In Situ Growth 3D GDY-NCNTs Nanocomposites for High-Performance Supercapacitors.

New binary carbon composites (GDY-NCNTs and GDY-CNTs) with a three-dimensional porous structure, which are synthesized by an in situ growth method, are adopted in this article. The GDY-NCNTs composites exhibit excellent specific capacitance performance (679 F g-1, 2 mV s-1, 139% increase compared to GDY-CNTs) and good cycling stability (with a capacity retention rate of up to 116% after 10000 cycles). The three-dimensional porous structure not only promotes ion transfer and increases the effective specific surface area to improve its specific capacitance performance but also adapts to the volume expansion and contraction during the charging and discharging process to improve its cycling stability. The presence of nitrogen doping in the carbon nanotubes of GDY-NCNTs increases the surface defects of the composites, provides more electrochemical points, and improves the surface wettability of the composites, further improving the electrochemical performance of the composites.

Tuning Hole Transport Properties and Perovskite Crystallization via Pyridine-Based Molecules for Quasi-2D Perovskite Solar Cells.

Quasi-2D perovskites show great potential as photovoltaic devices with superior stability, but the power conversion efficiency (PCE) is limited by poor carrier transport. Here, it is simultaneously affected the hole transport layer (HTL) and the perovskite layer by incorporating pyridine-based materials into poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) to address the key problem above in 2D perovskites. With this approach, the enhanced optoelectronic performance of the novel PEDOT:PSS is due to electron transfer between the additives and PEDOT or PSS, as well as a dissociation between PEDOT and PSS based on experimental and theoretical studies, which facilitates the charge extraction and transfer. Concurrently, in-situ X-ray scattering studies reveal that the introduction of pyridine-based molecules alters the transformation process of the perovskite intermediate phase, which leads to a preferred orientation and ordered distribution caused by the Pb─N chemical bridge, achieving efficient charge transport. As a result, the pyridine-treated devices achieve an increased short-circuit current density (Jsc) and PCE of over 17%.

A Practical Tool for Risk-Based In-use Compatibility Assessments.

In drug development, in-use compatibility studies are crucial steps to ensure that the critical quality attributes of the drug product are maintained when in contact with administration components. But once the drug is in clinical trials, unanticipated variations in these components can stretch limited resources and lengthen timelines to market, as these changes must be assessed and approved to ensure continued patient safety. It's desirable to use a science-based risk evaluation to determine the extent of data and testing needed in these situations, but there is no standard for how such evaluations are done. We have developed an Excel™-based semi-quantitative risk assessment tool to determine whether in-use testing is needed when drug delivery sites or components are changed during a clinical trial. We developed the tool based on our multi-company experience with compatibility studies for many types of drug products targeted for various geographic regions. We have employed the tool as a means to expedite decision-making and, if appropriate, reduce testing in low-risk situations. The tool can save significant time and effort (our estimate is approximately at least 6-9 months off the development cycle) and can minimize pitfalls in clinical administration. While we have designed the tool for our drug products and for use with parenteral dosing regimens, the tool can be adapted for other situations as needed. It will be especially useful for companies with more limited resources.

Graphdiyne Oxide Quantum Dots: The Enhancement of Peroxidase-like Activity and Their Applications in Sensing H2O2 and Cysteine.

As one of the typical carbon nanomaterials, graphdiyne (GDY) with unique chemical, physical, and electronic properties has a great potential in various fields. Although it is an important member of carbon nanozymes, the research on its intrinsic enzyme mimetic properties and applications is still limited. Herein, graphdiyne oxide quantum dots (GDYO QDs) have been synthesized through oxidative cleavage, which exhibit enhanced peroxidase-like activity with lower Km and higher Vmax than those of most carbon-based nanozymes. The catalytic mechanism is explored, showing that the enhanced catalytic performance is attributed to the good conjugated structure, large number of oxygen-containing groups, and small-sized nanosheets with few layers. As a kind of peroxidase mimetic, the GDY-based nanozyme has excellent potential in sensing H2O2 and biological antioxidants through the colorimetric assay, with a linear range from 5 to 500 µM and detection limit of 1.5 µM for H2O2 and a linear range from 0 to 90 µM and detection limit of 0.48 µM for l-cysteine. Our work will be beneficial to develop high-performance artificial enzymes and to understand their mechanism for better applications.

