Coating tetrahedral DNA framework with endosomolytic peptides for improved stability and cytosolic delivery

DNA nanostructures have emerged as promising carriers for drug delivery.However,challenges such as low stability,poor cellular uptake efficiency,and vulnerability to lysosomal degradation still hinder their therapeutic potential.In this study,we demonstrate the coating of tetrahedral DNA frameworks(TDF)with the endosomolytic peptide L17E through electrostatic interactions to address these issues.Our findings highlight that L17E coating substantially enhances the stability of TDFs and improves their uptake efficiency into RAW264.7 cells through endocytosis and macropinocytosis.Moreover,L17E coating enables efficient endosomal release of TDFs.Finally,we employed L17E-coated TDF to deliver osteogenic growth peptide and demonstrated its potential applications in inhibiting periodontitis both in vitro and in vivo.This straightforward and cost-effective strategy holds promise for advancing the biomedical applications of DNA nanostructures.

A Parallel Algorithm for Adaptive Local Refinement of Tetrahedral Meshes Using Bisection

Local mesh refinement is one of the key steps in the implementations of adaptive finite element methods. This paper presents a parallel algorithm for distributed memory parallel computers for adaptive local refinement of tetrahedral meshes using bisection. This algorithm is used in PHG, Parallel Hierarchical Grid Chttp：//lsec. cc. ac. cn/phg/）, a toolbox under active development for parallel adaptive finite element solutions of partial differential equations. The algorithm proposed is characterized by allowing simukaneous refinement of submeshes to arbitrary levels before synchronization between submeshes and without the need of a central coordinator process for managing new vertices. Using the concept of canonical refinement, a simple proof of the independence of the resulting mesh on the mesh partitioning is given, which is useful in better understanding the behaviour of the biseetioning refinement procedure.

ALGORITHMS FOR TETRAHEDRAL NETWORK(TEN) GENERATION

The Tetrahedral Network(TEN) is a powerful 3-D vector structure in GIS, which has a lot of advantages such as simple structure, fast topological relation processing and rapid visualization. The difficulty of TEN application is automatic creating data structure. Although a raster algorithm has been introduced by some authors, the problems in accuracy, memory requirement, speed and integrity are still existent. In this paper, the raster algorithm is completed and a vector algorithm is presented after a 3-D data model and structure of TEN have been introducted. Finally, experiment, conclusion and future work are discussed.

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis

Osteoarthritis, a disorder characterized by articular cartilage deterioration, varying degrees of inflammation, and chondrocyte apoptosis, is the most common chronic joint disease. To slow or reverse its progression, inflammation should be inhibited, and chondrocyte proliferation should be promoted. Tetrahedral framework nucleic acids can be internalized by chondrocytes(even inflammatory chondrocytes) and can enhance their proliferation and migration. Wogonin, a naturally occurring flavonoid,suppresses oxidative stress and inhibits inflammation. In this study, tetrahedral framework nucleic acids were successfully selfassembled and used to load wogonin. We confirmed the effective formation of tetrahedral framework nucleic acid/wogonin complexes by dynamic light scattering, zeta potential analysis, transmission electron microscopy, and fluorescence spectrophotometry. Tetrahedral framework nucleic acids, wogonin, and especially tetrahedral framework nucleic acid/wogonin complexes effectively alleviated inflammation in vitro and in vivo and prevented cartilage destruction. In addition, these materials remarkably downregulated the expression of inflammatory mediators and matrix metalloproteinases, upregulated chondrogenic markers, and promoted tissue inhibitor of metalloproteinase 1 and B-cell lymphoma 2 expression. In vivo, after treatment with tetrahedral framework nucleic acid/wogonin complexes, the bone mineral density in regenerated tissues was much higher than that found in the untreated groups. Histologically, the complexes enhanced new tissue regeneration, significantly suppressed chondrocyte apoptosis, and promoted chondrogenic marker expression. They also inhibited cell apoptosis, increased chondrogenic marker expression, and suppressed the expression of inflammatory mediators in osteoarthritis. Therefore, we believe that tetrahedral framework nucleic acid/wogonin complexes can be used as an injectable form of therapy for osteoarthritis.

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids(t FNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, t FNAs have been widely applied in the biomedical field as threedimensional DNA nanomaterials. Surprisingly, t FNAs exhibit positive effects on cellular biological behaviors and tissue regeneration,which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity,t FNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization,intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic t FNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic t FNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone,cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.

