pGNVs led to rapid delivery of miR17 to the brain that was selectively taken up by GL-26 tumor cells. Mice treated intranasally with FA-pGNV/miR17 had delayed brain tumor growth. Our results demonstrate that this strategy may provide a noninvasive therapeutic approach for treating brain-related disease through intranasal delivery.

Quantitatively controlling expression of miR-17~92 determines colon tumor progression in a mouse tumor model.

The miRNA cluster miR-17~92 targets mRNAs involved in distinct pathways that either promote or inhibit tumor progression. However, the cellular and molecular mechanisms underlying miR-17~92 cluster-mediated protumorigenic or anti-tumorigenic effects have not been studied. Herein, we determined that inhibition of colon cancer progression is dictated by quantitatively controlling expression of the miR-17~92 cluster. miR-19 in the context of the miR-17~92 cluster at medium levels promoted tumor metastasis through induction of Wnt/ß-catenin-mediated epithelial-mesenchymal transition by targeting to the tumor-suppressor gene, PTEN. However, higher levels of the miR-17~92 cluster switched from PTEN to oncogenes, including Ctnnb1 (ß-catenin) via miR-18a, which resulted in inhibition of tumor growth and metastasis. However, overexpression of Ctnnb1in tumor cells with high-level miR-17~92 did not lead to an increase in the levels of ß-catenin protein, suggesting that other factors regulated by higher levels of miR-17~92 might also contribute to inhibition of tumor growth and metastasis. Those unidentified factors may negatively regulate the production of ß-catenin protein. Collectively, the data presented in this study revealed that higher levels of miR-17~92 were a critical negative regulator for activation of the Wnt/ß-catenin pathway and could have a potential therapeutic application.

Exosome-like nanoparticles from intestinal mucosal cells carry prostaglandin E2 and suppress activation of liver NKT cells.

Regulation and induction of anergy in NKT cells of the liver can inhibit autoimmune and antitumor responses by mechanisms that are poorly understood. We investigated the effects of PGE2, delivered by intestinal, mucus-derived, exosome-like nanoparticles (IDENs), on NKT cells in mice. In this study, we demonstrate that IDENs migrate to the liver where they induce NKT cell anergy. These effects were mediated by an IDENs' PGE2. Blocking PGE2 synthesis attenuated IDENs inhibition of induction of IFN-γ and IL-4 by α-galactosylceramide (α-GalCer)-stimulated liver NKT cells in a PGE2 E-type prostanoid 2/E-type prostanoid 4 receptor-mediated manner. Proinflammatory conditions enhanced the migration of IDENs to the liver where α-GalCer and PGE2 induced NKT anergy in response to subsequent α-GalCer stimulation. These findings demonstrate that IDENs carrying PGE2 can be transferred from the intestine to the liver, where they act as immune modulators, inducing an anergic-like state of NKT cells. These reagents might be developed as therapeutics for autoimmune liver diseases.

Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit.

The gut mucosal immune system is considered to play an important role in counteracting potential adverse effects of food-derived antigens including nanovesicles. Whether nanovesicles naturally released from edible fruit work in a coordinated manner with gut immune cells to maintain the gut in a noninflammatory status is not known. Here, as proof of concept, we demonstrate that grapefruit-derived nanovesicles (GDNs) are selectively taken up by intestinal macrophages and ameliorate dextran sulfate sodium (DSS)-induced mouse colitis. These effects were mediated by upregulating the expression of heme oxygenase-1 (HO-1) and inhibiting the production of IL-1ß and TNF-α in intestinal macrophages. The inherent biocompatibility and biodegradability, stability at wide ranges of pH values, and targeting of intestinal macrophages led us to further develop a novel GDN-based oral delivery system. Incorporating methotrexate (MTX), an anti-inflammatory drug, into GDNs and delivering the MTX-GDNs to mice significantly lowered the MTX toxicity when compared with free MTX, and remarkably increased its therapeutic effects in DSS-induced mouse colitis. These findings demonstrate that GDNs can serve as immune modulators in the intestine, maintain intestinal macrophage homeostasis, and can be developed for oral delivery of small molecule drugs to attenuate inflammatory responses in human disease.

