Tetrahedral Framework Nucleic Acids Deliver Antimicrobial Peptides with Improved Effects and Less Susceptibility to Bacterial Degradation.

Antimicrobial peptides (AMPs) have been an attractive alternative to traditional antibiotics. However, considerable efforts are needed to further enhance their antimicrobial effects and stability against bacterial degradation. Tetrahedral framework nucleic acids (tFNAs), a new class of three-dimensional nanostructures, have been utilized as a delivery vehicle. In this study, tFNAs were combined for the first time with an antimicrobial peptide GL13K, and the effects of the resultant complexes against Escherichia coli (sensitive to GL13K) and Porphyromonas gingivalis (capable of degrading GL13K) were investigated. tFNA-based delivery enhanced the effects of GL13K against E. coli. The tFNA vehicle both increased bacterial uptake and promoted membrane destabilization. Moreover, it enhanced the effects of GL13K against P. gingivalis by protecting the peptide against degradation in the protease-rich extracellular environment. Therefore, tFNA provides a delivery vehicle for AMPs targeting a broad range of disease.

TUCNet: A channel and spatial attention-based graph convolutional network for teeth upsampling and completion.

With the increasing popularity of the use of 3D scanning equipment in capturing oral cavity in dental health applications, the quality of 3D dental models has become vital in oral prosthodontics and orthodontics. However, the point cloud data obtained can often be sparse and thus missing information. To address this issue, we construct a high-resolution teeth point cloud completion method named TUCNet to fill up the sparse and incomplete oral point cloud collected and output a dense and complete teeth point cloud. First, we propose a Channel and Spatial Attentive EdgeConv (CSAE) module to fuse local and global contexts in the point feature extraction. Second, we propose a CSAE-based point cloud upsample (CPCU) module to gradually increase the number of points in the point clouds. TUCNet employs a tree-based approach to generate complete point clouds, where child points are derived through a splitting process from parent points following each CPCU. The CPCU learns the up-sampling pattern of each parent point by combining the attention mechanism and the point deconvolution operation. Skip connections are introduced between CPCUs to summarize the split mode of the previous layer of CPCUs, which is used to generate the split mode of the current CPCUs. We conduct numerous experiments on the teeth point cloud completion dataset and the PCN dataset. The experimental results show that our TUCNet not only achieves the state-of-the-art performance on the teeth dataset, but also achieves excellent performance on the PCN dataset.

Management of Patients with Cervicofacial Edema and Paresthesia during Perioperative Period of Transoral Endoscopic Thyroidectomy.

Objective: To analyze the clinical intervention effect of transoral endoscopic thyroidectomy on the neck and face during perioperative period. Method: From January 2019 to January 2020, 60 patients included in this study were randomly divided into observation group and control group according to the ratio of 1 : 1, with 30 cases in each group. Both groups underwent rapid surgical intervention during the perioperative period. The patients in the observation group received neck and face management. The degree of jaw swelling, the degree of facial microexpression completion, and the changes in jaw and neck sensation were compared between the two groups. Results: There was no significant difference in neck and face swelling, pain, facial microexpression, and feeling between the two groups before operation. Patients with facial I/II swelling degree in the observation group were significantly more than in the control group, and the patients with III swelling degree were less than in the control group. There was significant difference for facial swelling between the two groups in the three intervention periods after the operation, and the difference was statistically significant (P < 0.05). The scores of facial microexpression in the observation group were higher than those in the control group during the three postoperative intervention periods, with statistical significance (P < 0.05). There was no significant difference in the pain score of the first day after surgery between the two groups (P = 0.298). In the other two postoperative intervention periods, the pain score of the observation group was lower than that of the control group, with a statistically significant difference, and the difference was statistically significant (P < 0.05). The threshold of chin and neck sensory pressure in the two groups was statistically significant (P < 0.05) except that the "cheek in area 4" (P = 0.290). Conclusion: The results showed that these interventions, such as the elevation of bed after operation, 24-hour intermittent cryotherapy, ice cubes in mouth, and the "meter" functional training, have good clinical effects on the symptoms of facial swelling and abnormal sensation of neck and face. It can accelerate the speed of edema dissipation, improve the patients' postoperative comfort, and improve the satisfaction and quality of life of patients with the effect of surgery and beauty.

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis.

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.

Injectable Supramolecular Hydrogel for Locoregional Immune Checkpoint Blockade and Enhanced Cancer Chemo-Immunotherapy.

