This randomized, phase 3 trial compared the effectiveness of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, with epoetin alfa in patients undergoing hemodialysis or ...peritoneal dialysis in China. Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia.
This phase 3, randomized trial in China compared the efficacy and safety of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, with placebo for anemia in patients with CKD who ...were not undergoing dialysis. Roxadustat was superior to placebo in increasing and maintaining hemoglobin levels.
Artificial neuronal devices are critical building blocks of neuromorphic computing systems and currently the subject of intense research motivated by application needs from new computing technology ...and more realistic brain emulation. Researchers have proposed a range of device concepts that can mimic neuronal dynamics and functions. Although the switching physics and device structures of these artificial neurons are largely different, their behaviors can be described by several neuron models in a more unified manner. In this paper, the reports of artificial neuronal devices based on emerging volatile switching materials are reviewed from the perspective of the demonstrated neuron models, with a focus on the neuronal functions implemented in these devices and the exploitation of these functions for computational and sensing applications. Furthermore, the neuroscience inspirations and engineering methods to enrich the neuronal dynamics that remain to be implemented in artificial neuronal devices and networks toward realizing the full functionalities of biological neurons are discussed.
Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were ...previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora. Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.
Codon usage bias is a universal feature of eukaryotic and prokaryotic genomes and has been proposed to regulate translation efficiency, accuracy, and protein folding based on the assumption that ...codon usage affects translation dynamics. The roles of codon usage in translation, however, are not clear and have been challenged by recent ribosome profiling studies. Here we used a Neurospora cell-free translation system to directly monitor the velocity of mRNA translation. We demonstrated that the preferred codons enhance the rate of translation elongation, whereas non-optimal codons slow elongation. Codon usage also controls ribosome traffic on mRNA. These conclusions were supported by ribosome profiling results in vitro and in vivo with template mRNAs designed to increase the signal-to-noise ratio. Finally, we demonstrate that codon usage regulates protein function by affecting co-translational protein folding. These results resolve a long-standing fundamental question and suggest the existence of a codon usage code for protein folding.
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•The velocity of mRNA translation is monitored using a cell-free system•Preferred codons enhance the elongation rate, whereas non-optimal codons reduce it•Ribosome profiling results confirm the role of codon usage in elongation•Codon usage regulates protein function by affecting co-translational protein folding
Yu et al. demonstrate that codon usage impacts local translational dynamics: frequently used codons speed up elongation, while non-preferred codons slow it down. The changes of translation elongation rates on mRNAs are adapted to protein structures to facilitate co-translational folding. The results suggest a codon usage “code” for protein structure.
The TreeFET channel, which is a combination of vertically stacked nanosheet channels and fin-shaped interbridge channels in between the nanosheets, can provide an additional channel conduction area ...to improve the on-current without increasing the device footprint. To provide on-current enhancement, a minimum height is required for the interbridge that is dependent on the width of the interbridge and the physical gate oxide thickness. Minimizing the threshold voltage difference between the interbridges and the nanosheet channels also plays a crucial role in the optimization of the on-current of TreeFETs. The design criteria for TreeFETs are studied using TCAD simulation of Ge nFETs.
Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal ...lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn
of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis.
Nitrogen is an essential element for plant growth and development; however, due to environmental pollution, high nitrate concentrations accumulate in the edible parts of these leafy vegetables, ...particularly if excessive nitrogen fertilizer has been applied. Consuming these crops can harm human health; thus, developing a suitable strategy for the agricultural application of nitrogen fertilizer is important. Organic, inorganic, and liquid fertilizers were utilized in this study to investigate their effect on nitrate concentrations and lettuce growth. The results of this pot experiment show that the total nitrogen concentration in soil and the nitrate concentration in lettuce increased as the amount of nitrogen fertilizer increased. If the recommended amount of inorganic fertilizer (200 kg·N·ha⁻¹) is used as a standard of comparison, lettuce augmented with organic fertilizers (200 kg·N·ha⁻¹) have significantly longer and wider leaves, higher shoot, and lower concentrations of nitrate.
This study introduces a recent field experiment investigating multiscale terrain–circulation–precipitation interactions. When a synoptic‐scale northeasterly wind prevails under the active East Asian ...winter monsoon, stratocumulus cloud decks with severe rainfall exceeding 100 mm·day−1 frequently occur in the northeastern plain area and adjacent mountains in Yilan, Taiwan. The Yilan Experiment of Severe Rainfall (YESR2020) is a field campaign from November 20, 2020, to November 24, 2020, to survey the physical processes leading to severe wintertime rainfall. The three‐dimensional structure of the wind field and the atmospheric environment can be identified through high temporal and spatial resolution sounding observations, which is empowered by the novel Storm Tracker mini‐radiosonde. During YESR2020, the continuously collected meteorological data of two northeasterly episodes captured the variability of local‐scale wind patterns and the features of the severe rainfall induced by stratocumulus. A preliminary analysis indicated that a local‐scale convergence line could appear over the plain area of Yilan under the northeasterly environmental condition. The precipitation hotspot was located in the mountain region of southern Yilan, where the local winds signified turbulence features. Moreover, the severe rainfall of the two northeasterly episodes spotlighted shallow cumulus under stratus with pure warm rain processes. The results of YESR2020 inspire the arrangement of future field observations to explore detailed mechanisms of heavily precipitating stratocumulus over complex topography.
We conducted the Yilan Experiment of Severe Rainfall (YESR2020) to survey physical processes leading to severe rainfall in the northeastern plain area and adjacent mountains in Yilan, Taiwan, when a synoptic‐scale northeasterly wind prevails under the active East Asian winter monsoon with stratocumulus cloud decks. A preliminary analysis indicated that a local‐scale convergence line appeared over the plain area, and the precipitation hotspot was located in the mountain region of southern Yilan, where turbulence features were apparent. The results inspire the arrangement of future field observations to explore mechanisms of heavily precipitating stratocumulus over complex topography.
Thrombospondin‐1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia‐induced damages and wound‐healing activity in human corneal ...epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography‐tandem mass spectrometry, and HCE cell migration and motility were examined through wound‐healing assay and time‐lapse microscopy. Reestablishment of cell junctions by TSP1 was assessed through confocal microscopy and 3D image reconstruction. Our results show that CoCl2‐induced hypoxia promoted HCE cell death by paraptosis. TSP1 protected these cells against paraptosis by attenuating mitochondrial membrane potential depletion, swelling and dilation of endoplasmic reticulum and mitochondria, and mitochondrial fission. Exosomes isolated from HCE cells treated with TSP1 contained wound healing‐associated proteins that were taken up by HCE cells to promote tissue remodeling and repair. TSP1 protected HCE cells against hypoxia‐induced damages and inhibited paraptosis progression by promoting cell migration, cell‐cell adhesion, and extracellular matrix remodeling. These findings indicate that TSP1 ameliorates hypoxia‐induced paraptosis in HCE cells and promotes wound healing and remodeling by regulating exosomal protein expression. TSP1 may, therefore, play important roles in the treatment of hypoxia‐associated corneal diseases.
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