3D U-Net Neural Network Architecture-Assisted LDCT to Acquire Vertebral Morphology Parameters: A Vertebral Morphology Comprehensive Analysis in a Chinese Population.

To evaluate the feasibility of acquiring vertebral height from chest low-dose computed tomography (LDCT) images using an artificial intelligence (AI) system based on 3D U-Net vertebral segmentation technology and the correlation and features of vertebral morphology with sex and age of the Chinese population. Patients who underwent chest LDCT between September 2020 and April 2023 were enrolled. The Altman and Pearson's correlation analyses were used to compare the correlation and consistency between the AI software and manual measurement of vertebral height. The anterior height (Ha), middle height (Hm), posterior height (Hp), and vertebral height ratios (VHRs) (Ha/Hp and Hm/Hp) were measured from T1 to L2 using an AI system. The VHR is the ratio of Ha to Hp or the ratio of Hm to Hp of the vertebrae, which can reflect the shape of the anterior wedge and biconcave vertebrae. Changes in these parameters, particularly the VHR, were analysed at different vertebral levels in different age and sex groups. The results of the AI methods were highly consistent and correlated with manual measurements. The Pearson's correlation coefficients were 0.855, 0.919, and 0.846, respectively. The trend of VHRs showed troughs at T7 and T11 and a peak at T9; however, Hm/Hp showed slight fluctuations. Regarding the VHR, significant sex differences were found at L1 and L2 in all age bands. This innovative study focuses on vertebral morphology for opportunistic analysis in the mainland Chinese population and the distribution tendency of vertebral morphology with ageing using a chest LDCT aided by an AI system based on 3D U-Net vertebral segmentation technology. The AI system demonstrates the potential to automatically perform opportunistic vertebral morphology analyses using LDCT scans obtained during lung cancer screening. We advocate the use of age-, sex-, and vertebral level-specific criteria for the morphometric evaluation of vertebral osteoporotic fractures for a more accurate diagnosis of vertebral fractures and spinal pathologies.

Hyaluronic-Acid-Nanomedicine Hydrogel for Enhanced Treatment of Rheumatoid Arthritis by Mediating Macrophage-Synovial Fibroblast Cross-Talk.

The occurrence of rheumatoid arthritis (RA) is highly correlated with progressive and irreversible damage of articular cartilage and continuous inflammatory response. Here, inspired by the unique structure of synovial lipid-hyaluronic acid (HA) complex, we developed supramolecular HA-nanomedicine hydrogels for RA treatment by mediating macrophage-synovial fibroblast cross-talk through locally sustained release of celastrol (CEL). Molecular dynamics simulation confirmed that HA conjugated with hydrophobic segments could interspersed into the CEL-loaded [poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone] (PECT) nanoparticles to form the supramolecular nanomedicine hydrogel HA-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-un-decanone)/PECT@CEL (HP@CEL), enabling fast hydrogel formation after injection and providing a 3-dimensional environment similar with synovial region. More importantly, the controlled release of CEL from HP@CEL inhibited the macrophage polarization toward the proinflammatory M1 phenotype and further suppressed the proliferation of synovial fibroblasts by regulating the Toll-like receptor pathway. In collagen-induced arthritis model in mice, HP@CEL hydrogel treatment substantial attenuated clinical symptoms and bone erosion and improved the extracellular matrix deposition and bone regeneration in ankle joint. Altogether, such a bioinspired injectable polymer-nanomedicine hydrogel represents an effective and promising strategy for suppressing RA progression through augmenting the cross-talk of macrophages and synovial fibroblast for regulation of chronic inflammation.

Display of CCL21 on cancer cell membrane through genetic modification using a pH low insertion peptide.

CCL21, a secondary lymphoid tissue chemokine, plays an important role in generating an effective anti-tumor immune response. In this study, a genetically modified CCL21 was developed by inserting a pH low insertion peptide to establish a CCL21-rich microenvironment for tumors. The fusion tag thioredoxin (Trx) was designed and fused at the N-terminal of the recombinant protein to protect it from being irrevocably misfolded in microbial host cells. The prokaryotic expression vector pET32a-CCL21-pHLIP was constructed and successfully expressed in E. coli BL21 (DE3) with a soluble expression form and a molecular weight of ~35 kDa. The induction conditions were optimized to obtain an extremely high yield of 6.7 mg target protein from 31.1 mg total protein. The 6xHis tagged Trx-CCL21-pHLIP was purified using Ni-NTA resin, and it was confirmed using SDS-PAGE and Western blot analyses. Consequently, the Trx-CCL21-pHLIP protein was successfully displayed on the cancer cell surface in a weak acidic microenvironment and showed the same ability as CCL21 in recruiting CCR7-positive cells. Additionally, the CCL21 fusion protein with or without Trx tag showed similar functions. Therefore, the study implies the feasibility of directing a modular genetic method for the development of protein-based drugs.

3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization.

