No abstract

Spindle assembly required during mitosis depends on microtubule polymerization. We demonstrate that the evolutionarily conserved low-complexity protein, BuGZ, undergoes phase transition or coacervation to promote assembly of both spindles and their associated components. BuGZ forms temperature-dependent liquid droplets alone or on microtubules in physiological buffers. Coacervation in vitro or in spindle and spindle matrix depends on hydrophobic residues in BuGZ. BuGZ coacervation and its binding to microtubules and tubulin are required to promote assembly of spindle and spindle matrix in Xenopus egg extract and in mammalian cells. Since several previously identified spindle-associated components also contain low complexity regions, we propose that coacervating proteins may be a hallmark of proteins that comprise a spindle matrix that functions to promote assembly of spindles by concentrating its building blocks.

We report a facile approach to using laponite (LAP) nanodisks as a platform for efficient delivery of doxorubicin (DOX) to cancer cells. In this study, DOX was encapsulated into the interlayer space of LAP through an ionic exchange process with an exceptionally high loading efficiency of 98.3 ± 0.77%. The successful DOX loading was extensively characterized via different methods. In vitro drug release study shows that the release of DOX from LAP/DOX nanodisks is pH-dependent, and DOX is released at a quicker rate at acidic pH condition (pH = 5.4) than at physiological pH condition. Importantly, cell viability assay results reveal that LAP/DOX nanodisks display a much higher therapeutic efficacy in inhibiting the growth of a model cancer cell line (human epithelial carcinoma cells, KB cells) than free DOX drug at the same DOX concentration. The enhanced antitumor efficacy is primarily due to the much more cellular uptake of the LAP/DOX nanodisks than that of free DOX, which has been confirmed by confocal laser scanning microscope and flow cytometry analysis. The high DOX payload and enhanced antitumor efficacy render LAP nanodisks as a robust carrier system for different biomedical applications.

The development of biomass-based energy storage devices is an emerging trend to reduce the ever-increasing consumption of non-renewable resources. Here, nitrogen-doped carbonized bacterial cellulose (CBC-N) nanofibers are obtained by one-step carbonization of polyaniline coated bacterial cellulose (BC) nanofibers, which not only display excellent capacitive performance as the supercapacitor electrode, but also act as 3D bio-template for further deposition of ultrathin nickel-cobalt layered double hydroxide (Ni-Co LDH) nanosheets. The as-obtained CBC-N@LDH composite electrodes exhibit significantly enhanced specific capacitance (1949.5 F g(-1) at a discharge current density of 1 A g(-1) , based on active materials), high capacitance retention of 54.7% even at a high discharge current density of 10 A g(-1) and excellent cycling stability of 74.4% retention after 5000 cycles. Furthermore, asymmetric supercapacitors (ASCs) are constructed using CBC-N@LDH composites as positive electrode materials and CBC-N nanofibers as negative electrode materials. By virtue of the intrinsic pseudocapacitive characteristics of CBC-N@LDH composites and 3D nitrogen-doped carbon nanofiber networks, the developed ASC exhibits high energy density of 36.3 Wh kg(-1) at the power density of 800.2 W kg(-1) . Therefore, this work presents a novel protocol for the large-scale production of biomass-derived high-performance electrode materials in practical supercapacitor applications.

We report a facile approach to encapsulating amoxicillin (AMX) within laponite (LAP)-doped poly(lactic-co-glycolic acid) (PLGA) nanofibers for biomedical applications. In this study, a synthetic clay material, LAP nanodisks, was first used to encapsulate AMX. Then, the AMX-loaded LAP nanodisks with an optimized AMX loading efficiency of 9.76 ± 0.57% were incorporated within PLGA nanofibers through electrospinning to form hybrid PLGA/LAP/AMX nanofibers. The loading of AMX within LAP nanodisks and the loading of LAP/AMX within PLGA nanofibers were characterized via different techniques. In vitro drug release profile, antimicrobial activity, and cytocompatibility of the formed hybrid PLGA/LAP/AMX nanofibers were also investigated. We show that the loading of AMX within LAP nanodisks does not lead to the change of LAP morphology and crystalline structure and the incorporation of LAP/AMX nanodisks does not significantly change the morphology of the PLGA nanofibers. Importantly, the loading of AMX within LAP-doped PLGA nanofibers enables a sustained release of AMX, much slower than that within a single carrier of LAP nanodisks or PLGA nanofibers. Further antimicrobial activity and cytocompatibility assays demonstrate that the antimicrobial activity of AMX toward the growth inhibition of a model bacterium of Staphylococcus aureus is not compromised after being loaded into the hybrid nanofibers, and the PLGA/LAP/AMX nanofibers display good cytocompatibility, similar to pure PLGA nanofibers. With the sustained release profile and the reserved drug activity, the organic/inorganic hybrid nanofiber-based drug delivery system may find various applications in tissue engineering and pharmaceutical science.

