Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery ...vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body’s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.
Groundwater is critical for the sustainable development of the Loess Plateau, while groundwater quality is generally poor in this area due to natural factors and anthropogenic pollution. This study ...was carried out to investigate the suitability of groundwater for domestic and agricultural purposes in Yan’an City on the Chinese Loess Plateau and to assess its implications to sustainable groundwater management on the plateau. The index levels were compared with the threshold values established by the national and the WHO drinking water guidelines, and the suitability of groundwater for irrigation purposes was assessed using multiple agricultural water quality indicators. An entropy-weighted Technique for Order Preference by Similarity to an Ideal Solution (entropy-weighted TOPSIS) was adopted for overall groundwater quality assessment. The results indicate that the study area is characterized by saline, hard, and slightly alkaline groundwater, mainly of the HCO
3
–Ca·Mg type, accompanied by some minor SO
4
·Cl–Ca·Mg type. The dissolution of carbonates and gypsum and the leaching of soluble salts are important natural processes influencing the groundwater ion chemistry. The parameters TH, TDS, and SO
4
2−
are major indices, while Fe, Mn, F
−
, and NH
4
+
are minor contaminants affecting groundwater quality. The overall groundwater quality is generally acceptable for irrigation, and most of the water is suitable for drinking. Rainwater harvesting, water quality improvement programs, regular water quality monitoring, and multidisciplinary water research programs are suggested as measures for sustainable groundwater management on the Loess Plateau.
A disposable electrochemical sensor based on silver nanoparticle-embedded cellulose hydrogel composites was developed for sensitive detection of sulfamethoxazole residues in meat samples. Scanning ...electron microscopy confirmed the porous structure of the cellulose matrix anchored with 20-50 nm silver nanoparticles (AgNPs). Fourier transform infrared spectroscopy and X-ray diffraction verified that the metallic AgNPs coordinated with the amorphous cellulose chains. At an optimum 0.5% loading, the nanocomposite sensor showed a peak-to-peak separation of 150 mV, diffusion-controlled charge transfer kinetics, and an electron transfer coefficient of 0.6 using a ferro/ferricyanide redox probe. Square-wave voltammetry was applied for sensing sulfamethoxazole based on its two-electron oxidation peak at 0.72 V vs. Ag/AgCl in Britton-Robinson buffer of pH 7.0. A linear detection range of 0.1-100 μM sulfamethoxazole was obtained with a sensitivity of 0.752 μA/μM and limit of detection of 0.04 μM. Successful recovery between 86 and 92% and less than 6% RSD was achieved from spiked meat samples. The key benefits of the proposed disposable sensor include facile fabrication, an antifouling surface, and a reliable quantification ability, meeting regulatory limits. This research demonstrates the potential of novel cellulose-silver nanocomposite materials towards developing rapid, low-cost electroanalytical devices for decentralized on-site screening of veterinary drug residues to ensure food safety.
The modular multilevel converter is one of the most attractive converter topologies for high-voltage dc transmission systems, but it needs at least 10 min during the system uncontrolled precharge ...stage to verify the stability and reliability of submodules (SMs), making the capacitor static voltage balancing a key issue. This paper proposes a novel method based on self-power supply control for balancing capacitor static voltage. Because of the influence of self-power supplies on capacitor voltages, the method can keep the capacitor static voltage balanced by controlling the input characteristic of SMs self-power supplies. The control signals of self-power supplies have a fixed frequency and duty ratio, and they can be determined based on capacitor voltage sorting results and self-power supply output support capacitor. Compared with previous works, this method has less computation, and it does not rely on IGBTs and additional complex circuits except for the self-power supplies. This can save on the software and hardware costs. The proposed method also leads to improved equalizing resistances and reduced active power losses of the SMs. Simulations and experimental studies were conducted, and the results confirm the effectiveness of the proposed method.
Due to various human activities, soil quality under different land use patterns is deteriorating all over the world. This deterioration is very complex in the river irrigation area and is caused by ...multi-point and non-point source pollution and seasonal variation. Therefore, the characteristics and sources of soil metal pollution in river irrigation area of Baoji city were analyzed. The contents of 8 metals were given by ICP-MS, in the soil samples. Statistical methods, geo-accumulation index (I.sub.geo) and potential ecological risk index (RI) were conducted to evaluate the spatial distribution features, sources and ecological risks of metal contamination from the study area soil. Principal component analysis and cluster analysis were used to analyze the pollution sources of metal. The analysis showed that Cd is the most polluted, and human activities represented a great impact on the contents of Zn, Ni, Cu and Cd in soil, Cd post moderate-strong pollution and strong risk, Cd has a maximum Igeo value of 3.17. All rivers were at risk of moderate pollution levels in study. Among them, some rivers had even reached strong pollution level. Pollution caused by human activities was the most significant pollution source of metal in the research area soil.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The clinical efficacy for treating of celastrol rheumatoid arthritis (RA) has been well-documented, but its mechanism of action remains unclear. Here we explored through what proteins and processes ...celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. In this paper, expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Network pharmacology uses bioinformatics to broaden our understanding of drug actions and thereby advance drug discovery. Here we apply network pharmacology to generate testable hypotheses about the ...multi-target mechanism of celastrol against systemic lupus erythematosus (SLE).
