A newly developed based on PEG-PLGA co-delivery nanoparticles for chemo-gene combined therapy to suppress colorectal carcinoma
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•The design for a combination therapy for sorafenib and ...PEDF in a nano-formulation aimed to increase anti-tumor effect on CRC was the first time.•Sora@PEDF-NPs showed better inhibition effect on CRC compared with single loaded nanoparticles in vitro and in vivo.•Sora@PEDF-NPs could decrease the acute toxicity comparing with free Sora on Bal b/c mice.•The PEDF would not increase the toxicity of Sora@PEDF-NPs verified by acute toxicity analysis.
Combination treatment through simultaneous delivery of anticancer drugs and gene with nano-formulation has been demonstrated to be an elegant and efficient approach for colorectal cancer therapy. Recently, sorafenib being studied in combination therapy in colorectal cancer (CRC) attracted attention of researchers. On the basis of our previous study, pigment epithelium-derived factor (PEDF) loaded nanoparticles showed good effect on CRC in vitro and in vivo. Herein, we designed a combination therapy for sorafenib (Sora), a multi-kinase inhibitor and PEDF, a powerful antiangiogenic gene, in a nano-formulation aimed to increase anti-tumor effect on CRC for the first time. Sora and PEDF were simultaneously encapsulated in PEG-PLGA based nanoparticles by a modified double-emulsion solvent evaporation method. The obtained co-encapsulated nanoparticles (Sora@PEDF-NPs) showed high entrapment efficiency of both Sora and PEDF — and exhibited a uniform spherical morphology. The release profiles of Sora and PEDF were in a sustained manner. The most effective tumor growth inhibition in the C26 cells and C26-bearing mice was observed in the Sora@PEDF-NPs in comparison with none-drug nanoparticles, free Sora, mono-drug nanoparticles (Sora-NPs and PEDF-NPs) and the mixture of Sora-NPs and equivalent PEDF-NPs (Mix-NPs). More importantly, Sora@PEDF-NPs showed lower toxicity than free Sora in mice according to the acute toxicity test. The serologic biochemical analysis and mice body weight during therapeutic period revealed that Sora@PEDF-NPs had no obvious toxicity. All the data demonstrated that the simultaneously loaded nanoparticles with multi-kinase inhibitor and anti-angiogenic gene might be one of the most potential formulations in the treatment of colorectal carcinoma in clinic and worthy of further investigation.
Corn-soybean rotation and fertilization are common practices improving soil fertility and crop yield. Their effects on bacterial community have been extensively studied, yet, few comprehensive ...studies about the microbial activity, bacterial community and functional groups in a long-term continuous soybean cropping system after corn insertion and fertilization. The effects of corn insertions (Sm: no corn insertion, CS: 3 cycles of corn-soybean rotations and CCS: 2 cycles of corn-corn-soybean rotations) with two fertilization regimes (No fertilization and NPK) on bacterial community and microbial activity were investigated in a long-term field experiment. The bacterial communities among treatments were evaluated using high-throughput sequencing then bacterial functions were predicted based on the FaProTax database. Soil respiration and extracellular enzyme activities were used to assess soil microbial activity. Soil bacterial community structure was significantly altered by corn insertions (
< 0.01) and fertilization (
< 0.01), whereas bacterial functional structure was only affected by corn insertion (
< 0.01). The activities of four enzymes (invertase, β-glucosidase, β-xylosidase, and β-D-1,4-cellobiohydrolase) involved in soil C cycling were enhanced by NPK fertilizer, and were also enhanced by corn insertions except for the invertase and β-xylosidase under NPK fertilization. NPK fertilizer significantly improved soil microbial activity except for soil metabolic quotient (qCO
) and the microbial quotient under corn insertions. Corn insertions also significantly improved soil microbial activity except for the ratio of soil induced respiration (SIR) to basal respiration (BR) under fertilization and the qCO
was decreased by corn insertions. These activity parameters were highly correlated with the soil functional capability of aromatic compound degradation, which was the main predictors of bacterial functional structure. In general, the combination of soil microbial activity, bacterial community and corresponding functional analysis provided comprehensive insights into compositional and functional adaptations to corn insertions and fertilization.
