In recent years, a common-used antidiabetic drug, liraglutide, was identified with extra effects on lipid metabolism. Its effects against excessive lipid deposition in bone marrow were gained much ...attention but not well established. Our aim in the present study is to explore the interaction of miRNAs-mRNAs altered by liraglutide administration during bone marrow adipogenesis in diabetes. To establish the diabetic animal model, rats were treated with high fat diet (HFD) and STZ injection. We then identified the lowering effect of liraglutide on lipids metabolism in the diabetes. During this process, high-throughput sequencing and bioinformatics analyses on miRNAs extracted from bone marrow mesenchymal stem cells (BMSCs) were conducted after liraglutide administration. We then identified five differentially expressed miRNAs (miRNA-150-5p, miRNA-129-5p, miRNA-201-3p, miRNA-201-5p, and miRNA-214-5p). The expressions of the DE miRNAs were verified as temporal specific expression patterns in Day 3 and in Day 7. Among them, miRNA-150-5p expression was more stable and consistent with the sequencing data. Of interest, miR-150-5p overexpression facilitated adipogenesis of BMSCs. But this promotion was alleviated by liraglutide. The predicted target gene of miR-150-5p, GDF11, was validated to be involved in liraglutide alleviated BMSCs’ lipid accumulation in diabetes. In vitro, liraglutide increased the GDF11 expression, rescued its down-expression by siGDF11 and inhibit the adipogenesis of BMSCs cultured in high glucose medium. In vivo, liraglutide reversed the HFD-STZ induced excessive lipid droplets by up-regulation of GDF11 expression, which was discounted by agomiR-150-5p injection. Above all, liraglutide might alleviate bone marrow fat accumulation via inactivating miR-150-5p/GDF11 axis in diabetes.
Shoot branching is one of the important agronomic traits affecting yields and quality of tea plant (Camellia sinensis). Cytokinins (CTKs) play critical roles in regulating shoot branching. However, ...whether and how differently alternative splicing (AS) variant of CTKs-related genes can influence shoot branching of tea plant is still not fully elucidated.
In this study, five AS variants of CTK biosynthetic gene adenylate isopentenyltransferase (CsA-IPT5) with different 3' untranslated region (3' UTR) and 5' UTR from tea plant were cloned and investigated for their regulatory effects. Transient expression assays showed that there were significant negative correlations between CsA-IPT5 protein expression, mRNA expression of CsA-IPT5 AS variants and the number of ATTTA motifs, respectively. Shoot branching processes induced by exogenous 6-BA or pruning were studied, where CsA-IPT5 was demonstrated to regulate protein synthesis of CsA-IPT5, as well as the biosynthesis of trans-zeatin (tZ)- and isopentenyladenine (iP)-CTKs, through transcriptionally changing ratios of its five AS variants in these processes. Furthermore, the 3' UTR AS variant 2 (3AS2) might act as the predominant AS transcript.
Together, our results indicate that 3AS2 of the CsA-IPT5 gene is potential in regulating shoot branching of tea plant and provides a gene resource for improving the plant-type of woody plants.
•An asynchronous fault location method based transient traveling wave data fusion.•Refraction and attenuation which affect traveling wave amplitude are considered.•A reasonable measuring ...configuration is suitable for real power grids.•The method is validated by simulating IEEE 30-bus test system.
Considering the complex topology of power grids and their important application, finding an effective fault location algorithm is mandatory. This paper presents a fault location method for power grid based on transient travelling wave data fusion and asynchronous voltage measurements. Firstly, the refraction regularity, attenuation rule and main factors affecting the amplitude of the initial travelling wave are analyzed. Then the modulus maxima of detail coefficients, treated as the feature variables of the initial travelling wave, are extracted via wavelet transform. At last, according to the configuration of the measuring points, fault location scheme based on data fusion theory is proposed. In data level fusion, phase-mode and wavelet transform are carried out in order to obtain the feature variables. In feature level fusion, the fault section is determined through the fault feature variables filtered by the network topology and the artificial neural network is used to fit the relationship between the fault distance and the time difference of arrival between single-terminal aerial-mode and zero-mode voltage. In decision level fusion, the double-terminal fault location algorithm based on the single-ended uploaded data is proposed. The IEEE 30-Bus System is simulated in PSCAD/EMTDC and the fault location algorithm is carried out in MATLAB. The simulation results demonstrate that high-precision fault location could be realized and that practicality and economy are improved without requirements on synchronous sampling.
