PICALM is highly validated genetic risk factor for Alzheimer’s disease (AD). Here, we report that PICALM reductions in AD and murine brain endothelium correlate with amyloid–β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminishes Aβ clearance across the murine blood–brain barrier (BBB) and accelerates Aβ pathology that is reversible by endothelial PICALM re–expression. Using human brain endothelial monolayer, we show that PICALM regulates PICALM/clathrin–dependent internalization of Aβ bound to the low density lipoprotein receptor related protein–1, a key Aβ clearance receptor, and guides Aβ trafficking to Rab5 and Rab11 leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD–derived endothelial monolayers, which was reversible by adenoviral–mediated PICALM transfer. iPSC–derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance that has implications for Aβ brain homeostasis and clearance therapy.

Magnesium-based biodegradable metals (BMs) as bone implants have better mechanical properties than biodegradable polymers, yet their strength is roughly less than 350 MPa. In this work, binary Zn alloys with alloying elements Mg, Ca, Sr, Li, Mn, Fe, Cu, and Ag respectively, are screened systemically by in vitro and in vivo studies. Li exhibits the most effective strengthening role in Zn, followed by Mg. Alloying leads to accelerated degradation, but adequate mechanical integrity can be expected for Zn alloys when considering bone fracture healing. Adding elements Mg, Ca, Sr and Li into Zn can improve the cytocompatibility, osteogenesis, and osseointegration. Further optimization of the ternary Zn-Li alloy system results in Zn-0.8Li-0.4Mg alloy with the ultimate tensile strength 646.69 ± 12.79 MPa and Zn-0.8Li-0.8Mn alloy with elongation 103.27 ± 20%. In summary, biocompatible Znbased BMs with strength close to pure Ti are promising candidates in orthopedics for loadbearing applications.

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Zinc has been described as the "calcium of the twenty-first century." Zinc-based degradable biomaterials have recently emerged thanks to their intrinsic physiological relevance, biocompatibility, biodegradability, and pro-regeneration properties. Zinc-based biomaterials mainly include metallic zinc alloys, zinc ceramic nanomaterials, and zinc metal-organic frameworks (MOFs). Metallic zinc implants degrade at a desirable rate, matching the healing pace of local tissues, and stimulating remodeling and formation of new tissues. Zinc ceramic nanomaterials are also beneficial for tissue engineering and therapy thanks to their nanostructures and antibacterial properties. MOFs have large surface areas and are easily functionalized, making them ideal for drug delivery and cancer therapy. This review highlights recent developments in zinc-based biomaterials, discusses obstacles to overcome, and pinpoints directions for future research.

Excess hydrogen peroxide (H2O2) is produced in the pathogenesis of brain injuries and neurodegenerative diseases. H2O2 may damage cells through direct oxidation of lipids, proteins and DNA or it can act as a signaling molecule to trigger intracellular pathways leading to cell death. In this study, H2O2 caused plasma membranes of primary astrocytes to become more gel-like, while artificial membranes of vesicles composed of rat brain lipid extract became more liquid crystalline-like. Besides the effects on membrane phase properties, H2O2 promoted actin polymerization, induced the formation of cell-to-cell tunneling nanotube (TNT)-like connections among astrocytes and increased the colocalization of myosin Va with F-actin. Myosin Va was also observed in the H2O2-induced F-actin-enriched TNT-like connections. Western blot analysis suggests that H2O2 triggered the phosphorylation of the p38 mitogen-activated protein kinase (MAPK), and that SB203580, a specific inhibitor of p38 MAPK, suppressed the changes in membrane phase properties and cytoskeleton resulting from H2O2 treatment. These results suggest that H2O2 alters astrocyte membranes and the cytoskeleton through activation of the p38 MAPK pathway.

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Until now there has been no fundamental theory applicable for biodegradable metals (BMs). First, this paper optimizes the definition of BMs given in 2014. Second, the dual criteria of biodegradability and biocompatibility are proposed for BMs, and all metallic elements in the periodic table with accessible data are screened on the basis of these criteria. Regarding biodegradability, electrode potential, reactivity series, galvanic series, Pilling–Bedworth ratio, and Pourbaix diagrams are all adopted as parameters to classify the degradable and nondegradable nature of a material, especially in a physiological environment. Considering the biocompatibility at different levels, cellular biocompatibility, tissue biocompatibility, and human/clinical related biocompatibility parameters are put forward to comprehensively evaluate the biosafety of BMs. Third, for the material design of BMs, mechanical properties, chemical properties, physical properties and biological properties should be considered and balanced to guarantee that the degradation behavior of BMs match well with a tissue regeneration/repair procedure as the function of time and spatial location. Besides the selected metallic elements, some nonmetallic elements are selected as suitable alloying elements for BMs. Finally, five classification/research directions for future BMs are proposed: biodegradable pure metals, crystalline alloys, bulk metallic glasses, high entropy alloys, and metal matrix composites.

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