Therapeutic effect and study of human umbilical cord blood mononuclear cells in patients with ischaemic bowel disease.

Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.

Phantom study of a self-shielded X-ray bone age assessment instrument against scattered radiation in children.

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.

Framework Nucleic Acids-Based VEGF Signaling Activating System for Angiogenesis: A Dual Stimulation Strategy.

Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor-related signaling. In this study, based on the conventional single-stranded DNA self-assembly into tetrahedral framework nucleic acids (tFNAs), the Apt02 nucleic acid aptamer and dimethyloxallyl glycine (DMOG) small molecule are integrated into a complex via a template-based click chemistry reaction and toehold-mediated strand displacement reaction. Thus, being able to simulate the VEGF (vascular endothelial growth factor) function and stabilize HIF (hypoxia-inducible factor), a functional whole is constructed and applied to angiogenesis. Cellular studies demonstrate that the tFNAs-Apt02 complex (TAC) has a conspicuous affinity to human umbilical vein endothelial cells (HUVECs). Further incubation with DMOG yields the tFNAs-Apt02-DMOG complex (TACD), which promotes VEGF secretion, in vitro blood vessel formation, sprouting, and migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating the VEGF/VEGFR and HIF signaling pathways. Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood-vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field.

Hemodynamic Effects of Tortuosity and Stenosis in Superficial Temporal Artery-Middle Cerebral Artery Bypass for Moyamoya Disease.

BACKGROUND: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery has been widely adopted in treating moyamoya disease (MMD). Geometric variations including high tortuosity and stenosis exist in many cases, but the hemodynamic effects have not been comprehensively evaluated. We aim to evaluate the hemodynamic effects of bypass geometry variations based on patient-specific data. METHODS: In total, 17 patients with MMD who underwent STA-MCA bypass surgery with highly tortuous bypass geometry were included. For each patient, the original 3-dimensional structure of STA-MCA bypass was reconstructed from clinical imaging data. The bypass structure was virtually improved by removing the tortuosity and stenosis. Computational fluid dynamics simulation was performed on both bypass structures under identical patient-specific condition. The simulated hemodynamic parameters of the bypass and its distal branches were compared between the original and virtually improved bypass geometries in all cases using paired t-test or Wilcoxon signed-rank test. The changes of hemodynamic parameters were compared between the cases with and without mild-to-moderate stenosis (44.0-70.3% in diameter) in the bypass using t-test or Mann-Whitney U test. RESULTS: The virtual improvement of bypass geometry significantly increased the flow rate of the bypass and its distal branches (P < 0.05) and decreased the transcranial flow resistance (P < 0.05). The hemodynamic changes in cases with stenosis removal were significantly greater than those without stenosis (P < 0.05). CONCLUSIONS: High tortuosity and stenosis can significantly change the hemodynamics of STA-MCA bypass, and the optimization of bypass geometry deserves further consideration.

MicroRNA-29c-tetrahedral framework nucleic acids: Towards osteogenic differentiation of mesenchymal stem cells and bone regeneration in critical-sized calvarial defects.

Certain miRNAs, notably miR29c, demonstrate a remarkable capacity to regulate cellular osteogenic differentiation. However, their application in tissue regeneration is hampered by their inherent instability and susceptibility to degradation. In this study, we developed a novel miR29c delivery system utilising tetrahedral framework nucleic acids (tFNAs), aiming to enhance its stability and endocytosis capability, augment the efficacy of miR29c, foster osteogenesis in bone marrow mesenchymal stem cells (BMSCs), and significantly improve the repair of critical-sized bone defects (CSBDs). We confirmed the successful synthesis and biocompatibility of sticky ends-modified tFNAs (stFNAs) and miR29c-modified stFNAs (stFNAs-miR29c) through polyacrylamide gel electrophoresis, microscopy scanning, a cell counting kit-8 assay and so on. The mechanism and osteogenesis effects of stFNAs-miR29c were explored using immunofluorescence staining, western blotting, and reserve transcription quantitative real-time polymerase chain reaction. Additionally, the impact of stFNAs-miR29c on CSBD repair was assessed via micro-CT and histological staining. The nano-carrier, stFNAs-miR29c was successfully synthesised and exhibited exemplary biocompatibility. This nano-nucleic acid material significantly upregulated osteogenic differentiation-related markers in BMSCs. After 2 months, stFNAs-miR29c demonstrated significant bone regeneration and reconstruction in CSBDs. Mechanistically, stFNAs-miR29c enhanced osteogenesis of BMSCs by upregulating the Wnt signalling pathway, contributing to improved bone tissue regeneration. The development of this novel nucleic acid nano-carrier, stFNAs-miR29c, presents a potential new avenue for guided bone regeneration and bone tissue engineering research.