High performance determination of Pb2+ in water by 2,4-dithiobiuret-Reduced graphene oxide composite with wide linear range and low detection limit.

In this work, a novel chelating adsorbent, 2, 4-dithiobiuret-reduced graphene oxide composite (DTB-RGO), was synthesized and worked as an electrochemical sensor for the determination of Pb2+. X-ray photoemission spectroscopy, Raman spectroscopy and Fourier transform-infrared spectroscopy were used to confirm the successful doping of the aminothiourea groups into the GO nanosheets through amide bond. The electrode modified with DTB-RGO shows two wide linear range 0.1-200 ng mL-1, 200-1000 ng mL-1 and relatively low detection limit 0.08 ng mL-1 for Pb2+, far below the level of 10 ng mL-1 proposed by WHO. This DTB-RGO modified electrode also presents satisfying selectivity, reproducibility, stability, and applicability for detection of Pb2+, providing a simple and promising platform to develop novel electrochemical sensor for detecting Pb2+ with higher performance.

Fluorescent activatable gadofullerene nanoprobes as NIR-MR dual-modal in vivo imaging contrast agent.

Dual mode imaging technology is widely developed to achieve the early-stage precision cancer diagnosis. Here we designed a dual-modal magnetic resonance/near infrared fluorescence optical imaging contrast agent (GdF-SS-NIR783) with the fluorescence activatable and safer gadofullerene. The nanoprobes were fabricated by conjugating the gadofullerene derivatives with a NIR fluorescence imaging agent (NIR783) via the disulfide bond. The obtained nanoprobes showed no fluorescence (OFF), but the fluorescence turned on when incubated within reduction environment such as GSH solution. The clear fluorescence signal in tumor site was observed obviously after their intratumor injection. The nanoprobes also revealed efficient MRI contrast enhancement both in vitro and in vivo. And they showed good biocompatibility and did not demonstrate any tissue toxicity in vivo. This work gave the new possibility in designing more efficient and safer nanoprobes for future medical diagnoses.

Gd@C82(OH)22 harnesses inflammatory regeneration for osteogenesis of mesenchymal stem cells through JNK/STAT3 signaling pathway.

Tissue injuries are inevitably accompanied with immune responses. Understanding the effects of biomaterials on immunology regulation is critical for biomaterial development and tissue regeneration. Inflammatory cytokines secreted from macrophages promote the migration of mesenchymal stem cells (MSCs) to the damaged tissue sites and their subsequent participation in tissue repair. However, the effects of inflammatory cytokines caused by tissue injury on MSC behaviors urgently need to be revealed. Understanding and subsequently manipulating the interactions between immune cells and stem cells will provide us with new therapeutic strategies for tissue regeneration. Nanoparticles having immunomodulatory properties can modulate MSCs' functions in the inflammatory microenvironment. In this study, an immunomodulatory nanoparticle Gd@C82(OH)22 was used to manipulate MSC differentiation in inflammatory microenvironment. The results suggested that macrophage-derived inflammation induces osteogenic differentiation of MSCs by activating the JNK/STAT3 pathway. Gd@C82(OH)22 modulates inflammation-induced differentiation of MSCs in a dose-dependent manner through the JNK/STAT3 pathway. Low concentration of Gd@C82(OH)22 facilitates osteogenesis and high concentration suppresses osteogenesis of hMSCs in the inflammatory microenvironment. This study suggests that Gd@C82(OH)22 can act as a promising immunomodulator to differentiate stem cells and improve stem cell-based therapeutic efficiency for biomedical regeneration in inflammatory microenvironments.

Study on the antigenicity of metallofullerenol: antibody production, characterization, and its enzyme immunoassay application.

