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Context: Cushing disease (CD) is a life-threatening disorder. Therapeutic goals include symptom relief, biochemical control, and tumor growth inhibition. Current medical therapies for CD by and large exert no action on tumor growth.Objective: To identify drugs that inhibit corticotroph tumor adrenocorticotropic hormone (ACTH) secretion and growth.Design: High throughput screen employing a novel "gain of signal" ACTH AlphaLISA assay.Setting: Academic medical center.Patients: Corticotroph tumor tissues from patients with CD.Interventions: None.Main Outcome Measures: Potent inhibitors of corticotroph tumor ACTH secretion and growth.Results: From a kinase inhibitor library, we identified the dual PI3K/HDAC inhibitor CUDC-907 as a potent inhibitor of murine and human corticotroph tumor ACTH secretion (median effective concentration 1-5 nM), and cell proliferation (median inhibitory concentration 5 nM). In an in vivo murine corticotroph tumor xenograft model, orally administered CUDC-907 (300 mg/kg) reduced corticotroph tumor volume (TV [cm3], control 0.17 ± 0.05 vs CUDC-907 0.07 ± 0.02, P < .05) by 65% and suppressed plasma ACTH (ACTH [pg/mL] control 206 ± 27 vs CUDC-907 47 ± 7, P < .05) and corticosterone (corticosterone [ng/mL] control 180 ± 87 vs CUDC-907 27 ± 5, P < .05) levels by 77% and 85% respectively compared with controls. We also demonstrated that CUDC-907 acts through HDAC1/2 inhibition at the proopiomelanocortin transcriptional level combined with its PI3K-mediated inhibition of corticotroph cell viability to reduce ACTH secretion.Conclusions: Given its potent efficacy in in vitro and in vivo models of CD, combined with proven safety and tolerance in clinical trials, we propose CUDC-907 may be a promising therapy for CD. [ABSTRACT FROM AUTHOR]

Na3–2xMgxV2(PO4)3/C (0 ≤ x ≤ 0.2) were synthesized by a sol–gel method. According to X-ray diffraction (XRD) Rietveld refinement and energy dispersive spectroscopy (EDS) mapping results, Mg ions were approved to occupy the Na2 (18e) site in Na3–2xMgxV2(PO4)3/C for the first time. The amount of Mg substitution in Na3–2xMgxV2(PO4)3/C was optimized. The specific discharge capacities of Na2.9Mg0.05V2(PO4)3/C at 10 C, 20 C, and 30 C were 98.9%, 91.5%, and 76.2% of the value obtained at 1 C, respectively. Na2.9Mg0.05V2(PO4)3/C exhibited the highest capacity retention of 80.3% with a discharge capacity of 77.3 mAh·g−1 after 1200 cycles at 10 C. Na2.9Mg0.05V2(PO4)3/C exhibited superior rate performance, resulting from a high sodium diffusion coefficient (DNa) of 3.91 × 10–12 cm2·s−1 and the excellent electrical conductivity (5.7 × 10–2 s·cm−1). Combining the X-ray photoelectron spectroscopy (XPS) and Electrochemical impedance spectroscopy (EIS) results, the mechanism of Mg substitution was investigated. Since two Na+ were replaced by one Mg2+, V Na ′ was produced to maintain valence equilibrium. This phenomenon benefited Na+ migration by broadening the diffusion channel in the structure of Na3V2(PO4)3. According to the EPR results, the signal intensity of Na2.9Mg0.05V2(PO4)3/C was much stronger than that of Na3V2(PO4)2/C, thus confirming the existence of V Na ′ after Mg substitution. When the amount of Mg substitution was further increased to 0.1, the DNa decreased because of the small radius of Mg2+, which led to severe lattice distortion and volumetric shrinkage of the unit cell. [ABSTRACT FROM AUTHOR]

Boron-modified Li(Ni0.8Co0.1Mn0.1)1−xBxO2 cathode materials(NCM811) were successfully prepared by a nano-milling assisted solid-state approach. X-ray diffraction investigations showed that the materials are solid solutions with a layered structure. SEM observations implied that the doped B ions promoted the growth of the target crystal with well-developed facets since it will form liquid phase at lower temperature. The intensity ratio of I(003)/I(104) raised with the increase in Boron doping concentration, until a maximum value of 1.453 was observed at x = 0.01. Further Rietveld refinements revealed that boron ions occupy the crystal lattice in the transition metal slab which helps to promote the lattice ordering by decreasing the Li/Ni ionic mixing. Such B promoted NCM811 cathode materials were confirmed to have an improved diffusion coefficient with a reduced interfacial resistance by subsequent CV and EIS measurements. From the electrochemical test, those B modified NCM811 cathode materials presented enhanced electrochemical performance. Among the synthesized samples, Li(Ni0.8Co0.1Mn0.1)0.99B0.01O2 exhibited the best specific capacity, with 194.7 mAh g−1 and 166.8 mAh g−1 at 0.1C and 5C respectively. The capacity retention at 0.5C was also confirmed as 98.2% after 100 cycles. Such improvement can be explained by the reduced Li/Ni ionic mixing, the increased Li ionic diffusion and the reduced interfacial resistance caused by the promoted growth of the B doped NCM811 crystals. Compared to those NCM811 materials reported elsewhere, the material obtained by this approach showed high potential for future application. [ABSTRACT FROM AUTHOR]

Vat photopolymerization 3D printing of Si 3 N 4 ceramics has attracted great attention recently. To overcome the low curing depth limitation caused by α-Si 3 N 4 , β-Si 3 N 4 with low absorbance and large particle size was selected in this paper. After printing, the effects of pressureless sintering temperatures on mechanical and dielectric properties were systematically investigated. At 1800 °C, the real permittivity of Si 3 N 4 ceramics was 7.37, and the maximum bending strength was 367 ± 75 MPa. Considering the application of Si 3 N 4 ceramics in radomes/windows, the dielectric constant of Si 3 N 4 ceramics should be further reduced. Therefore, the octet-truss lattice structure was introduced to optimize the porosity of ceramics. As the porosity increased from 25% to 36%, the real permittivity decreased from 5.56 to 4.42, and the bending strength ranged from 98 ± 7–62 ± 13 MPa. It shows that vat photopolymerization 3D printing can be a promising technology for the fabrication of wave-transparent Si 3 N 4 ceramics. [ABSTRACT FROM AUTHOR]

A cost effective and eco-friendly approach for the preparation of LiFePO4/C cathode material is proposed in this paper. High-purity natural mineral magnetite (Fe3O4 ≥ 99%) was employed as the only ferric source in the synthesis routine. By ultrafine ball milling and subsequent oxidation, the magnetite was converted into FePO4·2H2O. After dehydration, the iron phosphate reacted with Li2CO3 and sucrose to form the target LiFePO4/C composite. Mössbauer result revealed that all the Fe cations exhibited + 2 valence state in the LiFePO4 lattice although redox process of the species occurred during the synthesis. SEM observations indicated that the pure phase LiFePO4 powders with round shape were constructed by fine primary grains with size of 100–200 nm. Such micro-nano structure offered an increased Li diffusion by increasing the surface area and reducing the migration pathway. LiFePO4/C composite synthesized by this magnetite approach exhibited excellent performance with a specific capacity of 161.1 mAh g−1 at 0.1 C and a capacity retention rate of 98.8% after 100 cycles at 1 C. The new approach we proposed presents the remarkable advantages of low cost and environmental friendliness, and therefore suggest significant potential in mass production. [ABSTRACT FROM AUTHOR]