While electrochemical water splitting is one of the most promising methods to store light/electrical energy in chemical bonds, a key challenge remains in the realization of an efficient oxygen evolution reaction catalyst with large surface area, good electrical conductivity, high catalytic properties, and low fabrication cost. Here, a facile solution reduction method is demonstrated for mesoporous Co3O4 nanowires treated with NaBH4. The high‐surface‐area mesopore feature leads to efficient surface reduction in solution at room temperature, which allows for retention of the nanowire morphology and 1D charge transport behavior, while at the same time substantially increasing the oxygen vacancies on the nanowire surface. Compared to pristine Co3O4 nanowires, the reduced Co3O4 nanowires exhibit a much larger current of 13.1 mA cm‐2 at 1.65 V vs reversible hydrogen electrode (RHE) and a much lower onset potential of 1.52 V vs RHE. Electrochemical supercapacitors based on the reduced Co3O4 nanowires also show a much improved capacitance of 978 F g‐1 and reduced charge transfer resistance. Density‐functional theory calculations reveal that the existence of oxygen vacancies leads to the formation of new gap states in which the electrons previously associated with the Co‐O bonds tend to be delocalized, resulting in the much higher electrical conductivity and electrocatalytic activity.

Escherichia coli GlpG is an integral membrane protein that belongs to the widespread rhomboid protease family. Rhomboid proteases, like site-2 protease (S2P) and gamma-secretase, are unique in that they cleave the transmembrane domain of other membrane proteins. Here we describe the 2.1 A resolution crystal structure of the GlpG core domain. This structure contains six transmembrane segments. Residues previously shown to be involved in catalysis, including a Ser-His dyad, and several water molecules are found at the protein interior at a depth below the membrane surface. This putative active site is accessible by substrate through a large 'V-shaped' opening that faces laterally towards the lipid, but is blocked by a half-submerged loop structure. These observations indicate that, in intramembrane proteolysis, the scission of peptide bonds takes place within the hydrophobic environment of the membrane bilayer. The crystal structure also suggests a gating mechanism for GlpG that controls substrate access to its hydrophilic active site.

A FRET-based carbon nanodot (CDot) drug delivery platform has been developed. These CDots offer excellent biocompatibility, stable fluorescence, and efficient FRET between CDots and the attached fluorescent drug molecules, such as doxorubicin, enabling enhanced drug delivery, convenient cell imaging, and real-time monitoring of drug release. Moreover, the FRET-based two-photon imaging and drug tracking in deep tissues are also demonstrated.

FDA Commentary LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe indication and rationale for using azacitidine.2. Discuss the relative effectiveness of azacitidine. Identify the limitations of treatment with azacitidine.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME by guest on March 24, 2019 http://theoncologist.alphamedpress.org/ Downloaded fromThis material is protected by U.S. Copyright law.Unauthorized reproduction is prohibited. For reprints contact: Reprints@AlphaMedPress.com and 17 months respectively. Responding patients who were transfusion dependent at study entry lost the need for transfusions. In addition, about 19% of patients had less than partial responses (termed improvement), and two-thirds of them became transfusion independent. Common adverse events associated with azacitidine treatment were gastrointestinal (nausea, vomiting, diarrhea, constipation, and anorexia), hematologic (neutropenia, thrombocytopenia), fevers, rigors, ecchymoses, petechiae, injection site events, arthralgia, headache, and dizziness. Liver function abnormalities occurred in 16% of patients with intercurrent hepatobiliary disorders and in two patients with previously diagnosed liver cirrhosis. Renal failure occurred in patients during sepsis and hypotension. There were no deaths attributed to azacitidine. Azacitidine, the first drug approved by the U.S. FDA for MDS, has a favorable safety profile and provides a clinical benefit of eliminating transfusion dependence and complete or partial normalization of blood counts and bone marrow blast percentages in responding patients. The Oncologist 2005;10:176-182

The solar-driven water splitting process is highly attractive for alternative energy utilization, while developing efficient, earth-abundant, bifunctional catalysts for both oxygen evolution reaction and hydrogen evolution reaction has remained as a major challenge. Herein, we develop an ordered CoMnO@CN superlattice structure as an efficient bifunctional water-splitting electrocatalyst, in which uniform Co-Mn oxide (CoMnO) nanoparticles are coated with a thin, continuous nitrogen-doped carbon (CN) framework. The CoMnO nanoparticles enable optimized OER activity with effective electronic structure configuration, and the CN framework serves as an excellent HER catalyst. Importantly, the ordered superlattice structure is beneficial for enhanced reactive sites, efficient charge transfer, and structural stability. This bifunctional superlattice catalyst manifests optimized current densities and electrochemical stability in overall water splitting, outperforming most of the previously reported single- or bifunctional electrocatalysts. Combining with a silicon photovoltaic cell, this CoMnO@CN superlattice bifunctional catalyst enables unassisted solar water splitting continuously for ∼5 days with a solar-to-hydrogen conversion efficiency of ∼8.0%. Our discovery suggests that these transition metal oxide-based superlattices may serve as a unique structure modality for efficient bifunctional water splitting electrocatalysts with scale-up potentials.

The dose finding study of 54 patients showed a higher response rate for patients given 1.3 mg/m 2 compared with 1.0 mg/m 2 twice weekly for two of the 3-week schedule, but the study was too small for statistical dose-response comparisons. The most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness) in 65%, nausea (64%), diarrhea (51%), appetite decreased (including anorexia; 43%), constipation (43%), thrombocytopenia (43%), peripheral neuropathy (37%, including peripheral sensory neuropathy and peripheral neuropathy aggravated), pyrexia (36%), vomiting (36%), and anemia (32%).Conclusions: The FDA granted marketing approval to Millennium Pharmaceuticals on May 13, 2003 for bortezomib for use as a single agent for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Accelerated approval was based on a surrogate end point of response rate rather than clinical benefit, such as an improvement in survival. The recommended dose of bortezomib is 1.3 mg/m 2 administered twice weekly for 2 weeks (days 1, 4, 8, and 11) followed by a 10-day rest period (days 12-21). Accelerated approval was based on the results of two Phase II studies in a total of 256 patients and additional Phase I safety information. Mandated Phase IV study commitments to characterize clinical efficacy and safety more precisely are discussed.

Purpose:This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. Experimental Design: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. Results: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. Conclusions: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

We developed a postgrowth modification method of two-dimensional WO3 nanoflakes by a simultaneous solution etching and reducing process in a weakly acidic condition. The obtained dual etched and reduced WO3 nanoflakes have a much rougher surface, in which oxygen vacancies are created during the simultaneous etching/reducing process for optimized photoelectrochemical performance. The obtained photoanodes show an enhanced photocurrent density of ∼1.10 mA/cm(2) at 1.0 V vs Ag/AgCl (∼1.23 V vs reversible hydrogen electrode), compared to 0.62 mA/cm(2) of pristine WO3 nanoflakes. The electrochemical impedance spectroscopy measurement and the density functional theory calculation demonstrate that this improved performance of dual etched and reduced WO3 nanoflakes is attributed to the increase of charge carrier density as a result of the synergetic effect of etching and reducing.