Assessment of k–ε models using tetrahedral grids to describe the turbulent flow field of a PBT impeller and validation through the PIV technique

In turbulence modeling, the RNG and Realizable models have important improvements in the turbulent production and dissipation terms in comparison to the Standard. The selection of the appropriate turbulence model has an impact on the convergence and solution in STRs, and they are used in mixing, multiphase modeling or as starting solution of transient models as DES and LES. Although there are several studies with the pitched blade turbine(PBT) impeller, most of them used the Standard model as representative of all k–ε models, using structured hexahedral grids composed of low number of cells, and in some cases under axial symmetry assumptions.Accordingly, in this work the assessment of the Standard, RNG and Realizable models to describe the turbulent flow field of this impeller, using the Multiple Reference Frame(MRF) and Sliding Mesh(SM) approaches with tetrahedral domains in dense grids, is presented. This kind of cell elements is especially suitable to reproduce complex geometries. Flow velocities and turbulent parameters were verified experimentally by PIV and torque measurements. The three models were capable of predicting fairly the pumping number, the power number based on torque, and velocities. Although the RNG improved the predictions of the turbulent kinetic energy and dissipation rate, the Realizable model presented better performance for both approaches. All models failed in the prediction of the total dissipation rate, and a dependence of its value on the number of cells for the MRF was found.

Effect of Substrate Bias on Microstructure and Properties of Tetrahedral Amorphous Carbon Films

The microstructure and properties of tetrahedral amorphous carbon (ta-C) films deposited by the filtered cathodic vacuum arc technology has been investigated by visible Raman spectroscopy, AFM and Nano-indentor. The Raman spectra have been fitted with a single skewed Lorentzian lineshape described by BWF function defining coupling coefficient, which characterizes the degree of asymmetry and is correlated with the sp3 content. When the substrate bias is -80 V, the sp3 content is the most and simultaneously the coupling coefficient is the least, following with the minimum root mean square surface roughness (Rq=0.23 nm) and the highest hardness (51.49 GPa), Young′s modulus (512.39 GPa), and critical scratching load (11.72 mN). As the substrate bias is increased or decreased, the sp3 content and other properties lower correspondingly.

Optical Properties of Tetrahedral Amorphous Carbon Films and Their Potential for Lab-on-a-Chip

In this study, tetrahedral amorphous carbon (ta-C) films with thicknesses between several 100 nm and several micrometers have been deposited onto polished tungsten carbide and steel substrates by pulsed laser deposition (PLD) using an excimer laser (248 nm wavelength). We investigate the optical properties (e.g. the refractive index (n) and extinction coefficient (k) in the visible and near-infrared wavelength range) of these layers in dependence of the used laser ablation fluence on the target. It is shown that n of ~2000 nm thick ta-C films can be tuned, depending on the sp3-content, between n = 2.5 and 2.8 at a wavelength of 632 nm. Besides of this k reduces with the sp3-content and is as low as 0.03 at sp3-contents of more than 75%. We proof that this gives the opportunity to prepare coating with tailored optical properties. Furthermore, it is shown that the ta-C films have low background fluorescence in the wavelengths range of 380 - 750 nm, which make this thin films attractive for certain optical, medical and biotechnological applications. We present for the first time that one possible application is the use in Lab-on-a-Chip-systems (LOC). Within these systems, the ultrasensitive detection of fluorescence markers and dyes is a challenge. In order to increase the signal-to-noise-ratio, a setup was developed, that used the specific optical properties of ta-C films produced by PLD. We used the ta-C film as an integrated reflector that combined low background fluorescence, a low reflectivity at the excitation wavelength and the high reflectivity at the emission wavelength. We prove that this setup improves the detection of fluorescence photons.

