The study of biomechanics and finite element analysis on a novel plate for tibial plateau fractures via anterolateral supra-fibular-head approach

Abstract For Schatzker type II split-depressed tibial plateau fractures involving the fractures of anterolateral and posterolateral columns (APC), the optimal fixation scheme is controversial. The objectives of this study were: (1) to introduce a newly designed plate for treating APC fractures via biomechanical tests and finite element analysis (FEA), and (2) to compare it with two conventional fixation methods. APC fracture models were created and randomly assigned to three groups (Groups A-C). Group A was fixed with a 3.5-mm lateral locking plate, Group B was fixed with a 3.5-mm lateral locking plate and two 3.5-mm cannulated screws (hybrid fixation). Group C was fixed with the newly designed plate. It is an arched locking plate for fixing the lateral tibial plateau via the anterolateral supra-fibular-head approach. Each fracture model experienced a gradually increasing axial compressive load ranging from 250 to 750 N using a customized indenter. Biomechanical analysis demonstrated that the newly designed plate showed the minimum displacement among the three methods, followed by the hybrid fixation method. Conversely, the 3.5-mm lateral locking plate displayed the maximum displacement in APC fractures (p < 0.05). FEA results indicated that at 750 N, the maximum displacements for Groups A-C were measured as 3.06 mm, 2.74 mm, and 2.08 mm, respectively. Moreover, the maximum stresses recorded for the implant in Groups A-C at 750 N were 208.32 MPa, 299.59 MPa, and 143.26 MPa, while for the bone, they were 47.12 MPa, 74.36 MPa, and 40.01 MPa. The overall trends at 250 N and 500 N were consistent with those observed at 750 N. In conclusion, due to good biomechanical performance and FEA results, the newly designed plate represents a promising choice for managing APC fractures of the tibial plateau

Triptolide induces growth inhibition and apoptosis of human laryngocarcinoma cells by enhancing p53 activities and suppressing E6-mediated p53 degradation.

Triptolide, an active compound extracted from Chinese herb Leigongteng (Tripterygium wilfordii Hook F.), shows a broad-spectrum of anticancer activity through its cytotoxicity. However, the efficacy of triptolide on laryngocarcinoma rarely been evaluated, and the mechanism by which triptolide-induced cellular apoptosis is still not well understood. In this study, we found that triptolide significantly inhibited the laryngocarcinoma HEp-2 cells proliferation, migration and survivability. Triptolide induces HEp-2 cell cycle arrest at the G1 phase and apoptosis through intrinsic and extrinsic pathways since both caspase-8 and -9 are activated. Moreover, triptolide enhances p53 expression by increasing its stability via down-regulation of E6 and E6AP. Increased p53 transactivates down-stream target genes to initiate apoptosis. In addition, we found that short time treatment with triptolide induced DNA damage, which was consistent with the increase in p53. Furthermore, the cytotoxicity of triptolide is decreased by p53 knockdown or use of caspases inhibitor. In conclusion, our results demonstrated that triptolide inhibits cell proliferation and induces apoptosis in laryngocarcinoma cells by enhancing p53 expression and activating p53 functions through induction of DNA damage and suppression of E6 mediated p53 degradation. These studies indicate that triptolide is a potential anti-laryngocarcinoma drug

Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice

Ibrutinib has potential therapeutic or protective effects against viral- and bacterial-induced acute lung injury (ALI), likely by modulating the Bruton tyrosine kinase (BTK) signaling pathway. However, ibrutinib has multi-target effects. Moreover, immunity and inflammation targets in ALI treatment are poorly defined. We investigated whether the BTK-, FLT3-, and EGFR-related signaling pathways mediated the protective effects of ibrutinib on ALI. The intratracheal administration of poly I:C or LPS after ibrutinib administration in mice was performed by gavage. The pathological conditions of the lungs were assessed by micro-CT and HE staining. The levels of neutrophils, lymphocytes, and related inflammatory factors in the lungs were evaluated by ELISA, flow cytometry, immunohistochemistry, and immunofluorescence. Finally, the expression of proteins associated with the BTK-, FLT3-, and EGFR-related signaling pathways were evaluated by Western blotting. Ibrutinib (10 mg/kg) protected against poly I:C-induced (5 mg/kg) and LPS-induced (5 mg/kg) lung inflammation. The wet/dry weight ratio (W/D) and total proteins in the bronchoalveolar lavage fluid (BALF) were markedly reduced after ibrutinib (10 mg/kg) treatment, relative to the poly I:C- and LPS-treated groups. The levels of ALI indicators (NF&kappa;B, IL-1&beta;, IL-6, TNF-&alpha;, IFN-&gamma;, neutrophils, and lymphocytes) were significantly reduced after treatment. Accordingly, ibrutinib inhibited the poly I:C- and LPS-induced BTK-, FLT3-, and EGFR-related pathway activations. Ibrutinib inhibited poly I:C- and LPS-induced acute lung injury, and this may be due to its ability to suppress the BTK-, FLT3-, and EGFR-related signaling pathways. Therefore, ibrutinib is a potential protective agent for regulating immunity and inflammation in poly I:C- and LPS-induced ALI

The stability of P2-layered sodium transition metal oxides in ambient atmospheres

Air-stability is a critical challenge faced by layered sodium transition metal oxide cathodes. Here, the authors depict a general and in-depth model of the structural/chemical evolution of P2-type layered oxides in air and propose an evaluation rule for the air-stability of layered sodium cathodes

Microfluidic-templated cell-laden microgels fabricated using phototriggered imine-crosslinking as injectable and adaptable granular gels for bone regeneration

Injectable granular gels consisting of densely packed microgels serving as scaffolding biomaterial have recently shown great potential for applications in tissue regeneration, which allow administration via minimally invasive surgery, on-target cargo delivery, and high efficiency in nutrient/waste exchange. However, limitations such as insufficient mechanical strength, structural integrity, and uncontrollable differentiation of the encapsulated cells in the scaffolds hamper their further applications in the biomedical field. Herein, we developed a new class of granular gels via bottom-up assembly of cell-laden microgels via photo-triggered imine-crosslinking (PIC) chemistry based on the microfluidic technique. The particulate nature of the granular gels rendered them with shear-thinning and self-healing behavior, thereby functioning as an injectable and adaptable cellularized scaffold for bone tissue regeneration. Specifically, single cell-laden, monodisperse microgels composed of methacrylate- and o-nitrobenzene-functionalized hyaluronic acid and gelatin were prepared using a high-throughput microfluidic technique with a production rate up to 3.7 × 108 microgels/hr, wherein the PIC chemistry alleviated the oxygen inhibition on free-radical polymerization and facilitated enhanced fabrication accuracy, accelerated gelation rate, and improved network strength. Further in vitro and in vivo studies demonstrated that the microgels can serve as carriers to support the activity of the encapsulated mesenchymal stem cells; these cell-laden microgels can also be used as cellularized bone fillers to induce the regeneration of bone tissues as evidenced by the in vivo experiment using the rat femoral condyle defect model. In general, these results represent a significant step toward the precise fabrication of engineered tissue mimics with single-cell resolution and high cell-density and can potentially offer a powerful tool for the design and applications of a next generation of tissue engineering strategy. Statement of significance: Using microfluidic droplet-based technology, we hereby developed a new class of injectable and moldable granular gels via bottom-up assembly of cell-laden microgels as a versatile platform for tissue regeneration. Phototriggered imine-crosslinking chemistry was introduced for microgel cross-linkage, which allowed for the fabrication of microgels with improved matrix homogeneity, accelerated gelation process, and enhanced mechanical strength. We demonstrated that the microgel building blocks within the granular gels facilitated the proliferation and differentiation of the encapsulated mesenchymal stem cells, which can further serve as a cellularized scaffold for the treatment of bone defects

Biological Characterizations of H5Nx Avian Influenza Viruses Embodying Different Neuraminidases

