Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in blindness in bilateral eyes. ...Various photoreceptor cell death types and pathological phenotypic changes that have been disclosed in RP demand in-depth research of its pathogenic mechanism that may account for inter-patient heterogeneous responses to mainstream drug treatment. As the primary method for studying the genetic characteristics of RP, molecular biology has been widely used in disease diagnosis and clinical trials. Current technology iterations, such as gene therapy, stem cell therapy, and optogenetics, are advancing towards precise diagnosis and clinical applications. Specifically, technologies, such as effective delivery vectors, CRISPR/Cas9 technology, and iPSC-based cell transplantation, hasten the pace of personalized precision medicine in RP. The combination of conventional therapy and state-of-the-art medication is promising in revolutionizing RP treatment strategies. This article provides an overview of the latest research on the pathogenesis, diagnosis, and treatment of retinitis pigmentosa, aiming for a convenient reference of what has been achieved so far.
Neural machine translation (NMT) is applied to generate a more reliable and accurate translation practice as the most cutting-edge technology. In recent years, NMT has achieved gratifying results. ...However, the main obstacle for market-oriented NMT application systems appears to suffer from weak translation quality that fails to meet users' needs. This paper focuses on the machine translation of political documents and implements six dominant NMT application systems in the market to evaluate their translation quality. The evaluation process further employs both BLEU and NIST technical evaluation algorithms and re-verifies the results with the manual evaluation method called the "Score Ranking System" to compare the performances of the six NMTs in Chinese-English translations of political documents. Through diagnosis and evaluation of the problems and errors in NMTs, the paper eventually proposes the "Cue Lexicon+" model to remedy prominent problems. Besides, the "NMT+ Lexicon Intelligent Translation Assistant" soft is developed and the "Cue Lexicon+" is integrated into the NMT application systems to further improve the translation quality, providing a reference and research basis to increase the performance and update the NMT application systems.
Double-node upsets induced by the charge sharing effects are emerging as a major reliability issue in nanometer latch design. Although the existing robust latches can provide a good tolerance for ...double-node upsets, the implementation of these hardened latches incurs in considerable hardware penalties in terms of delay, area, and power, because they rely on traditional hardening techniques such as space redundancy. In this paper, a novel low-complexity (with respect to hardware redundancy in terms of area, delay, and power) radiation hardened (RH) latch is proposed; this latch is based on the dual interlocked storage cell (DICE). Based on the radiation upset mechanism, in particular the upset polarity of the transient pulse, the proposed RH latch can effectively reduce the number of protected nodes (sensitive nodes), as well as the number of transistors, thus reducing circuit overhead. At the same, a single node upset in any sensitive node and a double-node upset in any sensitive node pair can be recovered, because at least two stable nodes can retain the values even when a double-node upset occurs. The results are based on mapping designs to TSMC 65 nm commercial CMOS process design kit (PDK) and demonstrate that the proposed RH latch incurs in significant reductions in terms of propagation delay, circuit area, and power-delay-area product (PDAP), compared with existing hardened latches. The tolerance functionality of the proposed latch is successfully validated by fault injection. In addition, the impact of variations and process corners is assessed using Monte Carlo (MC) simulation. The simulation results confirm that the proposed latch can also tolerate all upsets, even under extreme values of process variations.
In this work, a novel colorimetric assay based on polythiophene derivative (PMNT) was designed for the detection of protein kinase A (PKA). PKA can catalyze the phosphorylation of peptide, leading to ...the conformation change of PMNT from random-coil to planar, with the disappearance of absorption peaks above 500 nm and a color change from pink to yellow. The fabricated assay exhibits a wide linear range of 0.05 – 20 U/mL with a detection limit of 0.02 U/mL for PKA activity detection. The proposed protocol has promising prospects for use in clinical diagnosis related to PKA activity.
Machine reading comprehension (MRC), which requires a machine to answer questions based on a given context, has attracted increasing attention with the incorporation of various deep-learning ...techniques over the past few years. Although research on MRC based on deep learning is flourishing, there remains a lack of a comprehensive survey summarizing existing approaches and recent trends, which motivated the work presented in this article. Specifically, we give a thorough review of this research field, covering different aspects including (1) typical MRC tasks: their definitions, differences, and representative datasets; (2) the general architecture of neural MRC: the main modules and prevalent approaches to each; and (3) new trends: some emerging areas in neural MRC as well as the corresponding challenges. Finally, considering what has been achieved so far, the survey also envisages what the future may hold by discussing the open issues left to be addressed.
