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Background AMP-activated protein kinase (AMPK) is a therapeutic target against type II diabetes (T2D). Synthetic sesquiterpene derivatives were investigated to identify novel AMPK activators as anti-diabetic drugs because the leading drugs like metformin and thiazolidinediones (TZDs) activate AMPK by inhibiting the synthesis of adenosine 5'-triphosphate and thus are associated with some side effects. Results We identified WSF-CT-11 as an AMPK activator in HEK293T cells and found that WSF-CT-11 activates AMPK by the activation of transient receptor potential vanilloid type 1 (TRPV1), a Ca2+-permeable cation channel. The increased Ca2+ influx then activates phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/Akt), and Ca2+/calmodulin-dependent protein kinase II (CaMKII), which in turn phosphorylates TRPV1 and facilitates the formation of a TRPV1/Akt/CaMKII/AMPK complex. This complex might be important for the regulation of AMPK activity. In 3T3-L1 adipocytes, WSF-CT-11-induced AMPK activation has three anti-diabetic effects. It promotes the assembly of high-molecular-weight adiponectin, which has stronger insulin-sensitizing activity than other multimers. It improves translocation of the glucose transporter type 4, increases glucose uptake, and induces the inhibitory phosphorylation of peroxisome proliferator-activated receptor γ and thus suppresses adipogenesis. Conclusion WSF-CT-11 is a novel AMPK activator and potential drug against T2D without the side effects of metformin and TZDs.

Following the development of organic mechanoluminescence (ML) materials, molecular packing was proved as the key point to the emission process under an external force. In this text, with the introduction of spiro-(fluorene-9-9'-xanthene) (SFX) unit as the building block, the molecular packing of the resultant compound (BSFXA) was optimized with the interlaced mode, directly leading to the efficient ML effect. The key role of SFX with a spiro-structure can be further confirmed by the ML inactivity of reference compound BFA with the replacement of SFX unit by dimethyl fluorene (MeF), which provided a novel strategy to construct organic ML luminogens.

Polymeric nanocarriers have been extensively used in medicinal applications for drug delivery. However, intravenous nanocarriers circulating in the blood will be rapidly cleared from the mononuclear macrophage system. The surface physicochemical characterizations of nanocarriers are the primary factors to determine their fate in vivo, such as evading the reticuloendothelial system, exhibiting long blood circulation times, and accumulating in the targeted site. In this work, we develop a series of polyurethane micelles containing segments of an anionic tripeptide, hydrophilic mPEG, and disulfide bonds. It is found that the long hydrophilic mPEG can shield the micellar surface and have a synergistic effect with the negatively charged tripeptide to minimize macrophage phagocytosis. Meanwhile, the disulfide bond can rapidly respond to the intracellular reduction environment, leading to the acceleration of drug release and improvement of the therapeutic effect. Our results verify that these anionic polyurethane micelles hold great potential in the development of the stealth immune system and controllable intracellular drug transporters.

“Grafting to” polymeric nanostructures or surfaces is a simple and versatile approach to achieve functionalization. Herein, we describe the formation of mixed polymer-grafted nanoparticles through a supramolecular “grafting to” method that exploits multiple hydrogen-bonding interactions between the thymine (T)-containing cores of preformed micelles and the complementary nucleobase adenine (A) of added diblock copolymers. To demonstrate this new “grafting to” approach, mixed-corona polymeric nanoparticles with different sizes were prepared by the addition of a series of complementary diblock copolymers containing thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) to a preformed micelle with a different coronal forming block, poly(4-acryloylmorpholine) (PNAM). PNIPAM chains were distributed throughout the corona and facilitated a fast and fully reversible size change of the resulting mixed-corona micelles upon heating. Through the introduction of an environmentally sensitive fluorophore, the reversible changes in nanoparticle size and coronal composition could be easily probed. Furthermore, preparation of mixed-corona micelles also enabled ligands, such as d-mannose, to be concealed and displayed on the micelle surface. This supramolecular “grafting to” approach provides a straightforward route to fabricate highly functionalized mixed polymeric nanostructures or surfaces with potential applications in targeted diagnosis or therapy and responsive surfaces.

Sodium-ion batteries offer an attractive option for grid-level energy storage due to the high natural abundance of sodium and low material cost of sodium compounds. Phosphorus (P) is a promising anode material for sodium-ion batteries, with a theoretical capacity of 2596 mAh/g. The red phosphorus (RP) form has worse electronic conductivity and lower initial Coulombic efficiency than black phosphorus (BP), but high material cost and limited production capacity have slowed the development of BP anodes. To address these challenges, we have developed a simple and scalable method to synthesize layered BP/graphene composite (BP/rGO) by pressurization at room temperature. A carbon-black-free and binder-free BP/rGO anode prepared with this method achieved specific charge capacities of 1460.1, 1401.2, 1377.6, 1339.7, 1277.8, 1123.78, and 720.8 mAh/g in a rate capability test at charge and discharge current densities of 0.1, 0.5, 1, 5, 10, 20, and 40 A/g, respectively. In a cycling performance test, after 500 deep cycles, the capacity of BP/rGO anodes stabilized at 1250 and 640 mAh/g at 1 and 40 A/g, respectively, which marks a significant performance improvement for sodium-ion battery anodes.

The shells of various poly(dl-lactide)-b-poly(acrylic acid) (PDLLA-b-PAA) spherical micelles and poly(l-lactide)-b-poly(acrylic acid) (PLLA-b-PAA) cylindrical micelles were functionalized with mannose to yield glyco-nanoparticles (GNPs) with different shapes and dimensions. All of these GNPs were shown to have good biocompatibility (up to 1 mg/mL). Cellular uptake experiments using RAW 264.7 have shown that the spherical GNPs were internalized to a much greater extent than the cylindrical GNPs and such a phenomenon was attributed to their different endocytosis pathways. It was demonstrated that spherical GNPs were internalized based on clathrin- and caveolin-mediated endocytosis while cylindrical GNPs mainly depended on clathrin-mediated endocytosis. We also found that longer cylindrical GNPs (Ln × Wn = 215 × 47 nm) can induce an inflammatory response (specifically interleukin 6) more efficiently than shorter cylindrical GNPs (Ln × Wn = 99 × 50 nm) and spherical GNPs (Dn = 46 nm).