Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery.

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

A nitrogen-doped carbon nanosheet composited platinum-cobalt single atom alloy catalyst for effective hydrogen evolution reaction.

An electrocatalyst with ultra-small PtCo single atom alloy species evenly dispersed on nitrogen-doped ultra-thin carbon nanosheets (PtCo SAA/NC) was designed. The introduction of single-atom Pt not only maximizes the atomic utilization efficiency of Pt species, but also synergistically enhances the charge transfer characteristics of Co cluster surfaces, thereby increasing the migration and evolution rate of hydrogen ions. The PtCo SAA/NC catalyst exhibits a Tafel slope of 42 mV dec-1 and a low overpotential of 45 mV at 10 mA cm-2 in 0.5 M H2SO4 solution.

Silver nanoparticles induce endothelial cytotoxicity through ROS-mediated mitochondria-lysosome damage and autophagy perturbation: The protective role of N-acetylcysteine.

Silver nanoparticles (AgNPs) are used increasingly often in the biomedical field, but their potential deleterious effects on the cardiovascular system remain to be elucidated. The primary aim of this study was to evaluate the toxic effects, and the underlying mechanisms of these effects, of AgNPs on human umbilical vein endothelial cells (HUVECs), as well as the protective role of N-acetylcysteine (NAC) against cytotoxicity induced by AgNPs. In this study, we found that exposure to AgNPs affects the morphology and function of endothelial cells which manifests as decreased cell proliferation, migration, and angiogenesis ability. Mechanistically, AgNPs can induce excessive cellular production of reactive oxygen species (ROS), leading to damage to cellular sub-organs such as mitochondria and lysosomes. More importantly, our data suggest that AgNPs causes autophagy defect, inhibits mitophagy, and finally activates the mitochondria-mediated apoptosis signaling pathway and evokes cell death. Interestingly, treatment with ROS scavenger-NAC can effectively suppress AgNP-induced endothelial damage.Our results indicate that ROS-mediated mitochondria-lysosome injury and autophagy dysfunction are potential factors of endothelial toxicity induced by AgNPs. This study may provide new evidence for the cardiovascular toxicity of AgNPs and serve as a reference for the safe use of nanoparticles(NPs) in the future.

Water hydration of polyethylene glycol dimethyl ether.

In this work, GHz and THz complex dielectric spectra of a polyethylene glycol dimethyl ether (2000 g/mol) aqueous solution were studied. The reorientation relaxation of water in this kind of macro-amphiphilic molecule solution can be well described by three Debye models, including under-coordinated water, bulk-like water [water molecules in a tetrahedral hydrogen bond network (bulk water) and bulk water molecules affected by hydrophobic groups], and slow hydrating water (water molecules donating hydrogen bonds to hydrophilic ether groups). The reorientation relaxation timescales of bulk-like water and slow hydration water both show increases with concentration from 9.8 to 26.7 ps and from 46.9 to 100.1 ps, respectively. By estimating the ratios of the dipole moment of slow hydration water to the dipole moment of bulk-like water, we calculated the experimental Kirkwood factors of bulk-like and slow hydrating water. The experimental Kirkwood factor of bulk-like water increased from 3.17 to 3.44 with concentrations, while the experimental Kirkwood factor of slow hydrating water roughly remained constant at 4.13 from concentrations of 15%-60%. The estimated water molecule numbers of three water components around monomers also confirm our sorting for water components.

Nuclear-targeted EGF receptor enhances proliferation and migration of human anaplastic thyroid cancer cells.

INTRODUCTION: Epidermal growth factor (EGF) has various important physiological functions, which it exerts by binding to the epidermal growth factor receptor (EGFR). Reports show that EGF expression is strongly correlated with the occurrence and development of many types of tumour. To date, however, the relationship between EGF/EGFR and the occurrence and development of thyroid carcinoma remains unclear. MATERIAL AND METHODS: In the current study, we investigated this phenomenon using human anaplastic thyroid carcinoma cell lines (SUN-80). RESULTS: The results indicated that EGF triggered the EGFR-mediated intracellular signalling pathway, including signal transducers and activators of transcription 1/3/5 (STAT1/3/5) and protein kinase B (AKT) in a time- and dose-dependent manner. In addition, results from EGF-induced EGFR internalization and co-localization analyses showed that clathrin, Rab5/7, and EEA1 play critical roles in the intracellular trafficking of EGF/EGFR. Interestingly, EGF triggered EGFR translocation into the nucleus, while nuclear-localized EGFR affected cell cycle distribution, thereby significantly promoting the ration of S phase. Overall, these findings indicated that nuclear EGFR exerts biological activity and physiological functions, including changing cell cycle, which in turn promotes proliferation and migration of SUN-80 cells. CONCLUSION: These findings lay a foundation for further explorations seeking to understand the biological effects of the EGF/EGFR system on the occurrence and development of thyroid cancer.

