Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with ...chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis.
In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9.
During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period.
In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen China Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).
► Effect of Al alloy was examined on SLM facilitated in situ interaction with Fe2O3. ► The Al alloy influenced the SLM consolidation performance and the formed phases. ► In situ Al (alloy) composites ...were reinforced by ultrafine/nanoscale particles. ► The Al alloy affected the appearance of reinforced matrix. ► Enhanced solid solubility of matrix contributed to hardening.
This work investigates the effects of various Al alloys (including Al, AlMg1SiCu, and AlSi10Mg), mixed with 15wt% Fe2O3, on the selective laser melting (SLM) facilitated in situ reaction and formation of Al metal matrix composite (MMC) components. The results contribute to the development of medium/high strength Al composite parts which can be produced as complex net-shape products via the SLM process. Visual observation and computed tomography (CT) scanning reveal the best SLM consolidation performance and the lowest porosity for AlSi10Mg. SLM facilitated in situ reaction and subsequent rapid solidification introduce very fine particles (down to ∼50–100nm), reinforcing the microstructure of all Al (alloy) composites. The particles are Al–Fe intermetallics, Al oxides such as α–Al2O3, plus Si crystals (alone or in combination) depending on the alloy composition. Ultrafine/nanoscale dendritic feature appears in the reinforced matrix of AlSi10Mg/15wt%Fe2O3, in contrast with featureless matrix of Al/15wt%Fe2O3. The in situ particle reinforced Al (alloy) composites are significantly harder than corresponding conventionally manufactured (e.g. casting) Al alloys without Fe2O3, due to superior microstructural characteristics such as featureless or very fine dendritic matrix, ultrafine/nanoscale particles, and also enhanced solid solubility of the SLM products.
Batch nitrification tests were conducted with sludge and wastewater streams obtained from field implementations to evaluate nitrification inhibition and efficiency of a nitrifiers bioaugmentation ...technology at full-scale municipal wastewater treatment plants (WWTPs). The results showed that the substrate organic carbon and pH of wastewater streams were inhibitory factors to nitrification and the low pH was the cause of the WWTP experiencing poor nitrification. An ammonia-nitrogen removal rate of 0.21mg-N/gMLVSS-h was observed at pH 6.5, while the rate increased to 0.54mg-N/gMLVSS-h with an introduction of 6% bioaugmented nitrifiers, indicating that the integrated side-stream nitrifiers bioaugmentation process was beneficial in improving nitrification efficiency, even under low pH conditions not conducive to nitrification. The study provides new insights into effective upgrading of municipal WWTPs exposed to poor nitrification.
In the study of lighting, as the construction of a physical test room is costly and time-consuming, researchers have been actively looking for alternative media to present physical environments. ...Virtual reality, photo and video are the most commonly used approaches in the lighting community, and they have all been used by researchers around the world. Most such studies have been conducted without discussing what gives the subjects a better sense of realism, presence, etc., and which type of media is closer to the ideal, the physical lighting environment. In this paper, we aim to select the optimal alternative media that can present physical lighting environments. We compare a human’s subjective feeling towards a physical lighting environment and three alternative reproduction technologies, namely, virtual reality reproduction, video reproduction and photographic reproduction. We also discuss the feasibility of using virtual reality in representing lighting environments. The selection of the most optimal media is based on the perceptual attributes of lighted space, and the findings are only related to these criteria. The main results of this study are the following:
(a) The order of the overall presentation-ability of the media is physical space > virtual reality reproductions > video reproductions > photo reproductions.
(b) In terms of subjective rating, virtual reality lighting environments are rated closest to the physical lighting environments, and the order of the approximate coefficient of the media is physical space (1) > VR reproductions (0.886) > video reproductions (0.752) > photo reproductions (0.679).
(c) Virtual reality can present lighting attributes of open/close, diffuse/glaring, bright/dim and noisy/quiet consistent with the physical environment.
(d) Human subjects are most satisfied with VR reproductions.