Tetrahedral DNA loaded siCCR2 restrains M1 macrophage polarization to ameliorate pulmonary fibrosis in chemoradiation-induced murine model.

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.

Digital workflow in the design of individualized emergence profiles of implant restorations based on the contralateral tooth.

PURPOSE: To describe a novel digital design technique for creating an individualized emergence profile for implant restoration based on the contralateral tooth. METHODS: Cone beam computed tomography (CBCT) data were used to accurately obtain a three-dimensional (3D) model of the contralateral tooth, which was mirror-flipped to design the emergence profile. The emergence profile was further divided into critical and subcritical areas; the critical area precisely replicated the mirror-flipped 3D model, whereas the subcritical area featured a slight concavity on the buccal side, flatness on the lingual side, and slight convexity on the mesial and distal surfaces. Subsequently, a milling machine was used to fabricate healing abutments with individualized emergence profiles. The design of the definitive restoration completely duplicated the emergence profile of the individualized healing abutment and was fabricated using a milling machine. CONCLUSIONS: This technical procedure presents an alternative novel method for designing the emergence profiles of implant restorations, with the potential to improve esthetics and functions as well as to maintain the long-term stability of peri-implant soft and hard tissues.

Visual treatment objective-based lateral esthetics preview for implant-supported reconstruction in terminal dentition with proclined maxillary incisors.

PATIENT: A 67-year-old woman presented with severe periodontitis-induced terminal dentition and proclined maxillary incisor. Three-dimensional facial esthetics-driven computer-assisted virtual tooth rearrangement was performed for implant-supported full-arch reconstruction. The digital workflow combines facial and spiral computed tomography (CT) scans to generate a virtual patient for three-dimensional (3D) facial analysis and obtain a visual treatment objective (VTO)-based lateral esthetic preview for virtual teeth rearrangement. Subsequently, this printed interim denture performed well in functionalization and esthetics, acted as a transitional removable denture, radiological template, and implant-supported interim denture, and guided the design of the final restoration. DISCUSSION: Conventional methods for lateral esthetic preview, such as traditional wax rim try-in, confront difficulties in the treatment of terminal dentition, especially in the presence of proclined maxillary incisors. However, currently available software that aids information fusion and facial analysis can accurately predict soft-to-hard tissue movement and efficiently guide virtual tooth rearrangement for implant-supported full-arch reconstruction. CONCLUSIONS: The use of VTO-based lateral esthetic preview for implant-supported reconstruction improves pre- and postoperative information transfer accuracy and doctor-patient communication efficiency.

A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy.

As a major late complication of diabetes, diabetic peripheral neuropathy (DPN) is the primary reason for amputation. Nevertheless, there are no wonder drugs available. Regulating dysfunctional mitochondria is a key therapeutic target for DPN. Resveratrol (RSV) is widely proven to guard mitochondria, yet the unsatisfactory bioavailability restricts its clinical application. Tetrahedral framework nucleic acids (tFNAs) are promising carriers due to their excellent cell entrance efficiency, biological safety, and structure editability. Here, RSV was intercalated into tFNAs to form the tFNAs-RSV complexes. tFNAs-RSV achieved enhanced stability, bioavailability, and biocompatibility compared with tFNAs and RSV alone. With its treatment, reactive oxygen species (ROS) production was minimized and reductases were activated in an in vitro model of DPN. Besides, respiratory function and adenosine triphosphate (ATP) production were enhanced. tFNAs-RSV also exhibited favorable therapeutic effects on sensory dysfunction, neurovascular deterioration, demyelination, and neuroapoptosis in DPN mice. Metabolomics analysis revealed that redox regulation and energy metabolism were two principal mechanisms that were impacted during the process. Comprehensive inspections indicated that tFNAs-RSV inhibited nitrosation and oxidation and activated reductase and respiratory chain. In sum, tFNAs-RSV served as a mitochondrial nanoguard (mito-guard), representing a viable drilling target for clinical drug development of DPN.

