Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study ...aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed.
6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter.
Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 μg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 μg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer's patches (PPs) in rats.
6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.
The rational combinations of low/high-density metallic materials have been proved to be effective in shielding high-energy electron radiation, however, little has been studied and reported about ...their synthesis, microstructure, properties and stability against irradiation. In present work, Mg–Li alloy and pure Ta sheets were used to prepare such a novel low/high-density shielding composite by accumulative roll bonding (ARB). Results showed that a uniformed microstructure of composite could be produced after four ARB cycles. Both ARB process and irradiation caused no obvious change in phase compositions of raw materials. In larger areal mass 8.2–12.3 g/cm2, the Mg–Li/Ta composite is a more efficient shield than pure Mg–Li and Ta. Treated by irradiation, a notable number of cavities accompanied by dislocations were formed as main defects in α-Mg phase. The induced dislocations facilitated the nucleation and growth of {1 0–1 2} twins, which in turn acted as sinks of defects. By contrast, Ta phase exhibited good radiation stability as no signs of visible cavities. During ARB process and irradiation, the textures of α-Mg and Ta in composite all varied distinctly. The average micro-hardness of Mg–Li and Ta phase increased with ARB cycles. Treated by irradiation, Mg–Li matrix was sharply hardened while hardness of Ta was slightly decreased. The tensile strength of Mg–Li/Ta composite increased in ARB process and reached the maximum after four cycles. After irradiation, composite exhibited same strength but severe loss of ductility.
•A novel high-efficiency Mg–Li/Ta composite for shielding of high-energy electron.•Mg–Li/Ta composite was successfully fabricated by accumulative roll bonding (ARB).•Evolution of microstructure, texture and mechanical properties during ARB process.•Irradiation responses on microstructure and mechanical properties of composite.
Xin Y, Zhang W, Mao C, et al. Onco Targets Ther. 2020;13:1833-1844. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of ...the article, concerns were raised about the duplication of images from Figures 4 with images from unrelated articles. Specifically, The images for Figure 4B and 4D have been duplicated with images for Figures 1C, 2E and 6D from Li C, Zhang Y, Tang Y, Xiao J, Gao F, Ouyang Y, Cheng X. LncRNA CRNDE modulates cardiac progenitor cells' proliferation and migration via the miR-181a/LYRM1 axis in hypoxia. J Thorac Dis. 2020;12(5):2614-2624. https://doi.org/10.21037/jtd.2020.03.22. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted".
For studying the stability of wind turbine with direct drive permanent magnet synchronous generator connected to power grid, after suffering a small disturbance and effectively designing the ...controllers' parameters, a complete small signal model of the system is built. By means of eigenvalue analysis, the relation between the modes and state variables can be discovered. Then, the influences of the controllers' parameters on the traces of eigenvalues are analysed, which helps to design controllers' parameters. A simulation model of the system, based on MATLAB/SIMULINK is presented. The simulation results show that the system is stable after suffering small disturbance of a wind velocity step down and a step up, and the system dynamic responses are consistent with the result of small-signal analysis.
Aims
RpoE is quite immunogenic and can be used as a candidate vaccine for Streptococcus suis infection via immunoproteomics as reported in our previous studies. In this study, we aimed to verify the ...immunogenicity of recombinant RpoE and its protective effect against of S. suis.
Methods and Results
The RpoE protein was successfully expressed in Escherichia coli, and the purified recombinant protein was mixed with ISA206 to prepare an S. suis subunit vaccine. Mice were immunized with the RpoE subunit vaccine and then infected with the virulent S. suis strain ZY05719. Subunit vaccine‐immunized mice achieved 50% protection, less pathological damage and less bacterial distribution in each organ compared with the control mice. Furthermore, in vitro culture, showed that mouse antisera significantly (P ＜ 0·001) inhibited the growth of S. suis, and qRT‐PCR results showed that RpoE successfully induced the up‐regulation of IL‐6 and TNF‐α cytokines.
Conclusions
RpoE mice were vaccinated to obtain immune protection, which may be candidates for S. suis subunit vaccine.
Significance and Impact of the Study
The results of this study will provide new ideas for the development of safe and effective recombinant subunits vaccines for S. suis.
Summary
Aims
The aim of this study was to explore the factors associated with the occurrence, subsequent prognoses and need for additional medications following cutaneous adverse drug reactions ...(ADRs) among inpatients.
Methods and measures
This is a case–control study, nested in a large cohort study of 473,446 inpatients hospitalised from 2005 to 2008, examined cutaneous ADRs. A 1 : 5 strategy of individually matching age and principal diagnosis was applied to the data of cases (n = 700) and corresponding controls (n = 3365).The severity of ADRs was evaluated using Naranjo algorithms by senior pharmacists in the medical centre. Medical chart reviews and claim data analyses were analysed to explore risk factors associated with the occurrence and impact of cutaneous ADRs. Economic impacts in terms of length of stay and medical expenses were also analysed.
