Greenurquhart3437

BACKGROUND Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor. PATIENTS AND METHODS CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and 4 dosing schedules, 2 weekly [2 days on/5 days off; 3 days on/4 days off], 1 biweekly [3 days on/11 days off], and 1 monthly [4 days on/24 days off]). Primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early anti-tumor activity, pharmacokinetics, and pharmacodynamics. RESULTS This study enrolled 69 patients, 67 with solid tumors and 2 with diffuse large B-cell lymphoma (DLBCL). Median age was 57 years (range, 21-80) and median number of prior regimens was 4 (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in >2 patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of October 8, 2019, 1 patient with grade 2 astrocytoma achieved a complete response, 1 patient with endometrial carcinoma had a partial response, and 6 patients had prolonged stable disease ≥11 months. CONCLUSIONS CC-90010 is well-tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors. HYPOTHESIS Both hydroxamate and dithiocarbamate groups exhibit a unique bonding characteristic toward rare earth ions. A hydroxamic acid surfactant containing a dithiocarbamate group should possess a specific affinity to hydrophobize bastnaesite [(Ce, La)CO3F] flotation. EXPERIMENTS N-[(3-hydroxyamino)-propoxy]-N-octyl dithiocarbamate (OAHD) was synthesized, and its flotation mechanism toward bastnaesite was investigated by in situ AFM, FTIR, XPS, micro-flotation and contact angle. FINDINGS In situ AFM clearly observed that OAHD aggregated on bastnaesite surface, which improved the contact angle and surface hydrophobicity of bastnaesite. FTIR spectra and XPS recommended that OAHD's dithiocarbamate and hydroxamate groups co-anchored on bastnaesite surface through strong chemisorption, which strengthened the bonding affinity of bastnaesite toward OAHD. UV spectra showed that both dithiocarbamate and hydroxamate groups exhibited weak affinity toward Ca2+ ions, which benefited OAHD's selective flotation separation of bastnaesite from calcite. The co-adsorption and special hydrophobic structure improved OAHD's flotation performance. As a result, OAHD returned higher flotation selectivity for bastnaesite than OHA (n-octyl hydroxamic acid) which chemisorbed on bastnaesite surface only through the hydroxamate group and used the heptyl as hydrophobic group. To balance the Pt utilization and the durability is the key issue for developing Pt-based oxygen reduction reaction (ORR) catalysts, and constructing ultrathin one-dimensional (1D) structure provides a practical solution. Here, a facile CO-assisted strategy has been proposed for synthesizing PtFe nanowires (NWs) with an ultrathin diameter of one-nanometer and high aspect ratio for the first time, which demonstrates great universality and can be extended to a ternary system. The NWs are found to grow following an oriented attachment mechanism facilitated by the preferential adsorption and reducibility of CO. Based on composition regulation, PtFe NWs and PtFeCo NWs exhibit superior catalytic performance, of which the electrochemical active surface areas are extremely high, achieving 1.5 folds of that of Pt/C catalyst. Benefiting from the synergistic effect endowed by alloying and the ultrathin anisotropic structure, PtFe NWs and PtFeCo NWs show remarkable mass activity of 0.57 and 0.58 A mg-1Pt, respectively, and the durability also meet the 2020 standard of DOE, holding great application potential. In situ interfacial growth of nanoparticles induced by a Pickering emulsion is recognized as a practical method for the fabrication of hollow composites. Herein, hybrid hollow microspheres were prepared using cellulose nanocrystals (CNCs) emulsified water-dodecane system as a template. The hybrid microspheres were composed of zeolitic imidazolate framework-8 (ZIF-8) shells and CNCs surface-layers. ZIF-8 crystals formed and grew at the oil-water interface with a low ligand/metal ion molar ratio. The composite microspheres owned rich porous structure with a high surface area of 1240 m2 g-1 and performed obvious hydrophilicity owing to the role of CNCs layers. The two characters offered CNCs/ZIF-8 composite materials with very prominent adsorption capacity towards dyes (1060.2 mg g-1 for malachite green). Carbonization of CNCs/ZIF-8 composite materials afford ZIF-8 based materials more effective removal of methylene blue from water under sunlight, owing to the photocatalytic role of ZnO remained in carbonized product. This research paves the way to realize a variety of hollow CNCs/ZIFs hybrid materials for different application purposes. CHIR-98014 The exploration of flexible supercapacitors with high energy density is a matter of considerable interest to meet the demand of wearable electronic devices. In this work, with carbon nanotubes (CNTs) grown on carbon cloth (CC) as flexible substrate, NiCoP nanoflake-surrounded CNT nanoarrays (NiCoP/CNT) and N-doped carbon coated CNT nanoarrays (CNT@N-C) were synthesized on CC and utilized as cathode and anode materials for constructing flexible all-solid-state hybrid supercapacitor. Both them exhibit excellent electrochemical performance. NiCoP/CNT/CC composites can deliver a specific capacitance of 261.4 mAh g-1, and CNT@N-C/CC exhibits a high capacitance of 256 F g-1 at the current density of 0.5 A g-1. The hybrid supercapacitor built from the two well designed electrodes can provide a specific capacitance of 123.3 mAh g-1 at current density 1 mA g-1 within a potential window of 0-1.5 V and retain almost 85% of its initial capacitance after 5000 cycles. Furthermore, the flexible devices show the maximum energy density of 138.