The inflammatory dysfunction of microglia from excess amyloid-β peptide (Aβ) disposal is an overlooked but pathogenic event in Alzheimer's disease (AD). Here, we exploit a native high-density lipoprotein (HDL)-inspired nanoscavenger (pHDL/Cur-siBACE1) that combines the trinity of phosphatidic acid-functionalized HDL (pHDL), curcumin (Cur), and β-site APP cleavage enzyme 1 targeted siRNA (siBACE1) to modulate microglial dysfunction. By mimicking the natural lipoprotein transport route, pHDL can penetrate the blood−brain barrier and sequentially target Aβ plaque, where Aβ catabolism is accelerated without microglial dysfunction. The benefit results are from a three-pronged modulation strategy, including promoted Aβ clearance with an antibody-like Aβ binding affinity, normalized microglial dysfunction by blocking the NF-κB pathway, and reduced Aβ production by gene silence (44%). After treatment, the memory deficit and neuroinflammation of APPswe/PSEN 1dE9 mice are reversed. Collectively, this study highlights the doubleedged sword role of microglia and provides a promising tactic for modulating microglial dysfunction in AD treatment.

Multi-objective land allocation (MOLA) can be regarded as a spatial optimization problem that allocates appropriate use to certain land units subjecting to multiple objectives and constraints. This article develops an improved knowledge-informed non-dominated sorting genetic algorithm II (NSGA-II) for solving the MOLA problem by integrating the patch-based, edge growing/decreasing, neighborhood, and constraint steering rules. By applying both the classical and the knowledge-informed NSGA-II to a simulated planning area of 30 × 30 grid, we find that: when compared to the classical NSGA-II, the knowledge-informed NSGA-II consistently produces solutions much closer to the true Pareto front within shorter computation time without sacrificing the solution diversity; the knowledge-informed NSGA-II is more effective and more efficient in encouraging compact land allocation; the solutions produced by the knowledge-informed have less scattered/isolated land units and provide a good compromise between construction sprawl and conservation land protection. The better performance proves that knowledge-informed NSGA-II is a more reasonable and desirable approach in the planning context.

No abstract

Through retrospective analysis of the literature on the cell repair of spinal cord injury worldwide, it is found that the mechanism of cell transplantation repairing spinal cord injury is mainly to replace damaged neurons, protect host neurons, prevent apoptosis, promote axonal regeneration and synapse formation, promote myelination, and secrete trophic factors or growth factors to improve microenvironment. A variety of cells are used to repair spinal cord injury. Stem cells include multipotent stem cells, embryonic stem cells, and induced pluripotent stem cells. The multipotent stem cells are mainly various types of mesenchymal stem cells and neural stem cells. Non-stem cells include olfactory ensheathing cells and Schwann cells. Transplantation of inhibitory interneurons to alleviate neuropathic pain in patients is receiving widespread attention. Different types of cell transplantation have their own advantages and disadvantages, and multiple cell transplantation may be more helpful to the patient’s functional recovery. These cells have certain effects on the recovery of neurological function and the improvement of complications, but further exploration is needed in clinical application. The application of a variety of cell transplantation, gene technology, bioengineering and other technologies has made the prospect of cell transplantation more extensive. There is a need to find a safe and effective comprehensive treatment to maximize and restore the patient’s performance.