Results
The number of drug prescriptions and secondary diagnoses, and the department to which the patient was admitted, significantly contributed to the risk of cutaneous ADRs and subsequent prognosis. In addition to physician's seniority, the Naranjo score was also positively associated with patients’ prognosis. Medical expenses associated with cutaneous ADRs patients ($US 916) were more than 2.5‐fold higher than those patients who were not afflicted ($US 318).
Conclusion
The study identified risk factors for cutaneous ADRs in terms of both patient characteristics and drug complexity. The present analyses indicate characteristics and mechanisms of cutaneous ADRs among inpatients, which provide clues for future intervention strategies and management issues in healthcare settings.
Abstract
China is undergoing rapid urbanization, which has caused undesirable urban sprawl and ecological deterioration. Combining information technology for ecological environment governance is an ...effective measure to improve governance efficiency. In this paper, based on the analysis of the ecological restoration and governance case of S Island in Chongqing, an ecological intelligent governance system architecture based on the integration of multiple information technologies such as digital twin is extracted. The research shows that the S Island is based on the technical concept of the digital twin, and integrates a variety of information technology integration, collects and processes a large amount of data generated in the whole process of S Island repair and operation, and builds it based on the digital twin concept and accurately maps the physical space. This system model can be stored and processed based on the integrated data, realize knowledge graph visualization, algorithm optimization, and iterative integration for different objects and application scenarios, and finally serve different functional modules in ecological governance, which can be used to support Smart governance of cities.
We investigated low-hydrogen SiN films prepared by a low temperature (350 degrees C) PECVD method. The impact of SiH(4)/N(2) flow ratio and radio frequency power on the hydrogen content in the SiN ...films was studied. In this work, we demonstrated a low-loss sub-micron SiN waveguide by using the corresponding optimal SiN films. The propagation loss was found to be as low as -2.1+/-0.2 dB/cm at 1550 nm with waveguide cross-section of 700 nm x 400 nm. The results suggest that the SiN films grown by PECVD with low hydrogen can be used in photonics integrated circuits for new generation communications applications.
Abstract The current study used a rat model to investigate the underlying mechanisms of blast-induced tinnitus, hearing loss, and associated traumatic brain injury (TBI). Seven rats were used to ...evaluate behavioral evidence of tinnitus and hearing loss, and TBI using magnetic resonance imaging following a single 10-msec blast at 14 psi or 194 dB sound pressure level (SPL). The results demonstrated that the blast exposure induced early onset of tinnitus and central hearing impairment at a broad frequency range. The induced tinnitus and central hearing impairment tended to shift towards high frequencies over time. Hearing threshold measured with auditory brainstem responses also showed an immediate elevation followed by recovery on day 14, coinciding with behaviorally-measured results. Diffusion tensor magnetic resonance imaging results demonstrated significant damage and compensatory plastic changes to certain auditory brain regions, with the majority of changes occurring in the inferior colliculus and medial geniculate body. No significant microstructural changes found in the corpus callosum indicates that the currently adopted blast exposure mainly exerts effects through the auditory pathways rather than through direct impact onto the brain parenchyma. The results showed that this animal model is appropriate for investigation of the mechanisms underlying blast-induced tinnitus, hearing loss, and related TBI. Continued investigation along these lines will help identify pathology with injury/recovery patterns, aiding development of effective treatment strategies.
Background
There is limited information involving population data about the role of maternal health, fetal growth and neonatal health on children's developmental status at ages 4–7 years. Our aim was ...to determine the contribution of maternal, fetal and neonatal health to developmental status at ages 4–7 years.
Methods
In this 7‐year follow‐up prospective cohort study, a sample of 26 803 mothers participated in the beginning. Among their children, 19 187 voluntarily completed the development screening test or the social life ability survey, which were designed for two different age groups (<6 or ≥6 years old, respectively). Logistic regression analysis was used to link the data with the prenatal outcome card and interview questionnaire applied to pregnant women in previous study, to the analysis of various related factors such as demographic, socio‐economic, disease and menstrual history, marriage and pregnancy care.
Result
Univariate and multivariate logistic regression analysis were used separately in two age groups 4–6 (n = 8439) and 6–7 (n = 10 748) years old to analyse relative factors. Maternal age of 25–30 years, maternal education of high school and greater, family income and not drinking during pregnancy were associated with higher scores in development.
Conclusion
Both preconception and pregnancy health education and health care are the important maternal factors closely associated with children's cognitive and social competence. Public health policies for preconception care and public welfare for high‐quality childcare are essential for improving children's life.
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