Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets.

BACKGROUND: The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. METHODS: The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium. RESULTS: JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. CONCLUSIONS: The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.

Insights into the carbonization mechanism of PAN-derived carbon precursor fibers and establishment of a kinetics-driven accelerated reaction template for atomistic simulation.

To better understand the chemistry behind the carbonization process of the polyacrylonitrile (PAN)-based precursor fibers and provide a more authentic virtual counterpart of the process-inherited model for process optimization and rational performance design, we develop arrow-pushing reaction routes for primary exhaust gas product (H2O/H2/HCN/N2/tar vapor) formation and a pragmatic kinetics-driven accelerated reaction template for atomistic simulation of the carbonization process overcoming traditional challenges in time scale discrepancy of the reaction-diffusion system. The results of enthalpy barriers from hybrid first principles calculations validate the rationality and sequence of conjectured reactions during the two-stage carbonization process. Conversion rates of the rate-determining steps under 300 s carbonization are also estimated based on Eyring's transition state theory realizing kinetics equivalency of the reaction extent. Process-control measurements are further demonstrated corresponding to the proposed mechanism. The iterative densified crosslinking scheme specially designed for the surface layer is implanted into the topological reaction molecular dynamics template and a series of highly devisable structural models during the whole evolutionary process from the pre-oxidized fiber to the pristine carbon fiber surface are successfully predicted. The ultimate structure of the model presents excellent similarity in carbon yield and elemental composition with the type II high strength carbon fiber surface.

Surrogate optimization of a lattice foot orthotic.

BACKGROUND: Additive manufacturing enables to print patient-specific Foot Orthotics (FOs). In FOs featuring lattice structures, the variation of the cell's dimensions provides a locally variable stiffness to meet the therapeutic needs of each patient. In an optimization problem, however, using explicit Finite Element (FE) simulation of lattice FOs with converged 3D elements is computationally prohibitive. This paper presents a framework to efficiently optimize the cell's dimensions of a honeycomb lattice FO for flat foot condition. METHODS: We built a surrogate based on shell elements whose mechanical properties were computed by the numerical homogenization technique. The model was submitted to a static pressure distribution of a flat foot and it predicted the displacement field for a given set of geometrical parameters of the honeycomb FO. This FE simulation was considered as a black-box and a derivative-free optimization solver was employed. The cost function was defined based on the difference between the predicted displacement by the model against a therapeutic target displacement. RESULTS: Using the homogenized model as a surrogate significantly accelerated the stiffness optimization of the lattice FO. The homogenized model could predict the displacement field 78 times faster than the explicit model. When 2000 evaluations were required in an optimization problem, the computational time was reduced from 34 days to 10 hours using the homogenized model rather than explicit model. Moreover, in the homogenized model, there was no need to re-create and re-mesh the insole's geometry in each iteration of the optimization. It was only required to update the effective properties. CONCLUSION: The presented homogenized model can be used as a surrogate within an optimization framework to customize cell's dimensions of honeycomb lattice FO in a computationally efficient manner.

Computationally efficient model to predict the deformations of a cellular foot orthotic.

BACKGROUND: Foot orthotics (FOs) are frequently prescribed to provide comfortable walking for patients. Finite element (FE) simulation and 3D printing pave the way to analyse, optimize and fabricate functionally graded lattice FOs where the local stiffness can vary to meet the therapeutic needs of each individual patient. Explicit FE modelling of lattice FOs with converged 3D solid elements is computationally prohibitive. This paper presents a more computationally efficient FE model of cellular FOs. METHOD: The presented FE model features shell elements whose mechanical properties were computed from the numerical homogenization technique. To verify the results, the predictions of the homogenized models were compared to the explicit model's predictions when the FO was under a static pressure distribution of a foot. To validate the results, the predictions were also compared with experimental measurements when the FO was under a vertical displacement at the medial longitudinal arch. RESULTS: The verification procedure showed that the homogenized model was 46 times faster than the explicit model, while their relative difference was less than 8% to predict the local minimum of out-of-plane displacement. The validation procedure showed that both models predicted the same contact force with a relative difference of less than 1%. The predicted force-displacement curves were also within a 90% confidence interval of the experimental measurements having a relative difference smaller than 10%. In this case, using the homogenized model reduced the computational time from 22 h to 22 min. CONCLUSION: The presented homogenized model can be therefore employed to speed up the FE simulation to predict the deformations of the cellular FOs.

Syntheses, structures and catalytic properties of Evans-Showell-type polyoxometalate-based 3D metal-organic complexes constructed from the semi-rigid bis(pyridylformyl)piperazine ligand and transition metals.

Herein, two novel Evans-Showell-type polyoxometalate (POM)-based metal-organic complexes, namely, {[Cu(L)(H2O)3][Cu(L)0.5(H2O)][Cu(L)0.5(H2O)4][Co2Mo10H4O38]}·5H2O (1) and [(H2L)0.5]2{[Zn(L)0.5(H2O)4]2[Co2Mo10H4O38]}·2H2O (2) (L = N,N'-bis(3-pyridinecarboxamide)-piperazine), were hydrothermally synthesized using a semi-rigid bis-pyridyl-bis-amide ligand and structurally characterized via single-crystal X-ray diffraction, elemental analysis, IR spectroscopy, powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). The single-crystal X-ray diffraction analysis shows that complex 1 is a 3D Evans-Showell-type POM-based metal-organic network. In complex 1, the 1D infinite double chain structure constructed from {{Cu[Co2Mo10H4O38]}4-L} units and the µ4-bridging L ligand are linked by quadrate Cu2L2 loops to form a 2D layer, which is further connected by µ2-bridging L ligands, forming a 3D (2,3,4)-connected metal-organic framework. Complex 2 displays 3D supramolecular networks based on 1D {[Co2Mo10H4O38]-Zn-L}n infinite chains, which are constructed from Evans-Showell-type polyoxoanions and µ2-bridging 3-bpfp ligands (via ligation of pyridyl nitrogen atoms). The different coordination modes of the POM polyanions, bis(pyridylformyl)piperazine ligands and ratios play key roles in the construction of the title complexes. Significantly, the ligand L shows a µ4-bridging coordination mode in complex 1, which is observed for the first time in a POM system. Compounds 1 and 2 represent the first examples of metal-organic complexes based on Evans-Showell-type polyoxoanion and transition metal-bis-pyrazine-bis-amide coordination complexes. The fluorescence properties of the title complexes are reported herein. In addition, the title complexes act as heterogeneous Lewis acid catalysts for the oxidation of benzyl alcohol, and can also be recovered and reused without any significant loss in activity. Significantly, compound 1 with a 3D metal-organic framework showed higher catalytic performance with 99.4% conversion and 98.8% selectivity for benzoic acid at 10 h than compound 2 with 3D supramolecular networks.