Hard tissue stability outside the buccal bone arch contour after guided bone regeneration in the anterior maxilla: A retrospective cohort radiographic study.

OBJECTIVES: To radiographically evaluate the stability of the bone substitute augmented outside the buccal bony arch contour in the maxillary esthetic zone. MATERIALS AND METHODS: Patients who missed a single anterior tooth and received simultaneous GBR in implant surgery were included. The contralateral homonymous area of the implant site was horizontally mirrored as the individual bone arch contour. According to the relative position of the postoperative buccal grafts and bone arch contour at the implant shoulder, 62 patients were allocated into the outside-contour (OC) and inside-contour (IC) groups. Cone-beam computed tomography was performed before surgery, after implant insertion, before re-entry surgery, and at follow-up. The profilometric changes of the buccal bone plate were analyzed via the bone distance to the mirrored bony contour. RESULTS: At the implant shoulder, the bone distance in the OC group was higher than that in the IC group, with statistically significant differences at re-entry surgery and follow-up. However, the bone grafts outside the bone arch contour were reduced into the contour after remodeling and showed more bone resorption than the IC group. At other vertical levels below the implant shoulder, bony grafting of overcontour 1-2 mm range was favorable to regenerate stable bone plates reaching the individual contour at follow-up. CONCLUSIONS: The overaugmented bone outside the buccal bone arch contour tended to remodel into the original contour, which indicates that the anterior bone arch contour is worthy of careful observation for deciding buccolingual implant position and bone augmentation width.

Minimally invasive techniques for lateral maxillary sinus floor elevation: small lateral window and one-stage surgery-a 2-5-year retrospective study.

This study aimed to introduce a minimally invasive technique for maxillary sinus floor elevation using the lateral approach (lSFE) and to determine the factors that influence the stability of the grafted area in the sinus cavity. Thirty patients (30 implants) treated with lSFE using minimally invasive techniques from 2015 to 2019 were included in the study. Five aspects of the implant (central, mesial, distal, buccal, and palatal bone heights [BHs]) were measured using cone-beam computed tomography (CBCT) before implant surgery, immediately after surgery (T0), 6 months after surgery (T1), and at the last follow-up visit (T2). Patients' characteristics were collected. A small bone window (height, (4.40 ± 0.74) mm; length, (6.26 ± 1.03) mm) was prepared. No implant failed during the follow-up period (3.67 ± 1.75) years. Three of the 30 implants exhibited perforations. Changes in BH of the five aspects of implants showed strong correlations with each other and BH decreased dramatically before second-stage surgery. Residual bone height (RBH) did not significantly influence BH changes, whereas smoking status and type of bone graft materials were the potentially influential factors. During the approximate three-year observation period, lSFE with a minimally invasive technique demonstrated high implant survival rate and limited bone reduction in grafted area. In conclusion, lSFE using minimally invasive techniques was a viable treatment option. Patients who were nonsmokers and whose sinus cavity was filled with deproteinized bovine bone mineral (DBBM) had significantly limited bone resorption in grafted area.