With their intriguing structures and properties, metallofullerenols have attracted considerable attention in biological and medical applications. Due to the increasing biomedical interest, effective detection methods are important to monitor and control metallofullerenols. However, the detection of metallofullerenols becomes very difficult after polyhydroxylated modification due to the lack of detectable features. Antibody-based immunoassay methods have been important tools for detection and will better meet the needs of analysis of metallofullerenols. Thus, the antigenicity of metallofullerenol has been studied for the first time. In this study, no immune response was detected when metallofullerenol Gd@C82(OH)x was used as immunogen. However, the polyclonal antibody against metallofullerenol was produced using metallofullerenol-KLH (keyhole limpet hemocyanin) as immunogen, indicating that metallofullerenol can act as hapten. The specificity of the obtained antibody was investigated. It has been found that the hydroxyl groups on the surface of the carbon cage, the encapsulated metal, and the size and shape of the carbon cage did not affect the recognition specificity of the antibody. Based on the obtained antibody, an indirect competitive enzyme immunoassay was developed for the determination of metallofullerenol with detection limits of 18 ng/mL in PBS. This enzyme immunoassay method was successfully used to detect metallofullerenol in serum. This work can provide an innovative way to determine metallofullerenols. Graphical abstract The polyclonal antibody against metallofullerenol was produced using metallofullerenol-KLH (keyhole limpet hemocyanin) as immunogen. Based on the obtained antibody, a competitive enzyme immunoassay was developed for the determination of metallofullerenol.

Polyhydroxylated fullerenols regulate macrophage for cancer adoptive immunotherapy and greatly inhibit the tumor metastasis.

Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application. FROM THE CLINICAL EDITOR: The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.

Isomers of IC70BA and Their Photovoltaic Performance in Polymer Solar Cells.

Indene-C70 derivatives were synthesized, including indene-C70 mono-adduct (IC70MA), indene-C70 bis-adduct (IC70BA) and indene-C70 tris-adduct (IC70TA). All as-prepared fullerene adducts are in fact a mixture of isomers. The IC70BA mixture was further separated by high-performance liquid chromatography (HPLC) and two different IC70BA isomers were obtained. With the addition of the increased number of indene, the lowest unoccupied molecular orbital (LUMO) energy level of the C70 derivatives is also increased. IC70BA and its isomers have a slight difference in LUMO energy level, but show great differences in the absorption spectra. Polymer solar cells (PSCs) devices were fabricated under the same conditions with P3HT as donor, IC70BA and its isomer as acceptor, to examine the influence of the regioisomers on photovoltaic performance. The two IC70BA isomers exhibited varying power conversion efficiency (PCE) values of 2.80 and 3.18%, respectively, suggesting the molecular structure of the fullerene derivatives have an effect on polymer solar cells properties.

Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor.

The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82(OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82(OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82(OH)22 mediates these effects by blocking TGF-ß signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82(OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1α and TGF-ß activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a kind of non-toxic CSC specific inhibitors with significant therapeutic potential.

Synthesis and characterization of C70-corrole--a new electron transfer dyad.

A new electron transfer dyad, covalently linked C70-corrole, was prepared via C70 and 10-(4-Formylaryl)-5,15-bis(pentafluorophenyl). The structures and the properties of the new material were investigated by HPLC, MALDI-TOF-MS, UV-Vis-NIR spectroscopy, NMR, fluorescence analysis and CV/DPV. The free-energy of C70-corrole calculated by employing the redox potentials and singlet excited-state energy suggested the possibility of electron transfer from the excited singlet state of corrole to the fullerene entity, which agreed with the results of the theoretical calculation.

Polyhydroxylated metallofullerenols stimulate IL-1ß secretion of macrophage through TLRs/MyD88/NF-κB pathway and NLRP3 inflammasome activation.