The H5 subtype virus of Highly Pathogenic Avian Influenza Virus has caused huge economic losses to the poultry industry and is a threat to human health. Until 2010, H5N1 subtype virus was the major genotype in China. Since 2011, reassortant H5N2, H5N6, and H5N8 viruses were identified in domestic poultry in China. The clade 2.3.4.4 H5N6 and H5N8 AIV has now spread to most of China. Clade 2.3.4.4 H5N6 virus has caused 17 human deaths. However, the prevalence, pathogenicity, and transmissibility of the distinct NA reassortment with H5 subtypes viruses (H5Nx) is unknown. We constructed five clade 2.3.4.4 reassortant H5Nx viruses that shared the same HA and six internal gene segments. The NA gene segment was replaced with N1, N2, N6, ΔN6 (with an 11 amino acid deletion at the 58th to 68th of NA stalk region), and N8 strains, respectively. The reassortant viruses with distinct NAs of clade 2.3.4.4 H5 subtype had different degrees of fitness. All reassortant H5Nx viruses formed plaques on MDCK cell monolayers, but the ΔH5N6 grew more efficiently in mammalian and avian cells. The reassortant H5Nx viruses were more virulent in mice as compared to the H5N2 virus. The H5N6 and H5N8 reassortant viruses exhibited enhanced pathogenicity and transmissibility in chickens as compared to the H5N1 reassortant virus. We suggest that comprehensive surveillance work should be undertaken to monitor the H5Nx viruses

Schematic diagram of hypothetic mechanisms underlying triptolide induction of apoptosis in laryngocarcinoma cells.

<p>Triptolide causes DNA damage to induce p53 transcription. Meanwhile triptolide enhances p53 protein stability by suppression of the E6-mediated p53 ubiquitinylation-mediated degradation. Elevated p53 initiates cell apoptosis through death receptors pathways and mitochondrial pathway via activating transcription and non-transcriptional functions (see Discussion for detail). </p

Triptolide up-regulated p53 mRNA level and enhanced p53 protein stabilization in laryngocarcinoma cells.

<p>(A) Triptolide enhanced p53 mRNA level in HEp-2 cells. Cells were treated with indicated doses of triptolide for 24h, p53 mRNA levels were determined by qRT-PCR using the specific primers. (B) Triptolide showed weak influence on the p53 mRNA stability. Cells were treated with 25μg/ml actinomycin D (AD) with or without 50 nM triptolide for indicated times, p53 and β-actin mRNA levels were determined by qRT-PCR and relative p53 mRNA level were presented. (C) Triptolide stabilized p53 protein level in HEp-2 cells. Cells were treated with 50μg/ml cycloheximide (CHX) with or without 50 nM triptolide for indicated times, p53 and β-actin protein levels were determined by western blot. (D) Effect of triptolide on p53 ubiquitination. HEp-2 cells were treated with 50 nM triptolide for indicated times, cell lysates were immunoprecipitated with p53 antibody and immunoblotted with Ub antibody. p53 and β-actin protein level were also presented. (E) Triptolide reduced E6 and E6AP expression in laryngocarcinoma cell. (F) Effect of triptolide on the interaction of p53 with E6 and E6AP. Cells were treated with indicated doses of triptolide and immunoprecipitated with p53 antibody, E6 and E6AP were immune-blotted. (G) and (H) Triptolide reduced E6 and E6AP expression in Hela and TC-1 cells. </p

Triptolide enhanced the anti-tumor effect of radiation on laryngocarcinoma cells.

<p>(A) The combination use of triptolide with radiation showed more inhibitory effect on the HEp-2 cells viability. Cells were seeded into 96 well plates with a density of 5000 cells per well. After pro-treatment with 10nM triptolide for 5h, cells were treated with various doses of X-ray radiation. Cell viability was detected with CCK8 assay. (B) The combination use of triptolide with radiation showed more inhibitory effect on the HEp-2 cells survivability. After pro-treatment with 10nM triptolide for 5h and radiated with 4 Gy, cells were then trypsonsized and plated in 60 mm plates with a density of 1000 cells per plate. 2 to 3 weeks later, cells were fixed and stained, and the numbers of colonies were counted and the survival fractions were calculated. </p