Aggregation‐caused fluorescence quenching with insufficient production of reactive oxygen species (ROS) has limited the application of photosensitizers (PSs) in fluorescence‐imaging‐guided ...photodynamic therapy (PDT). Aggregation‐induced emission PSs (AIE‐PSs) exhibit enhanced fluorescence intensity and a high efficiency of ROS generation in the aggregation state, which provides an opportunity to solve the above problems. Herein, a series of AIE‐PSs are successfully designed and synthesized by adjusting the D–A intensity through molecular engineering. The photophysical properties and theoretical calculations prove that the synergistic effect of 3,4‐ethylenedioxythiophene and quinolinium increases the intramolecular charge transfer effect (ICT) of the whole molecule and promotes the intersystem crossing (ISC) from the lowest excited singlet state (S1) to the lowest triplet state (T1). Among these AIE‐PSs, the optimal AIE‐PS (TPA‐DT‐Qy) exhibits the highest generation yield of 1O2 (5.3‐fold of Rose Bengal). Further PDT experiments show that the TPA‐DT‐Qy has a highly efficient photodynamic ablation of breast cancer cells (MCF‐7 and MDA‐MB‐231) under white light irradiation. Moreover, the photodynamic antibacterial study indicates that TPA‐DT‐Qy has the discrimination and excellent photodynamic inactivation of S. aureus. This work provides a feasible strategy for the molecular engineering of novel AIE‐PSs to improve the development of fluorescence‐imaging‐guided PDT.
A series of aggregation‐induced emission‐photosensitizers (AIE‐PSs) are designed and synthesized successfully to achieve photosensitizers with excellent properties containing AIE‐active, high 1O2 generation, NIR emission, mitochondrial targeting. The introductions of triphenylamine, 3,4‐ethylenedioxythiophene, and quinolinium blocks do these AIE‐PSs work, which are appropriate for fluorescence‐imaging‐guided photodynamic therapy. Typically, TPA‐DT‐Qy exhibits efficient photodynamic anticancer and antibacterial.
The ability to accurately identify and isolate cells is the cornerstone of precise disease diagnosis and therapies. A single-step cell identification method based on logic analysis of multiple ...surface markers will have unique advantages because of its accuracy and efficacy. Herein, using multiple DNA aptamers for cancer biomarker recognition and associative toehold activation for signal integration and amplification as two molecular keys, we have successfully operated a cell-surface device that can perform AND Boolean logic analysis of multiple biomarkers and precisely label the target cell subtype in large populations of similar cells via the presence or absence of different biomarkers. Our approach can achieve single-step cancer cell identification and isolation with excellent sensitivity and accuracy and thus will have broad applications in biological science, biomedical engineering, and personalized medicine.
Rivets are usually used to connect the skin of an aircraft with joints such as frames and stringers, so the skin of the connection part is a porous structure. During the service of the aircraft, ...cracks appear in some difficult-to-detect parts of the skin porous structure, which causes great difficulties in the service life prediction and health monitoring of the aircraft. In this paper, a secondary development subroutine in PYTHON based on ABAQUS-XFEM is compiled to analyze the cracks that are difficult to monitor in the porous structure of aircraft skin joints. The program can automatically analyze the stress intensity factor of the crack tip with different lengths in the porous structure, and then the residual fatigue life can be deduced. For the sake of safety, the program adopts a more conservative algorithm. In comparison with the physical fatigue test results, the fatigue life of the simulation results is 16% smaller. This project provides a feasible simulation method for fatigue life prediction of porous structures. It lays a foundation for the subsequent establishment of digital twins for damage monitoring of aircraft porous structures.
