Mechanical nanosurgery of chemoresistant glioblastoma using magnetically controlled carbon nanotubes.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite multimodal treatment including surgery, radiotherapy, and chemotherapy, median patient survival has remained at ~15 months for decades. This situation demands an outside-the-box treatment approach. Using magnetic carbon nanotubes (mCNTs) and precision magnetic field control, we report a mechanical approach to treat chemoresistant GBM. We show that GBM cells internalize mCNTs, the mobilization of which by rotating magnetic field results in cell death. Spatiotemporally controlled mobilization of intratumorally delivered mCNTs suppresses GBM growth in vivo. Functionalization of mCNTs with anti-CD44 antibody, which recognizes GBM cell surface-enriched antigen CD44, increases mCNT recognition of cancer cells, prolongs mCNT enrichment within the tumor, and enhances therapeutic efficacy. Using mouse models of GBM with upfront or therapy-induced resistance to temozolomide, we show that mCNT treatment is effective in treating chemoresistant GBM. Together, we establish mCNT-based mechanical nanosurgery as a treatment option for GBM.

Alveolar bone height changes in the anterior tooth region before and after orthodontic treatment for Angle's Class II division 1 malocclusion and related factors.

BACKGROUND: The aim of this study was to observe the alveolar bone height changes in the anterior tooth region after orthodontic treatment for Angle's Class II division 1 malocclusion. METHODS: Ninety-three patients treated from January 2015 to December 2019 were retrospectively analyzed, of whom 48 received tooth extraction and 45 did not. RESULTS: After orthodontic treatment, the alveolar bone heights in the anterior tooth regions of tooth extraction and non-extraction groups decreased by 67.31% and 66.94%, respectively. Except for the maxillary and mandibular canines in the tooth extraction group as well as the labial side of maxillary anterior teeth and the palatal side of maxillary central incisors of the non-extraction group, the alveolar bone heights of other sites significantly reduced (P<0.05). The reduction in the alveolar bone height of the tooth extraction group significantly exceeded that of the non-extraction group on the palatal side of maxillary incisors and the lingual side of mandibular anterior teeth (P<0.05). CONCLUSIONS: Alveolar bone height in the anterior tooth region decreases after orthodontic treatment for Angle's Class II division 1 malocclusion, being closely related to tooth position together with movement direction and amplitude.

Microrobotic swarms for selective embolization.

Inspired by the collective intelligence in natural swarms, microrobotic agents have been controlled to form artificial swarms for targeted drug delivery, enhanced imaging, and hyperthermia. Different from these well-investigated tasks, this work aims to develop microrobotic swarms for embolization, which is a clinical technique used to block blood vessels for treating tumors, fistulas, and arteriovenous malformations. Magnetic particle swarms were formed for selective embolization to address the low selectivity of the present embolization technique that is prone to cause complications such as stroke and blindness. We established an analytical model that describes the relationships between fluid viscosity, flow rate, branching angle, magnetic field strength, and swarm integrity, based on which an actuation strategy was developed to maintain the swarm integrity inside a targeted region under fluidic flow conditions. Experiments in microfluidic channels, ex vivo tissues, and in vivo porcine kidneys validated the efficacy of the proposed strategy for selective embolization.

Human Periodontal Ligament Stem Cells Transplanted with Nanohydroxyapatite/Chitosan/Gelatin 3D Porous Scaffolds Promote Jaw Bone Regeneration in Swine.

Dental-tissue-derived stem cells have been used for tissue engineering owing to their ease of isolation and efficacy in in vitro and in vivo proliferation and differentiation. Nanohydroxyapatite/chitosan/gelatin (nHA/CG) three-dimensional porous scaffolds are promising for bone tissue engineering, especially jaw bone regeneration, because of their structural and functional similarity to natural bone. In our previous study, the efficiency of scaffolds with stem cell complexes in osteogenesis was confirmed in vivo in immunocompromised mice. However, studies on the bone regeneration efficiency of stem cell-seeded nHA/CG scaffolds using large animal jaw bone defect models have not been conducted. This study evaluated the bone regeneration potential of the nHA/CG scaffolds with transplanted human periodontal ligament stem cells (hPDLSCs) in critical-sized jaw bone defects in minipigs. The hPDLSCs isolated from periodontal ligaments of discarded teeth (postorthodontic purposes) were seeded onto the nHA/CG scaffolds. The scaffold was successfully synthesized according to our previous studies. Forty-eight critical-sized jaw bone defects were created in 12 minipigs. The defects were randomly assigned to one of three groups [scaffolds with seeded hPDLSCs (hPDLSCs/nHA/CG), only scaffold (nHA/CG), and a negative control group, ie, no cells and scaffolds implanted into defects] to investigate jaw bone regeneration. The bone regeneration capacities of the three groups were assessed for up to 12 weeks. The results showed that the hPDLSCs adhered well to the nHA/CG scaffold in vitro, and the cell-nHA/CG composites significantly increased new bone formation and generated large bones with normal architectures and vascularization in vivo compared to the nHA/CG and control groups. Immunohistochemistry staining showed that runt-related transcription factor 2 (Runx2) was highly expressed in the bone marrow formed in the hPDLSCs/nHA/CG group. This study provides strong evidence for future clinical applications of the nHA/CG scaffolds transplanted with hPDLSCs to regenerate the bone in large jaw bone defects.

Effect of the Histone Deacetylases Inhibitors on the Differentiation of Stem Cells in Bone Damage Repairing and Regeneration.

Tissue damage repairing and regeneration is a research hot topic. Tissue engineering arises at the historic moment which is a defect repair compound composed of seed cells, tissue engineering scaffolds, and inducing factors. Stem cells have a limited growth period in vitro culture, and they have a pattern of replicating ageing, and these disadvantages are limiting the applications of stem cells in basic research and clinical treatment. The enhancement of stem cell differentiation ability is a difficult problem to overcome, and it is possible to enhance the differentiation ability of stem cells through histone modification so as to provide a more robust foundation for damage repairing and regeneration. Studies have shown that Histone Deacetylases (HDAC) inhibitors can improve mesenchymal stem cells in vitro induced in different directions, conversion efficiency, increasing the feasibility and safety of stem cell therapy and tissue engineering, to offer reference to promote the stem cell therapy in clinical application. Therefore, this paper mainly focusing on the usage and achievements of the deacetylase inhibitors in stem cell differentiation studies and their use and prospects in repair of bone tissue defects.

Adjacent Y-Ion Ratio Distributions and Its Application in Peptide Sequencing.

A scoring function plays a critical role in software for peptide identification with mass spectrometry. We present a general scoring feature that can be incorporated in the scoring functions of other peptide identification software. The scoring feature is based on the intensity ratios between two adjacent y-ions in the spectrum. A method is proposed to obtain the probability distributions of such ratios, and to calculate the scoring feature based on the distributions. To demonstrate the performance of the method, the new feature is incorporated with X!Tandem [1] , [2] and Novor [3] and significantly improved the database search and de novo sequencing performances on the testing data, respectively.