Immunotherapy has revolutionized the therapeutic modalities of cancer treatment but is severely limited by a low objective response rate and the risk of immune-related side effects. Herein, an injectable supramolecular hydrogel is developed for local delivery of the DPPA-1 peptide (a d-peptide antagonist with a high binding affinity to programmed cell death-ligand 1 (PD-L1)) and doxorubicin (DOX). On the one hand, DOX could kill tumor cells directly and also induce immunogenic cell death to provoke the antitumor immune response. On the other hand, the DPPA-1 peptide could locoregionally block the PD-1/PD-L1 pathway to potentiate T-cell-mediated immune responses and minimize side effects. Eventually, by local injection of this supramolecular hydrogel, the synergistic cancer therapeutic effect was evaluated, showing promise in improving the objective response rate of immunotherapy and minimizing its systemic side effects.

Tetrahedral Framework Nucleic Acid Promotes the Treatment of Bisphosphonate-Related Osteonecrosis of the Jaws by Promoting Angiogenesis and M2 Polarization.

Bisphosphonates are often used to treat osteoporosis, malignant bone metastases, and hypercalcemia. However, it can cause serious adverse reactions, bisphosphonate-related osteonecrosis of the jaw (BRONJ), which seriously affects the quality of life of patients. At present, the treatment of BRONJ is still difficult to reach an agreement, and there is no effective treatment. Therefore, it is very important to find effective treatments. Many studies have shown that the occurrence of BRONJ may be due to unbalanced bone turnover, anti-angiogenesis, bacterial infection, direct tissue toxicity, and abnormal immune function. The previous research results show that tetrahedral framework nucleic acids (tFNAs), a new type of nanomaterial, can promote various biological activities of cells, such as cell proliferation, migration, anti-inflammation and anti-oxidation, and angiogenesis. Therefore, we intend to explore the potential of tFNAs in the treatment of BRONJ through this study. The results show that tFNAs can promote the treatment of BRONJ by promoting angiogenesis and promoting M2 polarization in macrophages and inhibiting M1 polarization both in vitro and in vivo. These results provide a theoretical basis for the application of tFNAs in the treatment of BRONJ and also provide new ideas and methods for the treatment of other diseases based on ischemia and immune disorders.

Design, fabrication and applications of tetrahedral DNA nanostructure-based multifunctional complexes in drug delivery and biomedical treatment.

Although organic nanomaterials and inorganic nanoparticles possess inherent flexibility, facilitating functional modification, increased intracellular uptake and controllable drug release, their underlying cytotoxicity and lack of specificity still cause safety concerns. Owing to their merits, which include natural biocompatibility, structural stability, unsurpassed programmability, ease of internalization and editable functionality, tetrahedral DNA nanostructures show promising potential as an alternative vehicle for drug delivery and biomedical treatment. Here, we describe the design, fabrication, purification, characterization and potential biomedical applications of a self-assembling tetrahedral DNA nanostructure (TDN)-based multifunctional delivery system. First, relying on Watson-Crick base pairing, four single DNA strands form a simple and typical pyramid structure via one hybridization step. Then, the protocol details four different modification approaches, including replacing a short sequence of a single DNA strand by an antisense peptide nucleic acid, appending an aptamer to the vertex, direct incubation with small-molecular-weight drugs such as paclitaxel and wogonin and coating with protective agents such as cationic polymers. These modified TDN-based complexes promote the intracellular uptake and biostability of the delivered molecules, and show promise in the fields of targeted therapy, antibacterial and anticancer treatment and tissue regeneration. The entire duration of assembly and characterization depends on the cargo type and modification method, which takes from 2 h to 3 d.

Uptake and adverse effects of polyethylene terephthalate microplastics fibers on terrestrial snails (Achatina fulica) after soil exposure.

Recent studies have demonstrated the occurrence of microplastic fibers (MFs) in soil environments. To determine whether MFs are harmful for soil biota, we evaluated toxic effects on terrestrial snails (Achatina fulica) after 28 d exposure to polyethylene terephthalate MFs at concentrations of 0.01-0.71 g kg-1 (dry soil weight). Digestion kinetics experiments on 24 snails showed that MFs can be ingested and excreted within 48 h. We found the appearance of cracks and deterioration on the surface of MFs after depuration by the digestive system. Prolonged exposure to 40 snails showed that 0.14-0.71 g kg-1 MFs caused an average reduction of 24.7-34.9% food intake and 46.6-69.7% excretion. 0.71 g kg-1 MFs induced significant villi damage in the gastrointestinal walls of 40% snails, but did not influence the histology of the liver and kidney. Moreover, 0.71 g kg-1 MFs exposure reduced glutathione peroxidase (59.3 ±â€¯13.8%) and total antioxidant capacity (36.7 ±â€¯8.5%), but elevated malondialdehyde level (58.0 ±â€¯6.4%) in the liver, which indicates oxidative stress is involved in the toxic mechanism. Our results suggest that MFs have adverse impacts on the fitness of soil organisms, and highlight the ecological risks of microplastic pollution in terrestrial ecosystems.