Peanut (
L.) is one of the five major oilseed crops cultivated worldwide. Salt stress is a common adverse condition for the growth of this crop in many countries and regions. In this study, ...physiological parameters and transcriptome profiles of peanut seedlings exposed to salt stress (250 mM NaCl for 4 days, S4) and recovery for 3 days (when transferred to standard conditions for 3 days, R3) were analyzed to detect genes associated with salt stress and recovery in peanut. We observed that the quantum yield of PSII electron transport (ΦPSII) and the maximal photochemical efficiency of PSII (
/
) decreased in S4 compared with the control, and increased in R3 compared with those in S4. Seedling fresh weight, dry weight and PSI oxidoreductive activity (Δ
/
) were inhibited in S4 and did not recover in R3. Superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities decreased in S4 and increased in R3, whereas superoxide anion (Formula: see text) and hydrogen peroxide (H
O
) contents increased in S4 and decreased in R3. Transcriptome analysis revealed 1,742 differentially expressed genes (DEGs) under salt stress and 390 DEGs under recovery. Among these DEGs, two DEGs encoding ω-3 fatty acid desaturase that synthesized linolenic acid (18:3) from linoleic acid (18:2) were down-regulated in S4 and up-regulated in R3. Furthermore, ω-3 fatty acid desaturase activity decreased under salt stress and increased under recovery. Consistent with this result, 18:3 content decreased under salt stress and increased under recovery compared with that under salt treatment. In conclusion, salt stress markedly changed the activity of ω-3 fatty acid desaturase and fatty acid composition. The findings provide novel insights for the improvement of salt tolerance in peanut.
The association between obesity and respiratory diseases has been confirmed. However, few studies have reported the relationship between obesity and the risk and mortality of chronic inflammatory ...airway disease (CIAD). The aim of this study was to reveal the association between obesity and the risk of CIAD, and mortality in patients with CIAD.
The study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 among adults aged 20 years and above. All participants were grouped according to body mass index (BMI) and waist circumference (WC) levels to study the relationship between obesity and CIAD. Multivariate logistic regression analysis was utilized to examine the connection between CIAD and obesity in a cross-sectional study. The association between obesity and all-cause mortality in individuals with CIAD was examined using multiple cox regression models and smooth curve fitting in a prospective cohort study.
When stratified based on BMI in comparison to the normal weight group, the ORs with 95%CIs of CIAD for underweight and obesity were 1.39 (1.01-1.93) and 1.42 (1.27-1.58), respectively. The OR with 95%CI of CIAD for obesity was 1.20 (1.09-1.31) when stratified according to WC. Additionally, underweight was associated with a higher mortality (HR = 2.44, 95% CI = 1.31-4.55), whereas overweight (HR = 0.58,95% CI = 0.39-0.87) and obesity (HR = 0.59,95% CI = 0.4-0.87) were associated with a lower mortality (P for trend < 0.05). There was a non-linear association between BMI and all-cause mortality (P for non-linear = 0.001). An analysis of a segmentation regression model between BMI and all-cause mortality revealed a BMI turning point value of 32.4 kg/m
. The mortality of CIAD patients was lowest when BMI was 32.4 kg/m
. When BMI ≤ 32.4 kg/m
, BMI was inversely associated with all-cause mortality in patients with CIAD (HR: 0.92, 95%CI:0.88-0.97). However, when BMI > 32.4 kg/m
, there was no association between BMI and all-cause mortality (HR:1.02, 95%CI:0.97-1.06).
Compared to normal weight, underweight and obesity were associated with the increased risk of CIAD. Underweight was associated with increased all-cause mortality, while overweight was associated with reduced all-cause mortality. There was a non-linear association between BMI and all-cause mortality in patients with CIAD. The all-cause mortality was lowest when BMI was 32.4 kg/m
.
Abstract
Owing to the coupling between open Fermi arcs on opposite surfaces, topological Dirac semimetals exhibit a new type of cyclotron orbit in the surface states known as Weyl orbit. Here, by ...lowering the carrier density in Cd
3
As
2
nanoplates, we observe a crossover from multiple-frequency to single-frequency Shubnikov–de Haas (SdH) oscillations when subjected to out-of-plane magnetic field, indicating the dominant role of surface transport. With the increase of magnetic field, the SdH oscillations further develop into quantum Hall state with non-vanishing longitudinal resistance. By tracking the oscillation frequency and Hall plateau, we observe a Zeeman-related splitting and extract the Landau level index as well as sub-band number. Different from conventional two-dimensional systems, this unique quantum Hall effect may be related to the quantized version of Weyl orbits. Our results call for further investigations into the exotic quantum Hall states in the low-dimensional structure of topological semimetals.
CD/CS-SCU-NPs were prepared by ionic cross-linking method. Orthogonal design was used to optimize the formulation. The optimum formulation was tested in vitro and in vivo.
Epilepsy is considered as a ...common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs). The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ) intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm) with high drug loading (around 35%) and high entrapment efficiency (around 80%). The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.
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