From inflammation to bone formation: the intricate role of neutrophils in skeletal muscle injury and traumatic heterotopic ossification.

Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-ß signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.

E3 ubiquitin ligase casitas B-lineage lymphoma-b modulates T-cell anergic resistance via phosphoinositide 3-kinase signaling in patients with immune thrombocytopenia.

BACKGROUND: The E3 ubiquitin ligase casitas B-lineage lymphoma-b (CBLB) is a newly identified component of the ubiquitin-dependent protein degradation system and is considered an important negative regulator of immune cells. CBLB is essential for establishing a threshold of T-cell activation and regulating peripheral T-cell tolerance through various mechanisms. However, the involvement of CBLB in the pathogenesis of immune thrombocytopenia (ITP) is unknown. OBJECTIVES: We aimed to investigate the expression and role of CBLB in CD4+ T cells obtained from patients with ITP through quantitative proteomics analyses. METHODS: CD4+ T cells were transfected with adenoviral vectors overexpressing CBLB to clarify the effect of CBLB on anergic induction of T cells in patients with ITP. DNA methylation levels of the CBLB promoter and 5' untranslated region (UTR) in patient-derived CD4+ T cells were detected via MassARRAY EpiTYPER assay (Agena Bioscience). RESULTS: CD4+ T cells from patients with ITP showed resistance to anergic induction, highly activated phosphoinositide 3-kinase-protein kinase B (AKT) signaling, decreased CBLB expression, and 5' UTR hypermethylation of CBLB. CBLB overexpression in T cells effectively attenuated the elevated phosphorylated protein kinase B level and resistance to anergy. Low-dose decitabine treatment led to significantly elevated levels of CBLB expression in CD4+ T cells from 7 patients showing a partial or complete response. CONCLUSION: These results indicate that the 5' UTR hypermethylation of CBLB in CD4+ T cells induces resistance to T-cell anergy in ITP. Thus, the upregulation of CBLB expression by low-dose decitabine treatment may represent a potential therapeutic approach to ITP.

Shear models and parametric analysis of the PVC geomembrane-cushion interface in a high rock-fill dam.

As a type of flexible impermeable material, a PVC geomembrane must be cooperatively used with cushion materials. The contact interface between a PVC geomembrane and cushion easily loses stability. In this present paper, we analyzed the shear models and parameters of the interface to study the stability. Two different cushion materials were used: the common extrusion sidewall and non-fines concrete. To simulate real working conditions, flexible silicone cushions were added under the loading plates to simulate hydraulic pressure loading, and the loading effect of flexible silicone cushions was demonstrated by measuring the actual contact areas under different normal pressures between the geomembrane and cushion using the thin-film pressure sensor. According to elastomer shear stress, there are two main types of shear stress between the PVC geomembrane and the cushion: viscous shear stress and hysteresis shear stress. The viscous shear stress between the geomembrane and the cement grout was measured using a dry, smooth concrete sample, then the precise formula parameters of the viscous shear stress and viscous friction coefficient were obtained. The hysteresis shear stress between the geomembrane and the cushion was calculated by subtracting the viscous shear stress from the total shear stress. The formula parameters of the hysteresis shear stress and hysteresis friction coefficient were calculated. The three-dimensional box-counting dimensions of the cushion surface were calculated, and the formula parameters of the hysteresis friction were positively correlated with the three-dimensional box dimensions.

Horizontal seepage failure model and experimental study of damaged sidewalls of seams between geotube dam tubes.

The impact of damaged sidewalls at the joints between tubes on dam structures subjected to horizontal seepage is investigated. First, an experimental scheme is designed to test the mode and critical gradient of seepage failure of the soil in the damaged tubes. The effects of various overburden pressures (0, 5, 10, 20, and 30 kPa), hole radii(0.5, 1.0, 1.5, and 2 cm) and soil specimen properties were studied. The test phenomena and the changes in the pore water pressure were used to determine the seepage failure modes and the critical gradients under different conditions. Combined with the modified Terzaghi soil arching theory, a mathematical model was developed for the critical gradient for soil seepage failure. The model fitting curve was in good agreement with the laboratory test results. The critical gradient is independent of the overburden pressure and weakly dependent on the internal friction angle of the soil. The critical gradient increases with the cohesion. For fixed characteristic soil parameters, the critical gradient decreases at a gradually decreasing rate as the radius of the damaged hole increases.

A Facile Synthesis of Nitrogen-Doped Highly Porous Carbon Nanoplatelets: Efficient Catalysts for Oxygen Electroreduction.

The oxygen reduction reaction (ORR) is of great importance for various renewable energy conversion technologies such as fuel cells and metal-air batteries. Heteroatom-doped carbon nanomaterials have proven to be robust metal-free electrocatalysts for ORR in the above-mentioned energy devices. Herein, we demonstrate the synthesis of novel highly porous N-doped carbon nanoplatelets (N-HPCNPs) derived from oatmeal (or a biological material) and we show the materials' high-efficiency as electrocatalyst for ORR. The obtained N-HPCNPs hybrid materials exhibit superior electrocatalytic activities towards ORR, besides excellent stability and good methanol tolerance in both basic and acidic electrolytes. The unique nanoarchitectures with rich micropores and mesopores, as well as the high surface area-to-volume ratios, present in the materials significantly increase the density of accessible catalytically active sites in them and facilitate the transport of electrons and electrolyte within the materials. Consequently, the N-HPCNPs catalysts hold a great potential to serve as low-cost and highly efficient cathode materials in direct methanol fuel cells (DMFCs).