Development of novel activable dual-mode T
/T
-weighted magnetic resonance (MR) contrast agents with the same composition for dynamic precision imaging of tumors has been a challenging task. Here, we ...demonstrated a strategy to prepare clustered Fe
O
nanoparticles (NPs) with redox-responsiveness to tumor microenvironment to achieve switchable T
/T
-weighted dual-mode MR imaging applications. In this study, we first synthesized ultrasmall Fe
O
NPs with an average size of 3.3 nm and an
relaxivity of 4.3 mM
s
, and then cross-linked the single Fe
O
NPs using cystamine dihydrochloride (Cys) to form clustered Fe
O
/Cys NPs. The Fe
O
nanoclusters (NCs) possess desirable colloidal stability, cytocompatibility, high
relaxivity (26.4 mM
s
), and improved cellular uptake efficiency. Importantly, with the redox-responsiveness of the disulfide bond of Cys, the Fe
O
NCs can be dissociated to form single particles under a reducing condition, hence displaying a switchable T
/T
-weighted MR imaging property that can be utilized for dynamic precision imaging of cancer cells
and a subcutaneous tumor model
due to the reductive intracellular environment of cancer cells and the tumor microenvironment. With the tumor reductive microenvironment-mediated switching of T
to T
MR effect and the ultrasmall size of the single particles that can pass through the kidney filter, the developed Fe
O
NCs may be used as a promising switchable T
/T
dual-mode MR contrast agent for precision imaging of different biosystems.
Development of novel activable dual-mode T1/T2-weighted magnetic resonance (MR) contrast agents with the same composition for dynamic precision imaging of tumors has been a challenging task. Here, we ...demonstrated a strategy to prepare clustered Fe3O4 nanoparticles (NPs) with redox-responsiveness to tumor microenvironment to achieve switchable T2/T1-weighted dual-mode MR imaging applications. In this study, we first synthesized ultrasmall Fe3O4 NPs with an average size of 3.3 nm and an r 1 relaxivity of 4.3 mM–1 s–1, and then cross-linked the single Fe3O4 NPs using cystamine dihydrochloride (Cys) to form clustered Fe3O4/Cys NPs. The Fe3O4 nanoclusters (NCs) possess desirable colloidal stability, cytocompatibility, high r 2 relaxivity (26.4 mM–1 s–1), and improved cellular uptake efficiency. Importantly, with the redox-responsiveness of the disulfide bond of Cys, the Fe3O4 NCs can be dissociated to form single particles under a reducing condition, hence displaying a switchable T2/T1-weighted MR imaging property that can be utilized for dynamic precision imaging of cancer cells in vitro and a subcutaneous tumor model in vivo due to the reductive intracellular environment of cancer cells and the tumor microenvironment. With the tumor reductive microenvironment-mediated switching of T2 to T1 MR effect and the ultrasmall size of the single particles that can pass through the kidney filter, the developed Fe3O4 NCs may be used as a promising switchable T2/T1 dual-mode MR contrast agent for precision imaging of different biosystems.
Polyhydroxyalkanoates (PHAs), a biodegradable plastic that might replace petroleum-based plastics, can be recovered from organic waste using mixed microbial cultures (MMCs). Research in this field ...has been ongoing for about 25 years and is now in a critical commercialization period. However, few pilot-scale studies are available to analyze its technical feasibility and environmental impact. We ran an MMC PHA production pilot plant for 6 months using local food waste as the feedstock. The traditional three-stage process achieved PHA content of 47.91 ± 1.91% dry cell weight and volumetric productivity of 9.94 ± 0.01 g/L·d, while a novel rapid proliferation stage was built in, the PHA content and productivity could reach 41.39 ± 2.39% cell dry weight and 20.02 ± 0.01 g/L·d, respectively. Life cycle assessment using field data showed that greenhouse warming potential was much more than five times that of the known literature, and the fossil depletion potential was 10.30 (scenario #1)/7.59 (scenario #2) times higher than petroleum-based polyethylene (PE) plastic. However, establishing a resource–energy–water union instead of an isolated plant could achieve environmental benefits compared to PE plastic. This techno-environmental analysis provides emerging MMC PHA producers worldwide with a valuable reference for further development opportunities and market planning.
