Dysregulation of miRNA expression is correlated with the development and progression of many diseases. These miRNAs are regarded as promising biomarkers. However, it is challenging to measure these ...low abundant molecules without employing time-consuming radioactive labeling or complex amplification strategies. Here, we present a DNA logic gate platform for miRNA diagnostics with fluorescence outputs from near-infrared (NIR) Ag2S quantum dots (QDs). Carefully designed toehold exchange-mediated strand displacements with different miRNA inputs occur on a solid-state interface, which control QDs release from solid-state interface to solution, responding to multiplex information on initial miRNAs. Excellent fluorescence emission properties of NIR Ag2S QDs certify the great prospect for amplification-free and sensitive miRNA assay. We demonstrate the potential of this platform by achieving femtomolar level miRNA analysis and the versatility of a series of logic circuits computation.
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ...ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model.
Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress.
These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.
As the most prevalent physical activity and transportation mode for older people, walking is considered to have multiple health and well‐being benefits. Previous studies used separate models to ...assess the built‐environment determinants of a battery of walking behavior measures, such as walking frequency and duration. In a departure from them, this study develops a system of equations, which is estimated by seemingly unrelated regression, to determine the built‐environment factors that significantly influence two correlated walking behavior measures (including walking frequency and duration) of older adults in Xiamen (a medium‐sized Chinese city) based on data from the Travel Survey of Xiamen Residents 2015 and built‐environment geo‐data. The results show the following: (1) the walking frequency and duration of older adults are affected by the built environment and socio‐demographic characteristics; (2) land‐use mix, intersection density, and bus route density positively influence older adults’ walking frequency and duration; (3) distance to the commercial center adversely impacts the walking frequency and duration; and (4) the built environment has similar effects on the two measures. This study offers a worthwhile reference for policy intervention to promote older adults' walking activities, thereby contributing to active and healthy aging.
Many countries have been implementing various control measures with different strictness levels to prevent the coronavirus disease 2019 (COVID-19) from spreading. With the great reduction in human ...mobility and daily activities, considerable impacts have been imposed on the global air transportation industry. This study applies a hybrid SARIMA-based intervention model to measure the differences in the impacts of different control measures implemented in China, the U.S. and Singapore on air passenger and air freight traffic. To explore the effect of time span for the measures to be in force, two scenarios are invented, namely a long-term intervention and a short-term intervention, and predictions are made till the end of 2020 for all three countries under both scenarios. As a result, predictive patterns of the selected metrics for the three countries are rather different. China is predicted to have the mildest economic impact on the air transportation industry in this year in terms of air passenger revenue and air cargo traffic, provided that the control measures were prompt and effective. The U.S. would suffer from a far-reaching impact on the industry if the same control measures are maintained. More uncertainties are found for Singapore, as it is strongly associated with international travel demands. Suggestions are made for the three countries and the rest of the world on how to seek a balance between the strictness of control measures and the potential long-term industrial losses.
Increasing evidence suggests that the metabolism of lipids plays a crucial role in the progression of gastric cancer. However, the expression of lipid metabolism-related genes (LMGs) still does not ...serve as a prognostic biomarker in gastric cancer. We obtained transcriptome data for 751 LMGs and divided STAD patients into two subtypes based on differences in LMGs expression. Then, we analyzed genetic changes in two subtypes as well as immune features to determine their differences. We also constructed a prognostic risk model related to LMGs for individualized comprehensive evaluations. In this study, two lipid metabolic (LM) subtypes were identified anchored in the expression profiles of LMGs. Clinical information, genomic alterations, immune features, and immunotherapy response varied significantly between the two LM subtypes. A risk model based on LMGs was also developed to assess prognosis and distinguish patients with high risk from those at low risk. The prognosis differed significantly between the two risk groups of patients. In STAD patients, the risk score was strongly correlated with genomic alterations and immune profile scores. Also, the risk score was an excellent predictor of immune checkpoint inhibitors (ICIs) response. Anchored in preliminary results derived from the aforementioned bioinformatic analysis, we chose CYP19A1 as our target gene and the expression of CYP19A1 was verified in several common gastric cancer cell lines. Then, we carried out the Western blotting, CCK-8 assay, colony formation assay, wound healing assay, and transwell assay to explore the effects of CYP19A1 on malignant biological behavior, and positive consequences were obtained. In this study, STAD patients were divided into two subtypes based on LMGs expression. It is possible to assess the prognosis of a patient and the response to immunotherapy using the established prognostic risk model. A series of basic laboratory experiments also verified the functional role of CYP19A1 in gastric cancer.