Intestinal mucus-derived nanoparticle-mediated activation of Wnt/ß-catenin signaling plays a role in induction of liver natural killer T cell anergy in mice.

UNLABELLED: The Wnt/ß-catenin pathway has been known to play a role in induction of immune tolerance, but its role in the induction and maintenance of natural killer T (NKT) cell anergy is unknown. We found that activation of the Wnt pathways in the liver microenvironment is important for induction of NKT cell anergy. We identified a number of stimuli triggering Wnt/ß-catenin pathway activation, including exogenous NKT cell activator, glycolipid α-GalCer, and endogenous prostaglandin E2 (PGE2). Glycolipid α-GalCer treatment of mice induced the expression of wnt3a and wnt5a in the liver and subsequently resulted in a liver microenvironment that induced NKT cell anergy to α-GalCer restimulation. We also found that circulating PGE2 carried by nanoparticles is stable, and that these nanoparticles are A33(+) . A33(+) is a marker of intestinal epithelial cells, which suggests that the nanoparticles are derived from the intestine. Mice treated with PGE2 associated with intestinal mucus-derived exosome-like nanoparticles (IDENs) induced NKT cell anergy. PGE2 treatment leads to activation of the Wnt/ß-catenin pathway by inactivation of glycogen synthase kinase 3ß of NKT cells. IDEN-associated PGE2 also induces NKT cell anergy through modification of the ability of dendritic cells to induce interleukin-12 and interferon-ß in the context of both glycolipid presentation and Toll-like receptor-mediated pathways. CONCLUSION: These findings demonstrate that IDEN-associated PGE2 serves as an endogenous immune modulator between the liver and intestines and maintains liver NKT cell homeostasis. This finding has implications for development of NKT cell-based immunotherapies. (HEPATOLOGY 2013).

Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5⁺ stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5⁺ stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking ß-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5⁺ stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.

Remarkably high tensile strength and lattice thermal conductivity in wide band gap oxidized holey graphene C2O nanosheet.

Recently, the synthesis of oxidized holey graphene with the chemical formula C2O has been reported (J. Am. Chem. Soc. 2024, 146, 4532). We herein employed a combination of density functional theory (DFT) and machine learning interatomic potential (MLIP) calculations to investigate the electronic, optical, mechanical and thermal properties of the C2O monolayer, and compared our findings with those of its C2N counterpart. Our analysis shows that while the C2N monolayer exhibits delocalized π-conjugation and shows a 2.47 eV direct-gap semiconducting behavior, the C2O counterpart exhibits an indirect gap of 3.47 eV. We found that while the C2N monolayer exhibits strong absorption in the visible spectrum, the initial absorption peaks in the C2O lattice occur at around 5 eV, falling within the UV spectrum. Notably, we found that the C2O nanosheet presents significantly higher tensile strength compared to its C2N counterpart. MLIP-based calculations show that at room temperature, the C2O nanosheet can exhibit remarkably high tensile strength and lattice thermal conductivity of 42 GPa and 129 W/mK, respectively. The combined insights from DFT and MLIP-based results provide a comprehensive understanding of the electronic and optical properties of C2O nanosheets, suggesting them as mechanically robust and highly thermally conductive wide bandgap semiconductors.

Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression.