Strategies for guided acoustic wave inspection using mobile robots.

Continuous non-destructive monitoring of large-scale structures is extremely challenging with traditional manual inspections. In this paper, we explore possible strategies that a collection of inspection robots could adopt to address this challenge. We envision the continuous inspection of a plate performed by multiple robots or a single robot that combines measurements from multiple locations. The robots use guided ultrasonic waves to interrogate a localized region for defects such as cracking or corrosion. In the detection stage, the receiver operating characteristic defines a detection zone in which a defect is thought to be present. In the localization stage, further measurements are made to locate the defect within this zone to a certain accuracy. We then address the question of what additional measurements are needed to achieve a given level of performance in the presence of uncertainty in robot locations? We explore this problem with Monte Carlo simulations that reveal the compromise between number of robots and performance in terms of defect location accuracy. In an experimental validation example on an aluminium plate, we show that six measurements arranged in a pentagon with a central measurement point leads to localization errors of similar magnitude to the uncertainty in sensor location.

Hypomethylation of Rnase6 Promoter Enhances Proliferation and Migration of Murine Aortic Vascular Smooth Muscle Cells and Aggravates Atherosclerosis in Mice.

Background: Accumulating evidence has implicated DNA methylation in the progression of atherosclerosis (AS). Rnase6 has been reported to be upregulated in AS development, but the specific regulatory mechanism remains unclear. Material/Methods: Peripheral blood and sclerotic plaque tissues from 25 AS patients were collected to detect Rnase6 expression. Methylation-specific polymerase chain reaction (MSP) was used to detected Rnase6 methylation levels in the peripheral blood of AS patients. Rnase6 expression was knocked down or DNA methyltransferase 1 (DNMT1) was overexpressed in OX-LDL-treated mouse aortic smooth muscle cells (MOVAS), and cell proliferation, migration, ROS content, and inflammatory factor secretion levels were detected. 740 Y-P, a PI3K specific agonist, was introduced to verify the effect of Rnase6 promoter hypomethylation on the PI3K/Akt signaling pathway. We knocked down Rnase6 expression in ApoE-/- mice fed with a high-fat diet to examine Rnase6 promoter methylation levels. Plaque areas and inflammatory factor secretion were examined in AS mice overexpressing DNMT1. Results: Rnase6 expression was upregulated in the peripheral blood and plaque tissues of AS patients, accompanied by decreased methylation levels of the Rnase6 promoter. Interfering with Rnase6 expression or overexpressing DNMT1 in OX-LDL stimulated MOVAS inhibited cell proliferation and migration, decreased ROS content and inflammatory factor secretion, and inhibited PI3K pathway protein expression. Rnase6 expression was decreased in the peripheral blood and plaque tissues of si-Rnase6-injected mice, and Rnase6 promoter methylation was increased. Mice overexpressing DNMT1 showed less plaque areas in the aortic root and lower secretion levels of inflammatory factors. Conclusion: Hypomethylation of the promoter of Rnase6 enhanced the proliferation and migration of OX-LDL treated MOVAS, upregulated ROS content and inflammatory factor secretion levels in the cells, and activated the PI3K/Akt signaling pathway.

Superposition model of mode shapes composed of travelling torsional guided waves excited by multiple circular transducer arrays in pipes.

In pipe inspection using ultrasonic guided wave technique, the current commercial transmitters are designed for the unidirectional guided wave excitation using multiple circular piezoelectric transducers arrays in the axial direction. However, the source with many individual transducer elements in arrays has difficulty in achieving an axisymmetric loading perfectly for defect detection. Therefore, a quasi-axisymmetric wave is formed due to many undesired wave modes are launched instead of a pure axisymmetric wave at a given excitation frequency. In this paper, a realistic superposition model of axial multiple transducer arrays is proposed. The model has many potential applications; one example is investigating the source influence on the generated quasi-axisymmetric wave effect. The analytical model is employed to achieve the predictions for investigating a transmitter's influence for the unidirectional enhancement of torsional T(0,1) guided wave mode excitation in a pipe inspection system composing of three piezoelectric transducer ring arrays. The excitation function with variable power levels among transducers in arrays is also introduced. The predictive results using the analytical model for the distribution of circumferential displacement amplitudes over time are verified using the finite element method and a CLV-3D laser vibrometry measurement on a 219.1-mm-outer-diameter steel pipe without defect. A comparison between calculated and test results has been analysed quantitatively. The respective results are in good agreement. Thus, predictions for the superposed wavefield can be used to analyse the realistic characterisation of the excitation function in axial multiple transducer arrays. Additionally, a sensitivity analysis for part-circumferential crack detection using the quasi-axisymmetric torsional modes generated is also evaluated using finite element modelling.