We reconstructed drug–target pathways and networks to predict the likely protein targets of celastrol and the main interactions between those targets and the drug. Then we validated our predictions of candidate targets by performing docking studies with celastrol.
The results suggest that celastrol acts against SLE by regulating the function of several signaling proteins, such as interleukin 10, tumor necrosis factor, and matrix metalloprotein 9, which regulate signaling pathways involving mitogen-activated protein kinase and tumor necrosis factor as well as apoptosis pathways. Celastrol is predicted to affect networks involved mainly in cytokine activity, cytokine receptor binding, receptor ligand activity, receptor regulator activity, and cofactor binding. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of interaction.
This network pharmacology strategy may be useful for discovery of multi-target drugs against complex diseases, specifically, it provides protein targets associated with SLE that may be further tested for therapeutic potential by celastrol.
The soil-water characteristic curve (SWCC) is an essential tool to determine hydraulic and mechanical properties of unsaturated soils. As an inherent influencing factor, soil texture controls the ...characteristics of SWCCs. Fractal theory can quantitatively describe the physical characteristics of soil. This study used particle size distribution data and water content data contained in the UNSODA2.0 database to explore the fractal characteristics of 12 soil types with different textures under different matrix suctions. The SWCC fractal model was adopted to characterize the hydraulic properties of soil with various soil textures. The findings revealed that the mass fractal dimensions of particles from these 12 different soil types significantly differed and were closely related to the clay content. Fractal dimension increased with increasing clay content. The fractal dimension established a good relationship between soil structure and hydraulic properties. Fractal analysis can be used to determine the connection between physical properties and soil hydraulic parameters. The estimated results of the SWCC fractal model indicated that it had a good performance regarding the description of SWCCs for the 12 soil textures. The soil structure could be described through fractal dimensions, which can effectively indicate soil hydraulic characteristics. The estimated fractal dimension of this model could be obtained by particle size distribution. Furthermore, using the SWCC fractal model, we found that the SWCC of coarse textured soil changed sharply in the low suction stage and its residual water content was small, and the SWCC of fine textured soil changed gently with a large residual water content. The water retention capacity followed the order clay > silty clay > sandy clay > clay loam > silty clay loam > sandy clay loam > loam > silt loam > sandy loam > silt > loamy sand > sand.
Abstract
Background
Adolescent idiopathic scoliosis (AIS) is characterized by low lean mass without vertebral deformity. The cause-and-effect relationship between scoliosis and paraspinal muscle ...imbalance has long puzzled researchers. Although
FTO
has been identified as a susceptibility gene for AIS, its potential role in the asymmetry of paraspinal muscles has not been fully elucidated.
Methods
We investigated the role of
Fto
in murine myoblast proliferation, migration, and myogenic differentiation. We examined its precise regulatory influence on murine muscle fiber remodeling in vitro and in vivo. We identified the downstream target gene of
Fto
by screening key regulators of murine muscle fiber remodeling and identified its m
6
A reader. Deep paraspinal muscle samples were obtained from the concave and convex sides of AIS patients with or without Schroth exercises, and congenital scoliosis served as a control group. We compared the content of type I fibers, expression patterns of fast- and slow-type genes, and levels of FTO expression.
Results
FTO contributed to maintain the formation of murine slow-twitch fibers both in vitro and in vivo. These effects were mediated by the demethylation activity of FTO, which specifically demethylated NFATC1 and prevented YTHDF2 from degrading it. We found a significant reduction in type I fibers, mRNA levels of
MYH7
and
MYH7B
, and expression of FTO on the concave side of AIS. The percentage of type I fibers showed a positive correlation with the expression level of
FTO
. The asymmetric patterns observed in AIS were consistent with those seen in congenital scoliosis, and the asymmetry of FTO expression and fiber type in AIS was largely restored by Schroth exercises.
Conclusions
FTO supports the formation of murine slow-twitch fibers in an NFATC1–YTHDF2 dependent manner. The consistent paraspinal muscle features seen in AIS and congenital scoliosis, as well as the reversible pattern of muscle fibers and expression of FTO in AIS suggest that
FTO
may contribute to the muscle fiber remodeling secondary to scoliosis.
Bloch oscillations (BOs) were initially predicted for electrons in a solid lattice to which a static electric field is applied. The observation of BOs in solids remains challenging due to the ...collision scattering and barrier tunnelling of electrons. Nevertheless, analogies of electron BOs for photons, acoustic phonons and cold atoms have been experimentally demonstrated in various lattice systems. Recently, BOs in the frequency dimension have been proposed and studied by using an optical micro-resonator, which provides a unique approach to controlling the light frequency. However, the finite resonator lifetime and intrinsic loss hinder the effect from being observed practically. Here, we experimentally demonstrate BOs in a synthetic frequency lattice by employing a fibre-loop circuit with detuned phase modulation. We show that a detuning between the modulation period and the fibre-loop roundtrip time acts as an effective vector potential and hence a constant effective force that can yield BOs in the modulation-induced frequency lattices. With a dispersive Fourier transformation, the pulse spectrum can be mapped into the time dimension, and its transient evolution can be precisely measured. This study offers a promising approach to realising BOs in synthetic dimensions and may find applications in frequency manipulations in optical fibre communication systems.
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