Exosomes participate in intercellular communication, but most data published are based on exosomes released from in vitro cultured cells that do not communicate with neighboring cells located in the same microenvironment as the exosomal-producing cells in vivo. In this study, our data show that co-culture of leukocytes isolated from breast tumor tissue leads to uptake of fibronectin (FN) on or in the tumor exosomes (Exo(fib+)). The induction of FN and exosomal uptake is tumor tissue derived and leukocyte specific, because leukocytes isolated from the peripheral blood of naïve mice failed to induce FN uptake by tumor exosomes. Furthermore, depletion of both CD25(+) cells and Gr-1(+) cells from tumor-associated leukocytes causes a reduction of Exo(fib+), suggesting that tumor-associated CD25(+) cells and Gr-1(+) cells participate in FN production and uptake by tumor exosomes, resulting in Exo(fib+). As a result of tumor cells absorbing Exo(fib+), two major events are induced: focal adhesion kinase/Src-dependent signaling pathways are activated, and the production of proinflammatory cytokines and metalloproteinase 9 is enhanced in response to absorbing exosomes. This, in turn, enhances tumor cell invasion in vitro and in vivo. Collectively, our findings provide evidence that exosomes released from freshly excised tumor tissue cells that have communicated/interacted with immune cells gain new immune evasion capacity.

Vibration Analysis of a Unimorph Nanobeam with a Dielectric Layer of Both Flexoelectricity and Piezoelectricity.

In this study, for the first time, free and forced vibrational responses of a unimorph nanobeam consisting of a functionally graded base, along with a dielectric layer of both piezoelectricity and flexoelectricity, is investigated based on paradox-free local/nonlocal elasticity. The formulation and boundary conditions are attained by utilizing the energy method Hamilton's principle. In order to set a comparison, the formulation of a model in the framework of differential nonlocal is first presented. An effective implementation of the generalized differential quadrature method (GDQM) is then utilized to solve higher-order partial differential equations. This method can be utilized to solve the complex equations whose analytic results are quite difficult to obtain. Lastly, the impact of various parameters is studied to characterize the vibrational behavior of the system. Additionally, the major impact of flexoelectricity compared to piezoelectricity on a small scale is exhibited. The results show that small-scale flexoelectricity, rather than piezoelectricity, is dominant in electromechanical coupling. One of the results that can be mentioned is that the beams with higher nonlocality have the higher voltage and displacement under the same excitation amplitude. The findings can be helpful for further theoretical as well as experimental studies in which dielectric material is used in smart structures.

Atomistic modeling of the mechanical properties: the rise of machine learning interatomic potentials.

Since the birth of the concept of machine learning interatomic potentials (MLIPs) in 2007, a growing interest has been developed in the replacement of empirical interatomic potentials (EIPs) with MLIPs, in order to conduct more accurate and reliable molecular dynamics calculations. As an exciting novel progress, in the last couple of years the applications of MLIPs have been extended towards the analysis of mechanical and failure responses, providing novel opportunities not heretofore efficiently achievable, neither by EIPs nor by density functional theory (DFT) calculations. In this minireview, we first briefly discuss the basic concepts of MLIPs and outline popular strategies for developing a MLIP. Next, by considering several examples of recent studies, the robustness of MLIPs in the analysis of the mechanical properties will be highlighted, and their advantages over EIP and DFT methods will be emphasized. MLIPs furthermore offer astonishing capabilities to combine the robustness of the DFT method with continuum mechanics, enabling the first-principles multiscale modeling of mechanical properties of nanostructures at the continuum level. Last but not least, the common challenges of MLIP-based molecular dynamics simulations of mechanical properties are outlined and suggestions for future investigations are proposed.

Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain.

In this study, exosomes used to encapsulate curcumin (Exo-cur) or a signal transducer and activator of transcription 3 (Stat3) inhibitor, i.e., JSI124 (Exo-JSI124) were delivered noninvasively to microglia cells via an intranasal route. The results generated from three inflammation-mediated disease models, i.e., a lipopolysaccharide (LPS)-induced brain inflammation model, experimental autoimmune encephalitis and a GL26 brain tumor model, showed that mice treated intranasally with Exo-cur or Exo-JSI124 are protected from LPS-induced brain inflammation, the progression of myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE), and had significantly delayed brain tumor growth in the GL26 tumor model. Intranasal administration of Exo-cur or Exo-JSI124 led to rapid delivery of exosome encapsulated drug to the brain that was selectively taken up by microglial cells, and subsequently induced apoptosis of microglial cells. Our results demonstrate that this strategy may provide a noninvasive and novel therapeutic approach for treating brain inflammatory-related diseases.