Supplementation with beta-1,3-glucan improves productivity, immunity and antioxidative status in transition Holstein cows.

Dairy cows undergo dramatic physiological changes during the transition from late pregnancy to early lactation, which make them vulnerable to metabolic stress and immune dysfunction. The objective of this study was to evaluate the effects of a commercial beta-1,3-glucan product (Aleta™, containing 50% beta-1,3-glucan) on productivity, immunity and antioxidative status in transition cows. Fifty-four multiparous Holstein cows received a control diet or a diet supplemented with 5 or 10 g of beta-1,3-glucan per cow per day from 21 days before expected calving to 21 days after parturition. Blood samples were collected at day -21, 1, and 21 relative to calving. Colostrum and milk were collected at day 1 and 21 after calving, respectively. Data showed that supplementation with beta-1,3-glucan had no effect on milk composition, but increased milk production. Beta-1,3-glucan treatment also improved the milk quality, as shown by reduced milk somatic cell count and increased immunoglobulin levels in colostrum. Notably, beta-1,3-glucan markedly reduced serum levels of pro-inflammatory cytokines and C-reactive protein, while elevated serum immunoglobulin levels, indicating its immunity enhancement in transition cows. Moreover, beta-1,3-glucan addition reduced the serum malondialdehyde level and enhanced the activities of serum superoxide dismutase and catalase, which enhanced the antioxidative capacity in transition cows. In summary, supplementation with beta-1,3-glucan improves productivity, immunity and antioxidative status in transition dairy cows.

Effects of beta-1,3-glucan supplementation on concentrations of serum metabolites in transition Holstein cows.

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day -21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDLC), very low density lipoprotein (VLDL), glucose, insulin, ß-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDLC, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows.

Liposomes containing recombinant E protein vaccine against duck Tembusu virus in ducks.

To obtain an effective vaccine candidate against duck Tembusu viral (DTMUV) disease which causes egg-drop and great economical loss in the Chinese duck industry, liposome vaccines containing recombinant E protein were prepared and assessed in this study. The recombinant plasmid (PET28a-E) was constructed and transformed into BL21 (DE3) cells to produce E proteins. The recombinant E proteins were purified and entrapped by liposomes through reverse-phase evaporation. Eighty-four cherry valley ducks were randomly divided into seven groups and inoculated intramuscularly at one- or seven-day-old with liposomes-E protein or Freund's adjuvant-E protein vaccine. Blood samples were collected from the first week to the tenth week for serum antibody, plasma for viremia, as well as oropharyngeal and cloacal swabs for virus shedding analyses after being challenged with a 10(2.4) 50% tissue culture infective dose (TCID50) of duck Tembusu virus. Results showed that serum antibody level of the liposomes vaccine was higher than the Freund's adjuvant vaccine, and inoculating twice was superior to once; furthermore, the viremia and virus shedding tests also proved that the liposomes vaccine can provide complete protection against DTMUV challenge. These results demonstrated that the liposomes-E protein vaccine could be used as a potential candidate vaccine to prevent DTMUV infection in ducks.

Serological survey of canine dirofilariosis in Chongqing, Kunming, Nanchang, Fuzhou, Guangzhou, Shenzhen, and Nanning in Southern China.

The present study conducts a serological survey on the presence of canine dirofilariosis in domestic dogs using an enzyme-linked immunosorbent assay (ELISA) kit. A total of 310 household dogs (166 females and 144 males) in Chongqing, Kunming, Nanchang, Fuzhou, Guangzhou, Shenzhen, and Nanning in Southern China were examined. Of the 310 dogs, 42 (13.5%) were seropositive for dirofilariosis. No statistically significant difference was observed in terms of sex in the seroprevalence of dirofilariosis using the ELISA kit. The positive rates for dirofilariosis were 6.6% in the 0-1-year-old group, 13.8% in the 1-4-year-old group, and 21.6% in the less than 4-year-old group. The statistical analysis revealed that significant differences were observed in the 1-4-year-old group (P=0.037, OR=0.441, 95% CI=0.170-1.144) and less than 4-year-old group (P<0.001, OR=0.256, 95% CI=0.095-0.693). In the regional comparison, the shoreline city Shenzhen (18.8%) had a significantly higher prevalence than urban and mountain areas (P<0.05, OR=0.310, 95% CI=0.066-1.445). In conclusion, Dirofilaria immitis infection in domestic dogs was present in Chongqing, Kunming, Nanchang, Fuzhou, Guangzhou, Shenzhen, and Nanning. Therefore, heartworm treatment and/or chemoprophylaxis for the captured domestic dogs are necessary in these areas. To the best of our knowledge, the present study is the first using serological methods to examine D. immitis infection in domestic dogs in Mainland China in the recent years.