Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a ...combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.
In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg two 300-mg tablets twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival.
The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively).
In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).
Graphene oxide (GO) is reported for the first time as electron shuttle to increase the redox conversion of the azo compound, reactive red 2 (RR2, 0.5mM), and the nitroaromatic, 3-chloronitrobenzene ...(3CNB, 0.5mM). GO (5mgL(-1)) increased 10-fold and 7.6-fold the reduction rate of RR2 and 3CNB, respectively, in abiotic incubations with sulfide (2.6mM) as electron donor. GO also increased by 2-fold and 3.6-fold, the microbial reduction rate of RR2 by anaerobic sludge under methanogenic and sulfate-reducing conditions, respectively. Deep characterization of GO showed that it has a proper size distribution (predominantly between 450 and 700nm) and redox potential (+50.8mV) to promote the reduction of RR2 and 3CNB. Further analysis revealed that biogenic sulfide plays a major role on the GO-mediated reduction of RR2. GO is proposed as an electron shuttle to accelerate the redox conversion of recalcitrant pollutants, such as nitro-benzenes and azo dyes.
ABSTRACT Stars that pass within the Roche radius of a supermassive black hole will be tidally disrupted, yielding a sudden injection of gas close to the black hole horizon which produces an ...electromagnetic flare. A few dozen of these flares have been discovered in recent years, but current observations provide poor constraints on the bolometric luminosity and total accreted mass of these events. Using images from the Wide-field Infrared Survey Explorer, we have discovered transient 3.4 m emission from several previously known tidal disruption flares. The observations can be explained by dust heated to its sublimation temperature due to the intense radiation of the tidal flare. From the break in the infrared light curve we infer that this hot dust is located ∼0.1 pc from the supermassive black hole. Since the dust has been heated by absorbing UV and (potentially) soft X-ray photons of the flare, the reprocessing light curve yields an estimate of the bolometric flare luminosity. For the flare PTF-09ge, we infer that the most likely value of the luminosity integrated over frequencies at which dust can absorb photons is erg s−1, with a factor of 3 uncertainty due to the unknown temperature of the dust. This bolometric luminosity is a factor ∼10 larger than the observed blackbody luminosity. Our work is the first to probe dust in the nuclei of non-active galaxies on sub-parsec scales. The observed infrared luminosity implies a covering factor ∼1% for the nuclear dust in the host galaxies.
A direct pathway to convert orange peels waste to useful co-functionalized carbon quantum dots (CQDs) was performed through a friendly and efficient “greener method” consisting of a one-step ...microwave assisted solvothermal synthesis. The reaction proceeds in a mixture of powder of orange peels as precursor and water. The biomass was characterized by ICP-OES and CHONS analysis together with Fiber's analysis and FT-IR spectroscopy. The prepared CQDs presented a photoluminescent of brightness blue, high aqueous dispersion, chemical stability, an average particle size of 1.16 nm ± 0.1 nm and surface carboxylic and amine groups together with some dopants from the bio-precursor. The Fluorescence study revealed their potential emission in the electromagnetic spectrum of visible light. The bare mesoporous TiO2 semiconductor was impregnated with CQDs and the resultant composites presented a red-shift in the energy band gap with values from 2.3 eV to 2.08 eV, clearly lower than those on bare semiconductor and depending on the amount of CQDs. The CQDs/TiO2 photoelectrodes increased their photocurrent when they were exposed to the UV–Vis light, a decrease of photoelectrochemical band gap energy and an increase of the charge transfer constant in contrast with bare TiO2. These CQDs/TiO2 photoanodes were evaluated in carbon quantum dots-sensitized solar cells (CQDSSC) where there was an increase in the performance of the photovoltaic parameters compared with the bare semiconductor.