Previous studies have established the link between aberrant microRNA (miRNA) expression and hypoxia in various neoplasms. However, how these hypoxia-related miRNAs modulate tumor progression is still ...unclear. Therefore, the patterns of miRNA in colorectal carcinoma cell lines in response to hypoxia or not were first screened and the hypoxia-induced repression of the miR-15-16 cluster was confirmed. Then, this repression was found to be associated with high tumor stage and poor prognosis in colorectal carcinoma and is shown to promote tumor angiogenesis and metastasis by the loss of restriction of its target gene, fibroblast growth factor-2 (FGF2). Moreover, the general and alterative promoters of the miR-15-16 host (deleted in lymphocytic leukemia 2, DLEU2) were mapped, and three c-Myc/Max binding sites in response to the hypoxia-induced repression of miR-15-16 were further identified. Finally, an enhanced stability of c-Myc/Max heterodimer promoted by increased hypoxia-inducible factor-2α (HIF-2α) was validated, and we also verified that the enhancement contributed to the hypoxia-induced repression of miR-15-16. In brief, the c-Myc-mediated transcriptional repression of miR-15-16 in hypoxia is induced by increased HIF-2α and promoted tumor angiogenesis and hematogenous metastasis by the further loss of post-transcriptional inhibition of FGF2. Our study provides a better understanding of the coping mechanisms in response to tumor hypoxia and may be helpful in developing an effective prognostic marker or treatment target against solid tumors.
Support structures are required in several additive manufacturing (AM) processes to sustain overhanging parts, in particular for the production of metal components. Supports are typically hollow or ...cellular structures to be removed after metallic AM, thus they represent a considerable waste in terms of material, energy and time employed for their construction and removal. This study presents a new approach to the design of support structures that optimise the part built orientation and the support cellular structure. This approach applies a new optimisation algorithm to use pure mathematical 3D implicit functions for the design and generation of the cellular support structures including graded supports. The implicit function approach for support structure design has been proved to be very versatile, as it allows geometries to be simply designed by pure mathematical expressions. This way, different cellular structures can be easily defined and optimised, in particular to have graded structures providing more robust support where the object’s weight concentrate, and less support elsewhere. Evaluation of support optimisation for a complex shape geometry revealed that the new approach presented can achieve significant materials savings, thus increasing the sustainability and efficiency of metallic AM.
The effect of COD:N ratio on sludge properties and their role in membrane fouling were examined using a well-controlled aerobic membrane bioreactor receiving a synthetic high strength wastewater ...containing glucose. Membrane performance was improved with an increase in the COD/N ratio (100:5–100:1.8) (i.e. reduced N dosage). Surface analysis of sludge by X-ray photoelectron spectroscopy (XPS) indicates significant differences in surface concentrations of elements C, O and N that were observed under different COD/N ratios, implying changes in the composition of extracellular polymeric substances (EPS). Fourier transform-infrared spectroscopy (FTIR) revealed a unique characteristic peak (CO bonds) at 1735 cm−1 under nitrogen limitation conditions. Total EPS decreased with an increase in COD/N ratio, corresponding to a decrease in the proteins (PN) to carbohydrates (CH) ratio in EPS. There were no significant differences in the total soluble microbial products (SMPs) but the ratio of PN/CH in SMPs decreased with an increase in COD/N ratios. The results suggest that EPS and SMP composition and the presence of a small quantity of filamentous microorganisms played an important role in controlling membrane fouling.
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•An increase in COD:N ratio led to improved membrane performance.•Surface concentrations of elements O and N and C bonds are different under different COD:N ratios.•Bound EPS/SMP composition is more important than the quantity in controlling membrane fouling.•The presence of a small quantity of filamentous microorganisms led to improved membrane performance.•A characteristic peak of FTIR at 1735 cm−1 was observed for sludge under N deficiency.
SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and ...precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.
A facile method to prepare carbon nanotube/carbon fiber hybrid fiber was explored by combining electrophoretic deposition process with sizing process. The electrophoretic deposition was conducted in ...acid-treated carbon nanotube/N, N-dimethylformamide suspension with an annular electrode which made the electrophoretic deposition effective. Sizing process was performed using a thermoplastic sizing agent after the electrophoretic deposition. Carbon nanotubes were deposited on the carbon–fiber surface and were tightly attached to it. The wetting performance of hybrid fiber was significantly enhanced by polymer matrix. Meanwhile, the introduction of carbon nanotubes in the carbon fiber reinforced thermoplastic composites results in a 35.6% enhancement in the interfacial shear strength. Such a fabrication process is easy, effective and can be a continuous one for industrial scale.
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