As one of the key technologies of intelligent transportation systems, vehicle re-identification (Re-ID) aims to retrieve the same vehicle from different monitoring scenes and plays an important role ...in building a safe and smart city. With the continuous development of computer vision, the Re-ID method of using supervised learning suffers from the problems of strong reliance on manual annotation in the training process and weak scene generalization ability, so unsupervised learning of vehicle Re-ID gradually becomes the focus of research in recent years. Firstly, the present mainstream vehicle Re-ID datasets and the commonly used model evaluation metrics are introduced. Then, latest unsupervised learning-based vehicle Re-ID methods are grouped into two categories: gene-rative adversarial networks and clustering algorithms according to the current research ideas. Starting from the problems of domain deviation, cross-view deviation and insufficient information of data samples, the former is further divided into
Co-contamination of arsenic and fluoride is widely distributed in groundwater. However, little is known about the interactively influence of arsenic and fluoride, especially the combined mechanism in ...cardiotoxicity. Cellular and animal models exposure to arsenic and fluoride were established to assess the oxidative stress and autophagy mechanism of cardiotoxic damage using the factorial design, a widely used statistical method for assessing two factor interventions. In vivo, combined exposure to high arsenic (50 mg/L) and high fluoride (100 mg/L) induced myocardial injury. The damage is accompanied by accumulation of myocardial enzyme, mitochondrial disorder, and excessive oxidative stress. Further experiment identified that arsenic and fluoride induced the accumulation of autophagosome and increased expression level of autophagy related genes during the cardiotoxicity process. These findings were further demonstrated through the in vitro model of arsenic and fluoride-treated the H9c2 cells. Additionally, combined of arsenic-fluoride exposure possesses the interactively influence on oxidative stress and autophagy, contributing to the myocardial cell toxicity. In conclusion, our data suggest that oxidative stress and autophagy are involved in the process of cardiotoxic injury, and that these indicators showed interaction effect in response to the combined exposure of arsenic and fluoride.
•Arsenic and fluoride change mitochondrial ultrastructure in myocardium.•Arsenic and fluoride induce myocardial oxidative stress and autophagy.•There is interactive effect of arsenic and fluoride on myocardial injury.
Health related quality of life (HRQL) is a research topic that has attracted increasing interests around the world over the past two decades. The 36-item Short Form (SF-36) is a commonly used ...instrument for measuring HRQL. However, the information on Chinese adults' quality of life is limited. This paper reports on the feasibility of using the Mandarin version of SF-36 to evaluate HRQL in the population of Shanghai, China.
A total of 1034 subjects were randomly sampled using a stratified multiple-stage sampling method in Shanghai. Demographic information was collected, and SF-36 was used to measure HRQL.
Internal reliability coefficients were greater than 0.7 in six of the eight SF-36 dimensions, except social function and mental health. Intraclass correlation coefficients ranged from 0.689 to 0.972. Split-half reliability coefficients were higher than 0.9 in five SF-36 dimensions. Validity was assessed by factor analysis and correlation analysis. Our results were basically in accordance with the theoretical construction of SF-36. The average scores of most SF-36 dimensions were higher than 80. The primary influencing risk factors of HRQL included chronic diseases, age, frequency of activities, and geographical region, which were identified using multivariate stepwise regression.
Overall, HRQL in the population of Shanghai is quite good. The Mandarin version of SF-36 is a valid and reliable tool for assessing HRQL.
NiO nanoparticles with average particle size of 25 nm were successfully prepared by anodic arc plasma method. The composition, morphology, crystal microstructure, specific surface area, infrared ...spectra, and particle size distribution of product were analyzed by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and the corresponding selected area electron diffraction (SAED), Fourier transform infrared (FTIR) spectrum, and Brunauer-Emmett-Teller (BET) N2 adsorption. The experiment results show that the NiO nanoparticles are bcc structure with spherical shape and well dispersed, the particle size distribution ranging from 15 to 45 nm with the average particle size is about 25 nm, and the specific surface area is 33 m2/g. The infrared absorption band of NiO nanoparticles shows blue shifts compared with that of bulk NiO.