Display omitted
The use of composite edible films made from biopolymers has attracted interest as a way to reduce pollution and recycling problems; however, the relation between barrier, mechanical and structural ...properties of the films have been scarcely studied. The aim of this work was to evaluate composite zein–chitosan edible films by applying common nanotechnology tools and to relate the results to zein concentration and film structural changes. Rougher, more elastic, and less hard film structures with better water vapour barrier properties were obtained using larger zein concentrations. Raman spectroscopy exhibited unexpected interactions, as indicated by the disappearance of the thiol groups of cysteine in the zein films and the appearance of OSO and COS groups in the blended materials in conjunction with the disappearance of zein ɛ-amino and NH2 functional groups in the zein film samples, thereby confirming changes in the blended film structure. Zein concentration presented linear correlations with water vapour permeability (R=−0.978) and film roughness (R=0.929). The composite films presented better barrier and mechanical properties than single ingredient films. This information shows the benefit of using protein–polysaccharide blends to prepare edible films.
Natural fiber reinforced composites is an emerging area in polymer science. Fibers derived from annual plants are considered a potential substitute for non-renewable synthetic fibers like glass and ...carbon fibers. The hydrophilic nature of natural fibers affects negatively its adhesion to hydrophobic polymeric matrices. To improve the compatibility between both components a surface modification has been proposed.
The aim of the study is the chemical modification of jute fibers using a fatty acid derivate (oleoyl chloride) to confer hydrophobicity and resistance to biofibers. This reaction was applied in swelling and non-swelling solvents, pyridine and dichloromethane, respectively. The formation of ester groups, resulting from the reaction of oleoyl chloride with hydroxyl group of cellulose were studied by elemental analysis (EA) and Fourier Transform infrared spectroscopy (FTIR). The characterization methods applied has proved the chemical interaction between the cellulosic material and the coupling agent. The extent of the reactions evaluated by elemental analysis was calculated using two ratios. Finally electron microscopy was applied to evaluate the surface changes of cellulose fibers after modification process.
Activated carbons were prepared from spent ground coffee. Zinc chloride was used as an activation agent. The obtained materials were used as a media for separation of hydrogen sulfide from air at ...ambient conditions. The materials were characterized using adsorption of nitrogen, elemental analysis, SEM, FTIR, and thermal analysis. Surface features of the carbons depend on the amount of an activation agent used. Even though the residual inorganic matter takes part in the H₂S retention via salt formation, the porous surface of carbons governs the separation process. The chemical activation method chosen resulted in formation of large volume of pores with sizes between 10 and 30Å, optimal for water and hydrogen sulfide adsorption. Even though the activation process can be optimized/changed, the presence of nitrogen in the precursor (caffeine) is a significant asset of that specific organic waste. Nitrogen functional groups play a catalytic role in hydrogen sulfide oxidation.
Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, ...research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies-including the design and study of hormone secretion and biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.
We present results on the clustering properties of galaxies as a function of both stellar mass and specific star formation rate (sSFR) using data from the PRIMUS and DEEP2 galaxy redshift surveys ...spanning . We use spectroscopic redshifts of over 100,000 galaxies covering an area of 7.2 deg2 over five separate fields on the sky, from which we calculate cosmic variance errors. We find that the galaxy clustering amplitude is as strong of a function of sSFR as of stellar mass, and that at a given sSFR, it does not significantly depend on stellar mass within the range probed here. We further find that within the star-forming population and at a given stellar mass, galaxies above the main sequence of star formation with higher sSFR are less clustered than galaxies below the main sequence with lower sSFR. We also find that within the quiescent population, galaxies with higher sSFR are less clustered than galaxies with lower sSFR, at a given stellar mass. We show that the galaxy clustering amplitude smoothly increases with both increasing stellar mass and decreasing sSFR, implying that galaxies likely evolve across the main sequence, not only along it, before galaxies eventually become quiescent. These results imply that the relation of stellar mass to halo mass, which connects galaxies to dark matter halos, likely depends on sSFR.
Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic ...kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in the PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identify SMPDL3b as a modulator of insulin signaling and demonstrate that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.
PDF
