There has been significant interest in developing cell membrane-coated nanoparticles due to their unique abilities of biomimicry and biointerfacing. As the technology progresses, it becomes clear that the application of these nanoparticles can be drastically broadened if additional functions beyond those derived from the natural cell membranes can be integrated. Herein, we summarize the most recent advances in the functionalization of cell membrane-coated nanoparticles. In particular, we focus on emerging methods, including (1) lipid insertion, (2) membrane hybridization, (3) metabolic engineering, and (4) genetic modification. These approaches contribute diverse functions in a nondisruptive fashion while preserving the natural function of the cell membranes. They also improve on the multifunctional and multitasking ability of cell membrane-coated nanoparticles, making them more adaptive to the complexity of biological systems. We hope that these approaches will serve as inspiration for more strategies and innovations to advance cell membrane coating technology.
Cellular senescence is a state of irreversible cell cycle arrest associated with ageing. Senescence of different cardiac cell types can direct the pathophysiology of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cardiac fibrosis. While age-related telomere shortening represents a major cause of replicative senescence, the senescent state can also be induced by oxidative stress, metabolic dysfunction, and epigenetic regulation, among other stressors. It is critical that we understand the molecular pathways that lead to cellular senescence and the consequences of cellular senescence in order to develop new therapeutic approaches to treat cardiovascular disease. In this review, we discuss molecular mechanisms of cellular senescence, explore how cellular senescence of different cardiac cell types (including cardiomyocytes, cardiac endothelial cells, cardiac fibroblasts, vascular smooth muscle cells, valve interstitial cells) can lead to cardiovascular disease, and highlight potential therapeutic approaches that target molecular mechanisms of cellular senescence to prevent or treat cardiovascular disease.
Effective antibacterial treatment at the infection site associated with high shear forces remains challenging, owing largely to the lack of durably adhesive and safe delivery platforms that can enable localized antibiotic accumulation against bacterial colonization. Inspired by delivery systems mimicking marine mussels for adhesion, herein, we developed a bioadhesive nanoparticle-hydrogel hybrid (NP-gel) to enhance localized antimicrobial drug delivery. Antibiotics were loaded into polymeric nanoparticles and then embedded into a 3D hydrogel network that confers adhesion to biological surfaces. The combination of two distinct delivery platforms, namely nanoparticles and hydrogel, allows the hydrogel network properties to be independently tailored for adhesion while maintaining controlled and prolonged antibiotic release profile from the nanoparticles. The bioadhesive NP-gel developed here showed superior adhesion and antibiotic retention under high shear stress on a bacterial film, a mammalian cell monolayer, and mouse skin tissue. Under a flow environment, the NP-gel inhibited the formation of an Escherichia coli bacterial film. When applied on mouse skin tissue for 7 consecutive days, the NP-gel did not generate any observable skin reaction or toxicity, implying its potential as a safe and effective local delivery platform against microbial infections.
The explosion of multinational activities in recent decades is rapidly transforming the global landscape of industrial production. But are the emerging clusters of multinational production the rule or the exception? What drives the offshore agglomeration of multinational firms in comparison to the agglomeration of domestic firms? Using a unique worldwide plant-level dataset that reports detailed location, ownership, and operation information for plants in over 100 countries, we construct a spatially continuous index of agglomeration and analyze the different patterns underlying the global economic geography of multinational and non-multinational firms. We present new stylized facts that suggest the offshore clusters of multinationals are not a simple reflection of domestic industrial clusters. Agglomeration economies including technology diffusion and capital-good market externality play a more important role in the offshore agglomeration of multinationals than the agglomeration of domestic firms. These findings remain robust when we explore the process of agglomeration.
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