Cancer nanotherapeutics are rapidly progressing and are being implemented to solve several limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. To improve the biodistribution of cancer drugs, nanoparticles have been designed for optimal size and surface characteristics to increase their circulation time in the bloodstream. They are also able to carry their loaded active drugs to cancer cells by selectively using the unique pathophysiology of tumors, such as their enhanced permeability and retention effect and the tumor microenvironment. In addition to this passive targeting mechanism, active targeting strategies using ligands or antibodies directed against selected tumor targets amplify the specificity of these therapeutic nanoparticles. Drug resistance, another obstacle that impedes the efficacy of both molecularly targeted and conventional chemotherapeutic agents, might also be overcome, or at least reduced, using nanoparticles. Nanoparticles have the ability to accumulate in cells without being recognized by P-glycoprotein, one of the main mediators of multidrug resistance, resulting in the increased intracellular concentration of drugs. Multifunctional and multiplex nanoparticles are now being actively investigated and are on the horizon as the next generation of nanoparticles, facilitating personalized and tailored cancer treatment.

A fractured microstructure design: A new type of piezoresistive sensor with ultra-high-pressure sensitivity (0.26 kPa(-1) ) in low pressure range (<2 kPa) and minimum detectable pressure of 9 Pa has been fabricated using a fractured microstructure design in a graphene-nanosheet-wrapped polyurethane (PU) sponge. This low-cost and easily scalable graphene-wrapped PU sponge pressure sensor has potential application in high-spatial-resolution, artificial skin without complex nanostructure design.

Highly stretchable graphene-nanocellulose composite nanopaper is fabricated for strain-sensor applications. Three-dimensional macroporous nanopaper from crumpled graphene and nanocellulose is embedded in elastomer matrix to achieve stretchability up to 100%. The stretchable graphene nanopaper is demonstrated for efficient human-motion detection applications.

The Warburg effect describes a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose even in the presence of oxygen. To better understand how tyrosine kinase signaling, which is commonly increased in tumors, regulates the Warburg effect, we performed phosphoproteomic studies. We found that oncogenic forms of fibroblast growth factor receptor type 1 inhibit the pyruvate kinase M2 (PKM2) isoform by direct phosphorylation of PKM2 tyrosine residue 105 (Y 105 ). This inhibits the formation of active, tetrameric PKM2 by disrupting binding of the PKM2 cofactor fructose-1,6-bisphosphate. Furthermore, we found that phosphorylation of PKM2 Y 105 is common in human cancers. The presence of a PKM2 mutant in which phenylalanine is substituted for Y 105 (Y105F) in cancer cells leads to decreased cell proliferation under hypoxic conditions, increased oxidative phosphorylation with reduced lactate production, and reduced tumor growth in xenografts in nude mice. Our findings suggest that tyrosine phosphorylation regulates PKM2 to provide a metabolic advantage to tumor cells, thereby promoting tumor growth.

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The Dobzhansky-Muller model proposes that hybrid incompatibilities are caused by the interaction between genes that have functionally diverged in the respective hybridizing species. Here, we show that Lethal hybrid rescue (Lhr) has functionally diverged in Drosophila simulans and interacts with Hybrid male rescue (Hmr), which has functionally diverged in D. melanogaster, to cause lethality in F1 hybrid males. LHR localizes to heterochromatic regions of the genome and has diverged extensively in sequence between these species in a manner consistent with positive selection. Rapidly evolving heterochromatic DNA sequences may be driving the evolution of this incompatibility gene.

Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod degeneration is accompanied by early infiltration of microglia, upregulation of phagocytic molecules in microglia, and presentation of “eat-me” signals on mutated rods. On live-cell imaging, infiltrating microglia interact dynamically with photoreceptors via motile processes and engage in rapid phagocytic engulfment of non-apoptotic rods. Microglial contribution to rod demise is evidenced by morphological and functional amelioration of photoreceptor degeneration following genetic ablation of retinal microglia. Molecular inhibition of microglial phagocytosis using the vitronectin receptor antagonist cRGD also improved morphological and functional parameters of degeneration. Our findings highlight primary microglial phagocytosis as a contributing mechanism underlying cell death in retinitis pigmentosa and implicate microglia as a potential cellular target for therapy.