Polyhydroxylated fullerenols especially gadolinium endohedral metallofullerenols (Gd@C82(OH)22) are shown as a promising agent for antitumor chemotherapeutics and good immunoregulatory effects with low toxicity. However, their underlying mechanism remains largely unclear. We found for the first time the persistent uptake and subcellular distribution of metallofullerenols in macrophages by taking advantages of synchrotron-based scanning transmission X-ray microscopy (STXM) with high spatial resolution of 30 nm. Gd@C82(OH)22 can significantly activate primary mouse macrophages to produce pro-inflammatory cytokines like IL-1ß. Small interfering RNA (siRNA) knockdown shows that NLRP3 inflammasomes, but not NLRC4, participate in fullerenol-induced IL-1ß production. Potassium efflux, activation of P2X7 receptor and intracellular reactive oxygen speciesare also important factors required for fullerenols-induced IL-1ß release. Stronger NF-κB signal triggered by Gd@C82(OH)22 is in agreement with higher pro-IL-1ß expression than C60(OH)22. Interestingly, TLR4/MyD88 pathway but not TLR2 mediates IL-1ß secretion in Gd@C82(OH)22 exposure confirmed by macrophages from MyD88(-/-)/TLR4(-/-)/TLR2(-/-) knockout mice, which is different from C60(OH)22. Our work demonstrated that fullerenols can greatly activate macrophage and promote IL-1ß production via both TLRs/MyD88/NF-κB pathway and NLRP3 inflammasome activation, while Gd@C82(OH)22 had stronger ability C60(OH)22 due to the different electron affinity on the surface of carbon cage induced by the encaged gadolinium ion.

Enhanced performance of inverted organic photovoltaic cells using CNTs-TiO(X) nanocomposites as electron injection layer.

In this study, we fabricated inverted organic photovoltaic cells with the structure ITO/carbon nanotubes (CNTs)-TiO(X)/P3HT:PCBM/MoO3/Al by spin casting CNTs-TiO(X) nanocomposite (CNTs-TiO(X)) as the electron injection layer onto ITO/glass substrates. The power conversion efficiency (PCE) of the 0.1 wt% single-walled nanotubes (SWNTs)-TiO(X) nanocomposite device was almost doubled compared with the TiO(X) device, but with increasing concentration of the incorporated SWNTs in the TiO(X) film, the performance of the devices appeared to decrease rapidly. Devices with multi-walled NTs in the TiO(X) film have a similar trend. This phenomenon mainly depends on the inherent physical and chemical characteristics of CNTs such as their high surface area, their electron-accepting properties and their excellent carrier mobility. However, with increasing concentration of CNTs, CNTs-TiO(X) current leakage pathways emerged and also a recombination of charges at the interfaces. In addition, there was a significant discovery. The incorporated CNTs were highly conducive to enhancing the degree of crystallinity and the ordered arrangement of the P3HT in the active layers, due to the intermolecular π-π stacking interactions between CNTs and P3HT.

Synthesis and evaluation of Bingel-Hirsch multiadducts of paramagnetic gadofullerene as potential magnetic resonance imaging contrast agents.

Water-soluble malonate multiadducts of paramagnetic gadolinium endohedral metallofullerene, Gd@C82[C(COOH)2]6 and Gd@C82[C(COOH)2]8, were synthesized by Bingel-Hirsch reaction. Gd@C82 was firstly reacted with diethyl bromomalonate in the presence of alkali metal hydride to produce malonic ester multiadducted derivatives, Gd@C82[C(COOCH2CH3)2]x (x = 3-8), by Bingel reaction. They were isolated and purified to obtain Gd@C82[C(COOCH2CH3)2]6 and Gd@C82[C(COOCH2CH3)2]8 by silica-gel column chromatography with a gradient elution method, which were subsequently hydrolyzed to yield water-soluble Gd@C82[C(COOH)2]6 and Gd@C82[C(COOH)2]8 by Hirsch reaction. The structures of the derivatives were characterized by Fourier transform infrared spectrometry and matrix assisted laser desorption ionization time-of-flight mass spectrometry. The longitudinal relaxivities of Gd@C82[C(COOH)2]8 and Gd@C82[C(COOH)2]6, in buffer solution, were found to be 18.20 and 11.08 mM(-1) s(-1) at concentration range between 0.001-0.025 mM Gd, and to be 12.71 and 6.73 mM(-1) s(-1) between 0.050-0.200 mM Gd, respectively. The results showed that the measured relaxivities for malonate derivatives of Gd@C82 were dependent on the concentration of these solutions and the number of hydrophilic carboxyl groups appended on the surface of the Gd@C82 cage.

Synthesis and characterization of Gd@C82-PVK and C60-PVK--a kind of fullerene-grafted polymer.