Effects of Puerarin-Loaded Tetrahedral Framework Nucleic Acids on Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is recognized as a common refractory orthopedic disease that causes severe pain and poor quality of life in patients. Puerarin (Pue), a natural isoflavone glycoside, can promote osteogenesis and inhibit apoptosis of bone mesenchymal stem cells (BMSCs), demonstrating its great potential in the treatment of osteonecrosis. However, its low aqueous solubility, fast degradation in vivo, and inadequate bioavailability, limit its clinical application and therapeutic efficacy. Tetrahedral framework nucleic acids (tFNAs) are promising novel DNA nanomaterials in drug delivery. In this study, tFNAs as Pue carriers is used and synthesized a tFNA/Pue complex (TPC) that exhibited better stability, biocompatibility, and tissue utilization than free Pue. A dexamethasone (DEX)-treated BMSC model in vitro and a methylprednisolone (MPS)-induced ONFH model in vivo is also established, to explore the regulatory effects of TPC on osteogenesis and apoptosis of BMSCs. This findings showed that TPC can restore osteogenesis dysfunction and attenuated BMSC apoptosis induced by high-dose glucocorticoids (GCs) through the hedgehog and Akt/Bcl-2 pathways, contributing to the prevention of GC-induced ONFH in rats. Thus, TPC is a promising drug for the treatment of ONFH and other osteogenesis-related diseases.

Tetrahedral framework nucleic acid loaded with glabridin: A transdermal delivery system applicated to anti-hyperpigmentation.

Topical application of tyrosinase inhibitors, such as hydroquinone and arbutin, is the most common clinical treatment for hyperpigmentation. Glabridin (Gla) is a natural isoflavone that inhibits tyrosinase activity, free radical scavenging, and antioxidation. However, its water solubility is poor, and it cannot pass through the human skin barrier alone. Tetrahedral framework nucleic acid (tFNA), a new type of DNA biomaterial, can penetrate cells and tissues and can be used as carriers to deliver small-molecule drugs, polypeptides, and oligonucleotides. This study aimed to develop a compound drug system using tFNA as the carrier to transport Gla and deliver it through the skin to treat pigmentation. Furthermore, we aimed to explore whether tFNA-Gla can effectively alleviate the hyperpigmentation caused by increased melanin production and determine whether tFNA-Gla exerts substantial synergistic effects during treatment. Our results showed that the developed system successfully treated pigmentation by inhibiting regulatory proteins related to melanin production. Furthermore, our findings showed that the system was effective in treating epidermal and superficial dermal diseases. The tFNA-based transdermal drug delivery system can thus develop into novel, effective options for non-invasive drug delivery through the skin barrier.

Expression and correlation of the Pi3k/Akt pathway and VEGF in oral submucous fibrosis.

Oral submucous fibrosis (OSF) has a high incidence in Asia countries, but its underlying molecular mechanism was not exploited completely. In this research, we investigated the expression of the phosphatidyl inositol 3-kinase (Pi3k)/protein kinase B (Akt) pathway and vascular endothelial growth factor (VEGF) in oral submucosal fibrosis, explore the correlation between the Pi3k/Akt pathway and VEGF, and identify the mechanisms involved in OSF. The pathological changes and fibrosis stages of OSF tissues (n = 30, 10 each of early, moderate and advanced OSF) were determined using Haematoxylin-eosin staining (HE) and Masson staining, respectively. Collagen type I (Col-I), Pi3k, Akt, VEGF, TGF-ß and p-Akt expression was detected using immunohistochemistry, qPCR and WB. The correlation between Pi3k, Akt and VEGF was analysed. Col-I expression increased as OSF progressed. However, their expression was downregulated in normal and moderate to advanced OSF tissues. VEGF expression positively correlated with Pi3k and Akt expression. VEGF expression correlated positively and negatively with the Pi3k inhibitor, LY294002 below and above a concentration of 10 µM, respectively. VEGF expression correlated positively with the Pi3k/Ak activator, IGF-1. Due to the synergistic effect between Pi3k/Akt pathway and VEGF on OSF lesions and fibrosis process, targeted Pi3k/Akt pathway regulation can induce VEGF expression and improve ischemia, ultimately treating OSF.

The nano-windmill exerts superior anti-inflammatory effects via reducing choline uptake to inhibit macrophage activation.