Substrate stiffness regulated migration and invasion ability of adenoid cystic carcinoma cells via RhoA/ROCK pathway.

OBJECTIVES: Human salivary adenoid cystic carcinoma (SACC) is one of the most common malignant tumours of the salivary gland and has strong migratory and invasive ability, which often lead to poor prognosis and lower survival rate. Tumour tissue tends to stiffen during solid tumour progression. This study aimed to investigate the influence of various substrate stiffness on the migration and invasion of SACC. METHODS: Salivary adenoid cystic carcinoma cell line ACC2 cells were cultured on polydimethylsiloxane substrates (PDMS) with varying stiffness for investigating the effects of substrate stiffness on the activities of MMPs and TIMPs. The underlying mechanism was also explored. RESULTS: When ACC2 cells were cultured on various stiffness of PDMS, the expressions of matrix metalloproteinases 2 (MMP2), MMP9, MMP14, RhoA, Rac1, Rho-associated protein kinase 1 (ROCK1) and ROCK2 were up-regulated with increasing substrate stiffness, whereas that of tissue inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP2 and TIMP4 were down-regulated with increasing substrate stiffness. CONCLUSIONS: Our results showed that substrate stiffness regulated the activities of MMPs and TIMPs and then modulate migratory and invasive ability of ACC2 cells via RhoA/ROCK pathway. This work indicate that matrix stiffness played an important role in progression of SACC, which not only can help understand the strong invasive ability of SACC, but also suggested that therapeutically targeting matrix stiffness may help reduce migration and invasion of SACC and improve effective therapies.

Microplastic and mesoplastic pollution in farmland soils in suburbs of Shanghai, China.

Microplastics are emerging pollutants which have been extensively detected in water environments. However, little is known about microplastic pollution in soil environments. In this study, we investigated microplastics and mesoplastics in farmland soils from twenty vegetable fields around the suburbs of Shanghai. In each site, three duplicate soil samples were collected from shallow (0-3 cm) and deep soils (3-6 cm), respectively. Microplastics (sizes of 20 µm - 5 mm) and mesoplastics (5 mm - 2 cm) were detected using methods of density extraction, 30% H2O2 digestion and micro-fourier transform infrared spectroscopy. The abundance of microplastics was 78.00 ±â€¯12.91 and 62.50 ±â€¯12.97 items kg-1 in shallow and deep soils, respectively. While, mesoplastics were found with abundance of 6.75 ±â€¯1.51 and 3.25 ±â€¯1.04 items kg-1 in shallow and deep soils. Among these micro(meso)plastics, 48.79% and 59.81% were in size of <1 mm in shallow and deep soils. The main morphotypes of microplastics included fiber, fragment and film, mostly in color of black or transparent. Moreover, we found that topsoil contained higher concentrations and larger sizes of micro(meso)plastics than deep soil. In addition, the vast majority of micro(meso)plastics were polypropylene (50.51%) and polyethylene (43.43%). This study reveals occurrence and characteristics of microplastic pollution in typical farmland soils. It provides important data for subsequent research on microplatics in the terrestrial ecosystem.

Microplastic particles cause intestinal damage and other adverse effects in zebrafish Danio rerio and nematode Caenorhabditis elegans.

Microplastics have been frequently detected in aquatic environments, and there are increasing concerns about potential effects on biota. In this study, zebrafish Danio rerio and nematode Caenorhabditis elegans were used as model organisms for microplastic exposure in freshwater pelagic (i.e. water column) and benthic (i.e. sediment) environments. We investigated the toxic effects of five common types of microplastics: polyamides (PA), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) and polystyrene (PS) particles. Results showed no or low lethality in D. rerio after exposure for 10d at 0.001-10.0mgL-1 microplastics. The PA, PE, PP and/or PVC microplastics with ~70µm size caused intestinal damage including cracking of villi and splitting of enterocytes. Exposure to 5.0mgm-2 microplastics for 2d significantly inhibited survival rates, body length and reproduction of C. elegans. Moreover, exposure to microplastics reduced calcium levels but increased expression of the glutathione S-transferase 4 enzyme in the intestine, which indicates intestinal damage and oxidative stress are major effects of microplastic exposure. Among 0.1, 1.0 and 5.0µm sizes of fluorescently labeled PS, 1.0µm particles caused the highest lethality, the maximum accumulation, the lowest Ca2+ level in the intestine and the highest expression of glutathione S-transferase 4 in nematodes. Taken together, these findings suggest that intestinal damage is a key effect of microplastics; and that the toxicity of microplastics is closely dependent on their size, rather than their composition.