The design of pH-sensitive supramolecular drug delivery systems for efficient antineoplastic drug delivery remains a huge challenge. Herein, we describe the development of pH-responsive core-shell ...tecto dendrimers (CSTDs) formed using benzimidazole (BM)-modified generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers (G3.NHAc-BM) as a shell and β-cyclodextrin (CD)-modified G5 PAMAM dendrimers (G5.NHAc-CD) as a core. By virtue of the host-guest recognition and pH-responsiveness of BM/β-CD assembly, the pH-sensitive supramolecular CSTDs of G5.NHAc-CD/BM-G3.NHAc were formed and adopted to encapsulate the anticancer drug doxorubicin (DOX) via hydrophobic interactions for pH-responsive drug delivery applications. The synthesis of dendrimer derivatives and the loading of the DOX were well characterized via different methods. We show that the encapsulated DOX can be released in a sustained manner with a rapid release speed under a slightly acidic pH condition (pH < 6), which is similar to acidic tumor microenvironment. The enhanced intracellular release of DOX and improved anticancer activity of the drug-loaded pH-responsive CSTDs were demonstrated and compared with the control CSTDs formed without pH-responsiveness through flow cytometry and viability assays of cancer cells. Furthermore, the pH-sensitive CSTDs also showed efficient drug penetration and growth inhibition of three-dimensional tumor spheroids owing to the faster DOX release in an acidic pH environment. The pH-sensitive G5.NHAc-CD/BM-G3.NHAc CSTDs may be employed as a valuable intelligent delivery system for various anticancer drugs.
The anchoring effect refers to the tendency that an individual's numerical judgment would assimilate to an anchor (a numerical value) that appears before that judgment. This study investigated ...whether the anchoring effect exists in the emotion judgment of younger and older adults and observed the age-related characteristics. This could not only broaden the explanation of the anchoring effect but also link this classic judgment bias with daily emotion judgment to refresh our understanding of older adults' ability in emotional perspective taking.
Participants (older adults: n = 64, age range: 60-74, 27 males; younger adults: n = 68, age range: 18-34, 34 males) read a brief emotional story and compared the protagonist's emotion intensity to a given numerical anchor (lower or higher than the anchor) and then estimated the protagonist's possible emotion intensity in that story. The task was divided into two cases according to anchor relevance (anchors are relevant or irrelevant relative to the judgment target).
The results showed that the estimates were higher under high-anchor than low-anchor conditions, suggesting the robust anchoring effect. Further, the anchoring effect was greater for anchor-relevant than anchor-irrelevant tasks and for negative rather than positive emotions. No age differences were found.
The results indicated that the anchoring effect is robust and stable for younger and older adults, even though the anchor information seemed irrelevant. Finally, perceiving others' negative emotions is a crucial but rather difficult aspect of empathy, which could be a challenge and requires more caution for accurate interpretation.
One way to reduce healthcare costs is to target the high spenders who remain persistently high in cost over time. Using claims data from China between 2010 to 2014, we sought to identify the level of ...concentration in spending and the proportion of spenders whose costs remain high over five years. Using a transition matrix and a linear regression strategy, we find that the top 10% of the spenders account for more than 50% of total expenditures. Of the individuals who were in the top 10% in 2010, 33.6% remained in the top 10% one year later and 23.6% were still in that category even four years later. Past spending plays a major role in the dynamic of health spending. A 10% increase in expenditure is associated with an increase of 0.36% to 1.33% of spending in the future. Persistence has some heterogeneity in terms of age, gender, and income level. Many diseases have strong predictive power for future spending. Research on the concentration and persistence of health expenditures will inform policymakers in terms of controlling costs and providing protection for catastrophic spending.
In this paper, a novel idea of sigma-delta modulator (SDM) is proposed based on our high-order (greater than or equal to 4th order) op-amp sharing technology. The operation timing, adder, integrator ...structure and the switched-capacitor op-amps common-mode negative-feedback of the conventional single-loop cascade-of-integrators with feedforward (CIFF) modulator are improved, so that the nth-order integration function can be accomplished by using one op-amp. Finally, a high-precision and low-power sigma-delta modulator for speech communication is realized. The proposed 4th-order CIFF sigma-delta modulator based on our high-order op-amp sharing is utilized in 0.18 µm standard CMOS process and occupies an area of 0.218 mm2. Simulation results show that the SNDR is 103.91 dB and the ENOB is 16.97 bits with a sampling rate of 2.56 MHz, an oversampling ratio of 256, and signal bandwidth of 5 kHz. Proposed modulator has a supply voltage of 5 V and costs a power consumption of 2.29mW. The power consumption of proposed op-amp sharing idea is 29.67 % less than that of the conventional case.
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