Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca 2+ and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi 4− generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.

A fast multipole boundary element method (FMBEM) in a subsonic uniform flow is presented. It is based on the boundary integral equation (BIE) in a subsonic uniform flow. The convected Green's function complicates its multipole expansion as well as the implementation of the computer code. Although the Lorentz transformation allows the Helmholtz equation in the uniform flow to be reduced to the standard Helmholtz equation, the deformation of the domain complicates the boundary conditions and may cause the elements' distortion. In this work, the analytical evaluations of singular integrals are achieved. Then a nonsingular BIE in a subsonic uniform flow is obtained and is incorporated in building FMBEM with the plane wave multipole expansion of Green's function directly. Details on the implementation of the algorithm are described. Numerical examples including a pulsating sphere radiation problem, a multibody scattering problem and an aircraft model are performed to validate the accuracy and efficiency of the proposed method. Results show that FMBEM solutions are in good agreement with analytical solutions. The difference between the analytical moments and numerical moments is also investigated carefully in the implementation of the fast multipole method. Dramatical improvements on solution efficiency are observed by comparing the developed algorithm with the CBEM.