SYNTHESES OF TETRAHEDRAL METAL CLUSTER COMPOUNDS

The carbyne compound [Br(CO)_2(Py)_2Mo(≡CC_6H_5)] (Py=pyridine) (1a) reacts with Co_2 (CO)_8, Fe_2(CO)_9 and Mn_2 (CO)_(10) to give tetrahedral tri-metal cluster compounds Co_2Mo(μ_3-CC_6H_5)Br(CO)_8(Py)_2 (2), Fe_2Mo(μ_3-CC_6H_5) Br(CO)_9(Py)_2 (3) and Mn_2Mo(μ_3-CC_6H_5)Br(CO)_(10) (Py)_2 (4) respectively. Tri-metal cluster compound Co_2Mo(μ_3-CC_6H_5)Br(CO)_8-(bipy) (bipy=α,α'dipyridyl) (5) is prepared in a similar reaction sequence from [Br(CO)_2(bipy)Mo(≡CC_6H_5)] (1b) and Co_2(CO)_8. IR, ~1H and ^(13)C NMR spectral data of these compounds are reported and discussed. The crystal structure of compound (5) has been determined by X-ray diffraction.

Application of High Performance Liquid Chromatography to Separation of Novel Chiral Tetrahedral Heterometal Clusters

A series of novel chiral tetrahedral heterometal clusters have firstly been separated on cellulose tris-(3,5-dimethylphenylcarbamate) stationary phase by high performance liquid chrom-atography, using hexane as the mobile phase with various alcohols as modifiers.

ENHANCING ADHESION OF TETRAHEDRAL AMORPHOUS CARBON FILMS

Objective The high energy ion bombardment technique is applied to enhancing the adhesion of the tetrahedral amorphous carbon (TAC) films deposited by the filtered cathode vacuum arc (FCVA). Methods The abrasion method, scratch method, heating and shaking method as well as boiling salt solution method is used to test the adhesion of the TAC films on various material substrates. Results The test results show that the adhesion is increased as the ion bombardment energy increases. However, if the bombardment energy were over the corresponding optimum value, the adhesion would be enhanced very slowly for the harder material substrates and drops quickly, for the softer ones. Conclusion The optimum values of the ion bombardment energy are larger for the harder materials than that for the softer ones.

An h-Adaptivity DG Method on Locally Curved Tetrahedral Mesh for Solving Compressible Flows

For the numerical simulation of compressible flows,normally different mesh sizes are expected in different regions.For example,smaller mesh sizes are required to improve the local numerical resolution in the regions where the physical variables vary violently(for example,near the shock waves or in the boundary layers)and larger elements are expected for the regions where the solution is smooth.h-adaptive mesh has been widely used for complex flows.However,there are two difficulties when employing h-adaptivity for high-order discontinuous Galerkin(DG)methods.First,locally curved elements are required to precisely match the solid boundary,which significantly increases the difficulty to conduct the"refining"and"coarsening"operations since the curved information has to be maintained.Second,h-adaptivity could break the partition balancing,which would significantly affect the efficiency of parallel computing.In this paper,a robust and automatic h-adaptive method is developed for high-order DG methods on locally curved tetrahedral mesh,for which the curved geometries are maintained during the h-adaptivity.Furthermore,the reallocating and rebalancing of the computational loads on parallel clusters are conducted to maintain the parallel efficiency.Numerical results indicate that the introduced h-adaptive method is able to generate more reasonable mesh according to the structure of flow-fields.

Quality Improvement Algorithm for Tetrahedral Mesh Based on Optimal Delaunay Triangulation

The concept of optimal Delaunay triangulation (ODT) and the corresponding error-based quality metric are first introduced. Then one kind of mesh smoothing algorithm for tetrahedral mesh based on the concept of ODT is examined. With regard to its problem of possible producing illegal elements, this paper proposes a modified smoothing scheme with a constrained optimization model for tetrahedral mesh quality improvement. The constrained optimization model is converted to an unconstrained one and then solved by integrating chaos search and BFGS (Broyden-Fletcher-Goldfarb-Shanno) algorithm efficiently. Quality improvement for tetrahedral mesh is finally achieved by alternately applying the presented smoothing scheme and re-triangulation. Some testing examples are given to demonstrate the effectiveness of the proposed approach.

Open Volumetric Mesh-An Efficient Data Structure for Tetrahedral and Hexahedral Meshes

This work introduces a scalable and efficient topological structure for tetrahedral and hexahedral meshes. The design of the data structure aims at maximal flexibility and high performance. It provides a high scalability by using hierarchical representa-tions of topological elements. The proposed data structure is array-based, and it is a compact representation of the half-edge data structure for volume elements and half-face data structure for volumetric meshes. This guarantees constant access time to the neighbors of the topological elements. In addition, an open-source implementation named Open Volumetric Mesh （OVM） of the pro-posed data structure is written in C＋＋ using generic programming concepts.