Macrophages' activation plays a central role during the development and progression of inflammation, while the regulation of metabolic reprogramming of macrophages has been recently identified as a novel strategy for anti-inflammatory therapies. Our previous studies have found that tetrahedral framework nucleic acid (tFNA) plays a mild anti-inflammatory effect by inhibiting macrophage activation, but the specific mechanism remains unclear. Here, by metabolomics and RNA sequencing, choline uptake is identified to be significantly repressed by decreased slc44a1 expression in tFNA-treated activated macrophages. Inspired by this result, combined with the excellent delivery capacities of tFNA, siR-slc44a1 is loaded into the tFNA to develop a new tFNA-based small interfering RNA (siRNA) delivery system named 'nano-windmill,' which exhibits a synergetic role by targeting slc44a1, finally blowing up the anti-inflammatory effects of tFNA to inhibit macrophages activation via reducing choline uptake. By confirming its anti-inflammatory effects in chronic (periodontitis) and acute (sepsis) inflammatory disease, the tFNA-based nanomedicine developed for inflammatory diseases may provide broad prospects for tFNA upgrading and various biological applications such as anti-inflammatory.

High-Temperature Mechanical and Dynamical Properties of γ-(U,Zr) Alloys.

High-temperature body-centered cubic (BCC) γ-U is effectively stablized by γ-(U,Zr) alloys that also make it feasible to use it as a nuclear fuel. However, relatively little research has focused on γ-(U,Zr) alloys due to their instability at room temperature. The effect of Zr composition on its mechanical properties is not clear yet. Herein, we perform molecular dynamics simulations to investigate the mechanical and dynamical stabilities of γ-(U,Zr) alloys under high temperatures, and we calculate the corresponding lattice constants, various elastic moduli, Vickers hardness, Debye temperature, and dynamical structure factor. The results showed that γ-U, ß-Zr, and γ-(U,Zr) are all mechanically and dynamically stable at 1200 K, which is in good agreement with the previously reported high-temperature phase diagram of U-Zr alloys. We found that the alloying treatment on γ-U with Zr can effectively improve its mechanical strength and melting points, such as Vickers hardness and Debye temperature, making it more suitable for nuclear reactors. Furthermore, the Zr concentrations in γ-(U,Zr) alloys have an excellent effect on these properties. In addition, the dynamical structure factor reveals that γ-U shows different structural features after alloying with Zr. The present simulation data and insights could be significant for understanding the structures and properties of UZr alloy under high temperatures.

DNA-based Nanomaterials in the Immunotherapy.

BACKGROUND: Nucleic acid is a genetic material that shows great potential in a variety of biological applications. With the help of nanotechnology, the fabrication of DNA-based nanomaterials has emerged. From genetic DNA to non-genetic functional DNA, from single-layer and flat structure to multi-layer and complex structure, and from two-dimensional to three-dimensional structure, DNA-based nanomaterials have been greatly developed, bringing significant changes to our lives. In recent years, the research of DNA-based nanomaterials for biological applications has developed rapidly. METHODS: We extensively searched the bibliographic database for a research article on nanotechnology and immunotherapy and further discussed the advantages and drawbacks of current DNA-based nanomaterials in immunotherapy. By comparing DNA-based nanomaterials with traditional biomaterials applied in immunotherapy, we found that DNA-based nanomaterials are a promising candidate material in Immunotherapy. RESULTS: Due to the unrivaled editability and biocompatibility, DNA-based nanomaterials are not only investigated as therapeutic particles to influence cell behavior but also as drug delivery systems to treat a variety of diseases. Moreover, when DNA-based nanomaterials are loaded with therapeutic agents, including chemical drugs and biomolecules, which significantly enhance the therapeutic effects, DNA-based nanomaterials have great potential in immunotherapy. CONCLUSION: This review summarizes the structural development history of DNA-based nanomaterials and their biological applications in immunotherapy, including the potential treatment of cancer, autoimmune diseases, and inflammatory diseases.

Tetrahedral framework nucleic acid nanomaterials reduce the inflammatory damage in sepsis by inhibiting pyroptosis.