In the field of vehicle system dynamics, it is significant to propose an appropriate quantitative indicator for system stability or dynamics characteristics. Lyapunov exponents method is an excellent ...quantitative indicator for analysing nonlinear system characteristics. It was used to studied the stable region of nonlinear vehicle plane motion system. However, the effect of Lyapunov exponents method in revealing the global dynamics characteristics has not been fully studied. Aiming at this key problem, this paper analyses the global characteristics of Lyapunov exponents with different degrees of freedom nonlinear models. The results show that Lyapunov exponents can well reflect the global layer characteristics for vehicle system. However, the value characteristic under different DOF models is not unified. The research and analysis in this paper supplement the quantitative analysis theory for vehicle system dynamics.
Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein ...expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured "superfolder" mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) can measure deoxyhemoglobin content. This study aims to evaluate the capacity of BOLD-MRI, which is possible to evaluate the ...oxygenation state of kidneys with renal artery stenosis (RAS).
We performed BOLD-MRI for 40 patients with RAS and for 30 healthy volunteers. We then performed post-scan processing and analysis of manually drawn regions of interest to determine R2* values (relaxation rates) for the renal cortex and medulla. We compared R2* values in patients with RAS with those in the control group, and also compared these values for subgroups with varying degrees of stenosis.
Medulla R2* values were higher than cortex R2* values in the control group. There was no significant difference in R2* values for different segments (upper, middle, lower) of the kidneys. Both cortex and medulla R2* values in patients with RAS were significantly higher than corresponding R2* values in the control group (P < 0.05), and BOLD-MRI was more sensitive to changes in the R2* values in the medulla than in the cortex. Among different subgroups in the RAS group, the medulla R2* values were significantly higher in kidneys with severe stenosis than in those with no obvious obstruction, mild stenosis, or moderate stenosis (P < 0.05).
BOLD-MRI is an effective, noninvasive method for evaluating kidney oxygenation, which is important for proper treatment in RAS. It is sufficiently sensitive for detecting medulla ischemia and anoxia of the kidneys.
When auralizing moving sound sources in Virtual Reality (VR) environments, the two main input parameters are the location and radiated signal of the source. An array measurement-based model is ...developed to characterize moving sound sources regarding the two parameters in this thesis. This model utilizes beamforming, i.e. delay and sum beamforming (DSB) and compressive beamforming (CB) to obtain the locations and signals of moving sound sources. A spiral and a pseudorandom microphone array are designed for DSB and CB, respectively, to yield good localization ability and meet the requirement of CB. The de-Dopplerization technique is incorporated in the time-domain DSB to address moving source problems. Time-domain transfer functions (TDTFs) are calculated in terms of the spatial locations within the steering window of the moving source. TDTFs then form the sensing matrix of CB, thus allowing CB to solve moving source problem. DSB and CB are further extended to localize moving sound sources, and the reconstructed signals from the beamforming outputs are investigated to obtain the source signals. Moreover, localization and signal reconstruction are evaluated through varying parameters in the beamforming procedures, i.e. steering position, steering window length and source speed for a moving periodic signal using DSB, and regularization parameter, signal to noise ratio (SNR), steering window length, source speed, array to source motion trajectory and mismatch for a moving engine signal using CB. The parameter studies show guidelines of parameter selection based on the given situations in this thesis for modeling moving source using beamforming. Both algorithms are able to reconstruct the moving signals in the given scenarios. Although CB outperforms DSB in terms of signal reconstruction under particular conditions, the localization abilities of the two algorithms are quite similar. The practicability of the model has been applied on pass-by measurements of a moving loudspeaker using the designed arrays, and the results can match the conclusions drawn above from simulations. Finally, a framework on how to apply the model for moving source auralization is proposed.
Abstract
Oxidation of renewable polyol/sugar into formic acid using molecular O
2
over heterogeneous catalysts is still challenging due to the insufficient activation of both O
2
and organic ...substrates on coordination-saturated metal oxides. In this study, we develop a defective MnO
2
catalyst through a coordination number reduction strategy to enhance the aerobic oxidation of various polyols/sugars to formic acid. Compared to common MnO
2
, the tri-coordinated Mn in the defective MnO
2
catalyst displays the electronic reconstruction of surface oxygen charge state and rich surface oxygen vacancies. These oxygen vacancies create more Mn
δ+
Lewis acid site together with nearby oxygen as Lewis base sites. This combined structure behaves much like Frustrated Lewis pairs, serving to facilitate the activation of O
2
, as well as C–C and C–H bonds. As a result, the defective MnO
2
catalyst shows high catalytic activity (turnover frequency: 113.5 h
−1
) and formic acid yield (>80%) comparable to noble metal catalysts for glycerol oxidation. The catalytic system is further extended to the oxidation of other polyols/sugars to formic acid with excellent catalytic performance.
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