With the continuous development of industry, an increasing number of nanomaterials are widely used. CdTe-QDs is a nanomaterial with good optical properties, but its release into the natural ...environment may pose a potential threat. The toxicity of nanoparticles in plants is beginning to be questioned, and the effect on phytotoxicity is unclear. In this study, we simulated air pollution and soil pollution (CdTe-QDs concentrations of 0, 0.2, 0.4, 0.8 mmol/L) by spraying and watering the seedlings, respectively. We determined the transport pathways of CdTe-QDs in
and their effects on plant reproductive growth. Spraying CdTe-QDs concentration >0.4 mmol/L significantly inhibited the formation of fruit and decreased the number of seeds. Observation with a laser confocal scanning microscope revealed that CdTe-QDs were mainly transported in plants through the vascular bundle, and spraying increased their accumulation in the anthers and ovaries. The expression level of genes associated with Cd stress was analyzed through RT-qPCR. CdTe-QDs significantly increased the expression levels of 10 oxidative stress-related genes and significantly decreased the expression levels of four cell-proliferation-related genes. Our results reveal for the first time the transport of CdTe-QDs in
flowers and demonstrate that QDs can cause abnormal pollen morphology, form defects of pollen vitality, and inhibit pollen tube growth in
through oxidative damage. These phenomena ultimately lead to the inability of
to complete the normal fertilization process and affect the reproductive growth of the plant.
Freestanding NiO nanowall array is prepared via a hydrothermal synthesis method and shows noticeable Li battery performance with good cycle life and high capacity. Display omitted
► NiO nanowall ...array is prepared by a hydrothermal synthesis method. ► NiO nanowall array with high capacity as anode material for Li ion battery. ► Nanowall array structure is favorable for fast ion/electron transfer.
We report a self-supported NiO nanowall array prepared by a facile hydrothermal synthesis method. The microstructure and morphology of the sample are characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The hydrothermal-synthesized NiO nanowalls with thicknesses of ∼20nm arrange vertically to the substrate forming a net-like nanowall array structure. As anode material for lithium ion batteries, the NiO nanowall array exhibits better electrochemical performances with higher coulombic efficiency and better cycling performance as compared to the dense NiO film. The NiO nanowall array shows an initial coulombic efficiency of 76%, as well as good cycling stability with a capacity of 567mAhg−1 at 0.3Ag−1 after 50 cycles, higher than those of the dense polycrystalline NiO film (361mAhg−1). The superior electrochemical performance is mainly due to the unique nanowall array structure with shorter diffusion length for mass and charge transport.
Severe acute respiratory syndrome coronavirus 2 will coexist with humans for a long time, and it is therefore important to develop effective treatments for coronavirus disease 2019 (COVID-19). Recent ...studies have demonstrated that antiviral therapy is a key factor in preventing patients from progressing to severe disease, even death. Effective and affordable antiviral medications are essential for disease treatment and are urgently needed. Azvudine, a nucleoside analogue, is a potential low-cost candidate with few drug interactions. However, validation of high-quality clinical studies is still limited.
This is a multicentre, randomized, double-blind, placebo-controlled phase III clinical trial involving 1096 adult patients with mild-to-moderate symptoms of COVID-19 who are at high risk for progression to severe COVID-19. Patients will be randomized to (1) receive azvudine tablets 5 mg daily for a maximum of 7 days or (2) receive placebo five tablets daily. All participants will be permitted to use a standard treatment strategy except antiviral therapy beyond the investigational medications. The primary outcome will be the ratio of COVID-19-related critical illness and all-cause mortality among the two groups within 28 days.
The purpose of this clinical trial is to determine whether azvudine can prevent patients at risk of severe disease from progressing to critical illness and death, and the results will identify whether azvudine is an effective and affordable antiviral treatment option for COVID-19.
ClinicalTrials.gov NCT05689034. Registered on 18 January 2023.
•Fluoride adversely affected the ultrastructure of microtubules in mouse hippocampus.•Excessive fluoride reduced the gene and protein expressions of Tubα1a and Tubβ2a in hippocampus.•Fluoride could ...threaten the stability of microtubule by affecting the expression of tubulin dimers.
Axonal and dendrictic degenerations were observed in non-skeleton fluorosis as the neurological manifestations. Microtubules, composed of the assembled tubulin dimers, are the essential cytoskeleton of axon and dendron. However, the effect of fluoride (F) on microtubules status and tubulin dimer expression in central nerves system remains largely unknown. In this study, the ultrastructure of microtubules and expression of Tubα1a and Tubβ2a were detected in hippocampus of mice orally administrated with 25, 50, or 100mgL−1 NaF for 60d. Results showed that in F treatment groups, microtubules were broken into discrete fragments and bended, which were no longer stretched and went along the axon well. In addition, the expression of Tubα1a and Tubβ2a on both gene and protein levels were significantly reduced in high F group. The visual results of immunocytochemistry also confirmed the decreased protein expressions of Tubα1a and Tubβ2a. These findings suggested that microtubule lesions could be an important cause for neurodegeneration observed in fluorosis, and F may threaten the microtubule stability by affecting the expression of tubulin dimers.
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