Sepsis is a highly lethal condition and is caused by the dysregulation of the body's immune response to infection. Indeed, sepsis remains the leading cause of death in severely ill patients, and currently, no effective treatment is available. Pyroptosis, which is mainly activated by cytoplasmic danger signals and eventually promote the release of the pro-inflammatory factors, is a newly discovered programmed cell death procedure that clears infected cells while simultaneously triggering an inflammatory response. Increasing evidence indicates that pyroptosis participates in the development of sepsis. As a novel DNA nanomaterial, tetrahedral framework nucleic acids (tFNAs) characterized by its unique spatial structure, possess an excellent biosafety profile and can quickly enter the cell to impart anti-inflammatory and anti-oxidation effects. In this study, the roles of tFNAs in the in vitro model of macrophage cell pyroptosis and in the in vivo model of septic mice were examined, and it was found that tFNAs could mitigate organ inflammatory damage in septic mice, wherein they reduced inflammatory factor levels by inhibiting pyroptosis. These results provide possible new strategies for the future treatment of sepsis.

A dynamic DNA tetrahedron framework for active targeting.

An active targeting strategy-enabled DNA tetrahedron delivery vehicle could facilitate stable drug encapsulation and stimuli-responsive on-demand release, building a universal platform for different drug delivery requirements. Owing to the excellent biocompatible nature, programmability and remarkable cell and tissue permeability, the tetrahedral DNA nanostructure (TDN) has proven its value in the delivery of various bioactive molecules. We previously described this as a static multifunctional complex in our earlier protocol. However, static structures and passive targeting behavior might introduce off-target effects under complicated biological conditions. Therefore, in this Protocol Extension, we present a major update of the TDN delivery vehicle enabling an active targeting strategy to be used for stimuli-sensitive conformation changes and on-site cargo release, which could avoid drawbacks, including complex and time-consuming fabrication processes and undetermined cell penetration ability of other DNA-based delivery vehicles. Upon exquisite design of TDN size based on cargo type, one-pot annealing is applied to fabricate the Tiamat-designed TDN exoskeleton. Then the design of the dynamic DNA apparatus can be based on the target and environmental stimuli, including DNA strand hybridization-based and pH-sensitive DNA apparatus, and careful titration of strand lengths and mismatches is achieved using polyacrylamide and agarose gel electrophoresis, or fluorophore modifications. Finally, cargo loading strategies are designed, including site and stand titration and cargo encapsulation verification. The dynamic structures show promising targetability and effectiveness in antitumor and anti-inflammatory treatment in vitro and in vivo. Assembly and characterization in the lab takes ~5 d, and the timing for the verification of biostability and biological applications depends on the uses.

Tetrahedral framework nucleic acids alleviate irradiation-induced salivary gland damage.

In this study, we investigated the role of tetrahedral framework nucleic acids (tFNAs) in irradiation-induced salivary gland damage in vitro and in vivo. Irradiation-damaged submandibular gland cells (SMGCs) were treated with different concentrations of tFNAs. Cell activity was measured by CCK-8 assay. Cell death was detected by Calcein-AM/PI double staining. Cell apoptosis was assessed by flow cytometry. The expression of apoptosis proteins and inflammatory cytokines were detected by western blot. Body weight, drinking volume, saliva flow rate and lag time was measured 8 weeks after irradiation. Micromorphological changes of submandibular gland were assessed by haematoxylin-eosin and masson staining. Cell proliferation, apoptosis and microvessel density of submandibular gland were evaluated by immunohistochemical staining. tFNAs could promote cell proliferation, inhibit cell apoptosis of irradiation-damaged SMGCs and reduce irradiation induced cell death. Mechanism studies revealed that tFNAs inhibited cell apoptosis through regulating the Bcl-2/Bax/Caspase-3 signalling pathway and inhibited the release of TNF-α, IL-1ß and IL-6 to reduce cell damage caused by inflammation. Animal experiments showed that tFNAs could alleviate irradiation-induced weight loss, increased water intake, decreased saliva production and prolonged salivation lag time and could ameliorate salivary gland damage. tFNAs have a positive effect on alleviating irradiation-induced salivary gland damage and might be a promising agent for the treatment of this disease.