The vascularization of bone repair materials is one of the key issues that urgently need to be addressed in the process of bone repair. The changes in macrophage phenotype and function play an important role in the process of vascularization, and endowing bone repair materials with immune regulatory characteristics to enhance angiogenesis is undoubtedly a new strategy to improve the effectiveness of bone repair. In order to improve the effect of tricalcium phosphate (TCP) on vascularization and bone repair, we doped strontium ions (Sr) into TCP (SrTCP) and prepared porous 3D printed SrTCP scaffolds using 3D printing technology, and studied the scaffold mediated macrophage polarization and subsequent vascularization and bone regeneration. The results of the interaction between the scaffold and macrophages showed that the SrTCP scaffold can promote the polarization of macrophages from M1 to M2 and secrete high concentrations of VEGF and PDGF-bb cytokines, which shows excellent angiogenic potential. When human umbilical vein endothelial cells (HUVECs) were co-cultured with macrophage-conditioned medium of SrTCP scaffold, HUVECs exhibited excellent early angiogenesis-promoting effects in terms of scratch healing, angiogenic gene expression, and in vitro tube formation performance. The results of in vivo bone repair experiments showed that the SrTCP scaffold formed a vascular network with high density and quantity in the bone defect area, which could increase the rate of new bone formation and advance the period of bone formation, and finally achieved a better bone repair effect. We observed a cascade effect in which Sr-doped SrTCP scaffold regulate macrophage polarization to enhance angiogenesis and promote bone repair, which may provide a new strategy for the repair of clinical bone defects.

A comparative study of the removal of o-xylene from gas streams using mesoporous silicas and their silica supported sulfuric acids.

The three types of silica supported sulfuric acids (SSA), with the same sulfuric acid loading of 9.25 mmol g-1, were prepared by a wet impregnation method from silica gel (SG), SBA-15 and MCM-41. Characterization of the prepared SSA showed that two anchoring states coexisted for sulfuric acid supported on the surface of the silicas: A physiosorbed (P)-state sulfuric acid; and a chemically bonded (C)-state sulfuric acid. Dynamic adsorption results showed that each SSA had a significant removal capacity for o-xylene gas in the reactive temperature regions. The ranges of the reactive regions were 120-220 °C (SSA/SG), 120-230 °C (SSA/SBA-15) and 120-250 °C (SSA/MCM-41), and this could be attributed to the sulfonation reaction between o-xylene and the anchored sulfuric acid. SSA/MCM-41 showed the highest theoretical breakthrough adsorption capacity (QB, th, 526.71 mg g-1) compared with SSA/SBA-15 (363.54 mg g-1) and SSA/SG (239.15 mg g-1). QB, th was closely associated with the amount or proportion of the C-state sulfuric acid on the surface of each SSA. Optimum breakthrough time and QB, th was obtained by increasing the bed height and decreasing flow rate and inlet concentration. The SSA exhibited excellent recyclability and reuse performance over eight consecutive adsorption/desorption/regeneration cycles. The results suggested that the SSA, especially SSA/MCM-41, might have good potential in applications using adsorbents for the removal of BTEX pollutants.

Structural and Mechanical Properties of Ionic Di-block Copolymers via a Molecular Dynamics Approach.

Polymerized ionic copolymers have recently evolved as a new class of materials to overcome the limited range of mechanical properties of ionic homopolymers. In this paper, we investigate the structural and mechanical properties of charged ionic homopolymers and di-block copolymers, while using coarse-grained molecular dynamics simulation. Tensile and compressive deformation are applied to the homopolymers and copolymers in the glassy state. The effect of charge ratio and loading direction on the stress-strain behavior are studied. It is found that the electrostatic interactions among charged pairs play major roles, as evidenced by increased Young's modulus and yield strength with charge ratio. Increased charge ratio lead to enhanced stress contribution from both bonding and pairwise (Van der Waals + coulombic) interaction. The increase in the gyration of the radius is observed with increasing charge ratio in homopolymers, yet a reversed tendency is observed in copolymers. Introduced charge pairs leads to an increased randomness in the segmental orientation in copolymers.

Effects of counterion size and backbone rigidity on the dynamics of ionic polymer melts and glasses.

It is well-known that the nature and size of the counterions affect the ionic conductivity and glass transition temperature of ionic polymers in a significant manner. However, the microscopic origin of the underlying changes in the dynamics of chains and counterions is far from completely understood. Using coarse-grained molecular dynamics simulations of flexible and semi-flexible ionic polymers, we demonstrate that the glass transition temperature of ionic polymeric melts depends on the size of monovalent counterions in a non-monotonic manner. The glass transition temperature is found to be the highest for the smallest counterions and decreases with an increase in the counterion radii up to a point, after which the glass transition temperature increases with a further increase in the radii. This behavior is because the counterions have significant effects on the coupled dynamics of the charges on the chains and counterions. In particular, increase in the radii of the counterions leads to strongly coupled dynamics between the charges on the chains and the counterions. The static dielectric constant of the polymer melts also has a significant effect on the coupling and the glass transition temperature. The glass transition temperature is predicted to decrease with an increase in the dielectric constant. This, in turn, leads to an increase in the diffusion constant of the counterions at a given temperature. Backbone rigidity is shown to increase the glass transition temperature and decrease the coupling. Furthermore, faster counterion dynamics is predicted for the melts of semi-flexible chains in comparison with flexible chains at the same segmental relaxation time. As the semi-flexible chains tend to have a longer segmental relaxation time, semi-flexible polymers with high dielectric constants are predicted to have diffusion constants of counterions comparable with flexible polymers.