Different fullerene-grafted poly(N-vinylcarbazole) was synthesized by free radical polymerization and the influence of the amount of initiator, the reaction time and the reaction temperature on the polymerization was studied. Metallofullerene-grafted polymer (Gd@C82-PVK) was firstly synthesized and characterized by GPC, UV-vis, FTIR, DSC, XPS. The results demonstrated that the fullerenes had chemically combined with PVK. Fluorescence spectra suggested that the grafted fullerenes had certain influence on the fluorescence properties of the polymer. This is due to the better electron-attractive ability of fullerenes, which contributed a lot to form the electron donor-acceptor systems in fullerene-grafted poly(N-vinylcarbazole). Potential applications of this kind of materials in optical and memory devices were expected.

Oxidative degradation studies of an oxazolidinone-derived antibacterial agent, RWJ416457, in aqueous solutions.

The rates of oxidative degradation of a new antibacterial drug, RWJ416457, in aqueous solutions were investigated over the pH-range of 2 to 10. Two oxidative degradates were identified and the influences of pH, buffer concentration, metal ions, metal chelating agents, and temperatures were studied. The pH, metal chelating agents, and metal ions significantly changed the product distribution in addition to the degradation rate. Oxidative degradation is believed to follow a hydrogen abstraction (HAT) pathway. One degradate was the major product under acidic conditions and its predominance is attributed to a resonance-stabilized intermediate. The importance of the resonance structure was diminished under neutral and basic conditions. The product distribution changed and two degradates were formed in equal amounts. The study results guided the formulation development to minimize oxidation.

Interaction between fullerenes and single-wall carbon nanotubes: the influence of fullerene size and electronic structure.

A series of fullerenes and endohedral metallofullerenes peapods have been synthesized by supercritical method in high filling rate. The interaction between SWNTs and various kinds of fullerenes (C60, C70, C78, C84) and metallofullerenes (Gd@C82, Er@C82, Ho@C82, Y@C82) has been further investigated. The slight blue shift of G-band in Raman spectra with respect to pristine SWNTs was attributed to the charge transfer from SWNTs to fullerenes cage. The obvious RBM shift strongly depended on the distance between the inner wall of the SWNTs and the fullerene cage and also partly associated with the electronic structure of the fullerene. These results indicated that the interaction between fullerenes and SWNTs, which was considered to be the van de walls interaction, can be influenced by the cage size and the kind of fullerenes.

Structural change of metallofullerene: an easier thermal decomposition.

We have studied for the first time the structural change of high-purity metallofullerene (Gd@C(82)) upon heat treatment in an ultra-high vacuum system (10(-10) Torr) and examined the decomposition product through successive analysis with MS, IR, Raman, TEM, EDS and XPS. It was found that metallofullerene (Gd@C(82)) had fully collapsed at 580 °C which was lower than that for the complete destruction of C(60). The easier decomposition should be ascribed to the encapsulated metal in the carbon cage which could induce the deformation of the C-C bond. The analysis indicated that the broken metallofullerene (Gd@C(82)) became a kind of graphite-like material with a lot of defects. The Gd atoms leaked out from the carbon cage and aggregated together to form a regular arrangement.

Supercritical synthesis and characterization of SWNT-based one dimensional nanomaterials.

The present study developed a novel, fast and efficient method to synthesize one dimensional nanotube-based materials via supercritical reactions and supercritical fluids. It was proved that supercritical organic fluids were good media to take materials into the nanocavity, not only as solvents but also as reaction agents. Different kinds of metals (Ni, Cu, Ag) and fullerenes (C(60), C(70), C(78), C(84), Gd@C(82), Er@C(82), Ho@C(82), Y@C(82)) were successfully inserted into nanotubes with small diameters by this technique, with various supercritical fluids such as C(2)H(5)OH, CH(3)OH or C(6)H(5)CH(3). The filling rates were proved to be more than 90%. The high filling efficiency and the properties of the as-generated materials were characterized by TEM, Raman, EDS and XPS. In principle, this technique can be applied to construct new types of nanomaterials, if we choose the appropriate supercritical reaction and fluid in the CNTs.