A first-principles and machine-learning investigation on the electronic, photocatalytic, mechanical and heat conduction properties of nanoporous C5N monolayers.

Carbon nitride nanomembranes are currently among the most appealing two-dimensional (2D) materials. As a nonstop endeavor in this field, a novel 2D fused aromatic nanoporous network with a C5N stoichiometry has been most recently synthesized. Inspired by this experimental advance and exciting physics of nanoporous carbon nitrides, herein we conduct extensive density functional theory calculations to explore the electronic, optical and photocatalytic properties of the C5N monolayer. In order to examine the dynamic stability and evaluate the mechanical and heat transport properties under ambient conditions, we employ state of the art methods on the basis of machine-learning interatomic potentials. The C5N monolayer is found to be a direct band gap semiconductor, with a band-gap of 2.63 eV according to the HSE06 method. The obtained results confirm the dynamic stability, remarkable tensile strengths over 10 GPa and a low lattice thermal conductivity of ∼9.5 W m-1 K-1 for the C5N monolayer at room temperature. The first absorption peak of the single-layer C5N along the in-plane polarization is predicted to appear in the visible range of light. With a combination of high carrier mobility, appropriate band edge positions and strong absorption of visible light, the C5N monolayer might be an appealing candidate for photocatalytic water splitting reactions. The presented results provide an extensive understanding concerning the critical physical properties of the C5N nanosheets and also highlight the robustness of machine-learning interatomic potentials in the exploration of complex physical behaviors.

Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells.

In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from wild-type B6 mice also more potently inhibited T cell activation and induction of interleukin-6 and tumor necrosis factor-alpha than MDSCs isolated from the lung of MyD88 KO mice. In vitro, addition of tumor exosomes to bone marrow-derived CD11b(+)Gr-1(+) cells isolated from wild-type B6 mice resulted in more cytokine production, including tumor necrosis factor-alpha, interleukin-6, and the chemokine CCL2, than CD11b(+)Gr-1(+) cells isolated from MyD88 KO mice. Moreover, lower levels of CCL2 were observed in the lungs in MyD88 KO mice pretreated with tumor exosomes than that in wild-type mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated expansion of MDSCs and tumor metastasis.

A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.

Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects.

First-Principles Multiscale Modeling of Mechanical Properties in Graphene/Borophene Heterostructures Empowered by Machine-Learning Interatomic Potentials.

Density functional theory calculations are robust tools to explore the mechanical properties of pristine structures at their ground state but become exceedingly expensive for large systems at finite temperatures. Classical molecular dynamics (CMD) simulations offer the possibility to study larger systems at elevated temperatures, but they require accurate interatomic potentials. Herein the authors propose the concept of first-principles multiscale modeling of mechanical properties, where ab initio level of accuracy is hierarchically bridged to explore the mechanical/failure response of macroscopic systems. It is demonstrated that machine-learning interatomic potentials (MLIPs) fitted to ab initio datasets play a pivotal role in achieving this goal. To practically illustrate this novel possibility, the mechanical/failure response of graphene/borophene coplanar heterostructures is examined. It is shown that MLIPs conveniently outperform popular CMD models for graphene and borophene and they can evaluate the mechanical properties of pristine and heterostructure phases at room temperature. Based on the information provided by the MLIP-based CMD, continuum models of heterostructures using the finite element method can be constructed. The study highlights that MLIPs were the missing block for conducting first-principles multiscale modeling, and their employment empowers a straightforward route to bridge ab initio level accuracy and flexibility to explore the mechanical/failure response of nanostructures at continuum scale.