Un-thorough Delaunay Approach for Tetrahedral Mesh Generation

An integrated tetrahedrization algorithm in 3D domain which combines the Delaunay tetrahedral method with un-Delaunay tetrahedral method is described. The algorithm was developed by constructing Delaunay Tetrahedrons from a scattered point set, recovering boundaries using Delaunay and un-Delaunay method, inserting additional nodes in unsuitable tetrahedrons, optimizing tetrahedrons and smoothing the tetrahedral mesh with the 2D-3D Laplacian method. The algorithm has been applied to the injection molding CAE preprocessing.

A novel mesenchymal stem cell-targeting dual-miRNA delivery system based on aptamer-functionalized tetrahedral framework nucleic acids:Application to endogenous regeneration of articular cartilage

Articular cartilage injury(ACI)remains one of the key challenges in regenerative medicine,as current treatment strategies do not result in ideal regeneration of hyaline-like cartilage.Enhancing endogenous repair via micro-RNAs(miRNAs)shows promise as a regenerative therapy.miRNA-140 and miRNA-455 are two key and promising candidates for regulating the chondrogenic differentiation of mesenchymal stem cells(MSCs).In this study,we innovatively synthesized a multifunctional tetrahedral framework in which a nucleic acid(tFNA)-based targeting miRNA codelivery system,named A-T-M,was used.With tFNAs as vehicles,miR-140 and miR-455 were connected to and modified on tFNAs,while Apt19S(a DNA aptamer targeting MSCs)was directly integrated into the nanocomplex.The relevant results showed that A-T-M efficiently delivered miR-140 and miR-455 into MSCs and subsequently regulated MSC chondrogenic differentiation through corresponding mechanisms.Interestingly,a synergistic effect between miR-140 and miR-455 was revealed.Furthermore,A-T-M successfully enhanced the endogenous repair capacity of articular cartilage in vivo and effectively inhibited hypertrophic chondrocyte formation.A-T-M provides a new perspective and strategy for the regeneration of articular cartilage,showing strong clinical application value in the future treatment of ACI.

Research advances of tetrahedral framework nucleic acid-based systems in biomedicine

This article reviews the latest research advances of tetrahedral framework nucleic acid(t FNA)-based systems in their fabrication,modification,and the potential applications in biomedicine.TFNA arises from the synthesis of four single-stranded DNA chains.Each chain contains brief sequences that complement those found in the other three,culminating in the creation of a pyramid-shaped nanostructure of approximately 10 nanometers in size.The first generation of t FNA demonstrates inherent compatibility with biological systems and the ability to permeate cell membrane effectively.These attributes translate into remarkable capabilities for regulating various cellular biological processes,fostering tissue regeneration,and modulating immune responses.The subsequent evolution of t FNA introduces enhanced adaptability and a relatively higher degree of biological stability.This advancement encompasses structural modifications,such as the addition of functional domains at the vertices or side arms,integration of low molecular weight pharmaceuticals,and the implementation of diverse strategies aimed at reversing multi-drug resistance in tumor cells or microorganisms.These augmentations empower t FNA-based systems to be utilized in different scenarios,thus broadening their potential applications in various biomedical fields.

Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell

Diabetes mellitus considerably affects bone marrow mesenchymal stem cells(BMSCs),for example,by inhibiting their proliferation and differentiation potential,which enhances the difficulty in endogenous bone regeneration.Hence,effective strategies for enhancing the functions of BMSCs in diabetes have farreaching consequences for bone healing and regeneration in diabetes patients.Tetrahedral framework nucleic acids(tFNAs)are nucleic acid nanomaterials that can autonomously enter cells and regulate their behaviors.In this study,we evaluated the effects of tFNAs on BMSCs from diabetic rats.We found that tFNAs could promote the proliferation,migration,and osteogenic differentiation of BMSCs from rats with type 2 diabetes mellitus,and inhibited cell senescence and apoptosis.Furthermore,tFNAs effectively scavenged the accumulated reactive oxygen species and activated the suppressed protein kinase B(Akt)signaling pathway.Overall,we show that tFNAs can recover the proliferation and osteogenic potential of diabetic BMSCs by alleviating oxidative stress and activating Akt signaling.The study provides a strategy for endogenous bone regeneration in diabetes and also paves the way for exploiting DNA-based nanomaterials in regenerative medicine.

Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis

Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.