We report a facile and economic approach to fabricating catalytic active palladium (Pd) nanoparticle (NP)-immobilized electrospun polyethyleneimine (PEI)/polyvinyl alcohol (PVA) nanofibers for catalytic reduction of hexavalent chromium (Cr(VI)) to trivalent chromium (Cr(III)). In this study, PEI/PVA nanofibrous mats were first electrospun from homogeneous mixture solution of PEI and PVA, followed by cross-linking with glutaraldehyde vapor to render the fibers with good water stability. The nanofibrous mats were then alternatively soaked in potassium tetrachloropallidate (K2PdCl4) and sodium borohydride solution, and the PdCl4(2-) anions complexed with the free amine groups of PEI were able to be reduced to form zero-valent Pd NPs. The formed Pd NP-containing PEI/PVA nanofibers were characterized by different techniques. We show that the immobilization of Pd NPs does not significantly change the morphology of the PEI/PVA nanofibers; instead the mechanical durability of the fibers is significantly improved. The formed Pd NPs with a mean diameter of 2.6 nm are quite uniformly distributed within the fibers with a small portion of particles having a denser distribution at the outer surface of the fibers. The catalytic activity and reusability of the fabricated Pd NP-containing fibrous mats were evaluated by transformation of Cr(VI) to Cr(III) in aqueous solution in the presence of a reducing agent. Our results reveal that the Pd NP-containing nanofibrous mats display an excellent catalytic activity and reusability for the reduction of Cr(VI) to Cr(III). The facile approach to fabricating metal NP-immobilized polymer nanofibers with a high surface area to volume ratio, enhanced mechanical durability, and uniform NP distribution may be extended to prepare different NP-immobilized fibrous systems for various applications in catalysis, sensing, environmental sciences, and biomedicine.

Development of novel nanomaterial-based contrast agents for targeted computed tomography (CT) imaging of tumors still remains a great challenge. Here we describe a novel approach to fabricating lactobionic acid (LA)-modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 pre-modified with fluorescein isothiocyanate and poly(ethylene glycol)-linked LA were employed as templates to form Au nanoparticles. The remaining dendrimer terminal amines were subjected to an acetylation reaction to form LA-Au DENPs. The prepared LA-Au DENPs were characterized via different methods. Our results reveal that the multifunctional Au DENPs with a Au core size of 2.7 nm have good stability under different pH (5-8) and temperature (4-50 °C) conditions and in different aqueous media, and are noncytotoxic to normal cells but cytotoxic to the targeted hepatocarcinoma cells in the given concentration range. In vitro flow cytometry data show that the LA-Au DENPs can be specifically uptaken by a model hepatocarcinoma cell line overexpressing asialoglycoprotein receptors through an active receptor-mediated targeting pathway. Importantly, the LA-Au DENPs can be used as a highly effective nanoprobe for specific CT imaging of hepatocarcinoma cells in vitro and the xenoplanted tumor model in vivo. The developed LA-Au DENPs with X-ray attenuation property greater than clinically employed iodine-based CT contrast agents hold a great promise to be used as a nanoprobe for targeted CT imaging of human hepatocellular carcinoma.

Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore, a multiprotein complex assembled onto centromeric DNA of the chromosome. Here, we show that Homo sapiens (Hs) NUF2 is required for stable kinetochore localization of centromere-associated protein E (CENP-E) in HeLa cells. HsNUF2 specifies the kinetochore association of CENP-E by interacting with its C-terminal domain. The region of HsNUF2 binding to CENP-E was mapped to its C-terminal domain by glutathione S-transferase pulldown and yeast two-hybrid assays. Suppression of synthesis of HsNUF2 by small interfering RNA abrogated the localization of CENP-E to the kinetochore, demonstrating the requirement of HsNUF2 for CENP-E kinetochore localization. In addition, depletion of HsNUF2 caused aberrant chromosome segregation. These HsNUF2-suppressed cells displayed reduced tension at kinetochores of bi-orientated chromosomes. Double knockdown of CENP-E and HsNUF2 further abolished the tension at the kinetochores. Our results indicate that HsNUF2 and CENP-E are required for organization of stable microtubule-kinetochore attachment that is essential for faithful chromosome segregation in mitosis.