Genetic switching driven by noise is a fundamental cellular process in genetic regulatory networks. Quantitatively characterizing this switching and its fluctuation properties is a key problem in ...computational biology. With an autoregulatory dimer model as a specific example, we design a general methodology to quantitatively understand the metastability of gene regulatory system perturbed by intrinsic noise. Based on the large deviation theory, we develop new analytical techniques to describe and calculate the optimal transition paths between the on and off states. We also construct the global quasi-potential energy landscape for the dimer model. From the obtained quasi-potential, we can extract quantitative results such as the stationary distributions of mRNA, protein and dimer, the noise strength of the expression state, and the mean switching time starting from either stable state. In the final stage, we apply this procedure to a transcriptional cascades model. Our results suggest that the quasi-potential energy landscape and the proposed methodology are general to understand the metastability in other biological systems with intrinsic noise.
Titanium alloys are extensively used in the manufacturing of key components in aerospace engines and aircraft structures due to their excellent properties. However, aircraft skins in harsh operating ...environments are subjected to long-term corrosion and pressure concentrations, which can lead to the formation of cracks and other defects. In this paper, a detection probe is designed based on the principle of alternating current field measurement, which can effectively detect both surface and buried defects in thin-walled titanium alloy plates. A finite element simulation model of alternating current field measurement detection for buried defects in thin-walled TC4 titanium alloy plates is established using COMSOL 5.6 software. The influence of defect length, depth, and excitation frequency on the characteristic signals is investigated, and the detection probe is optimized. Simulation and experimental results demonstrate that the proposed detection probe exhibits high detection sensitivity to varying lengths and depths of buried defects, and can detect small cracks with a length of 3 mm and a burial depth of 2 mm, as well as deep defects with a length of 10 mm and a burial depth of 4 mm. The feasibility of this probe for detecting buried defects in titanium alloy aircraft skin is confirmed.
To improve the thermal stability of the cellulose insulation paper used in power transformers, Al 2 O 3 nanoparticles were used to modify traditional cellulose insulation paper. Molecular simulations ...and experimental methods were used to analyze the enhancement and the microscopic mechanism of Al 2 O 3 nanoparticles in the thermal aging process of insulation paper. Molecular simulations were performed for an unmodified and a Al 2 O 3 nanoparticle-modified cellulose model to explore the changes in mechanical properties, cohesive energy densities and the glass transition temperatures of the two models in a temperature range of 70-150 °C. The results of these simulations showed that the elastic modulus of the cellulose model modified with Al 2 O 3 nanoparticles was larger than that of the unmodified model. Further, the addition of Al 2 O 3 nanoparticles increased the glass transition temperature, signifying that the number of hydrogen bond connections was increased and the thermal stability of the modified model was improved. In addition, physical samples of modified insulation papers mixed with Al 2 O 3 nanoparticles were made, and accelerated thermal aging experiments on these samples showed that the decrease in the degree of polymerization for the modified insulation paper was slower than that of the unmodified insulation paper. Further, breakdown tests suggested that the addition of Al 2 O 3 nanoparticles has a certain positive effect on the AC breakdown voltage. Both the simulated and experimental results indicate that the addition of Al 2 O 3 nanoparticles improves the thermal aging performance of cellulose insulation paper.
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•EBSD misorentation analysis is developed to depict localized creep-fatigue damage.•GND density map is explored to understand creep-fatigue failure physical ...mechanism.•Semi-quantitative study of EBSD parameters supports microscopic damage degree.
A large number of strain-controlled creep-fatigue tests under wide loading waveforms are conducted at 650 ℃ in nickel-based forged GH4169 superalloy. Comprehensive characterizations, including scanning electron microscope (SEM), electron backscatter diffraction (EBSD) and transmission electron microscope (TEM), are observed from the post-test examinations. Particular focus is brought to the physical understanding of damage mechanisms under wide creep-fatigue loading conditions using EBSD analysis. The representative misorientation parameters are calculated for constructing diffraction-based misorientation mapping. Semi-quantitative analysis of longitudinal EBSD observations is conducted to prove that strain ratio has little influence on creep-fatigue damage degrees, while dwell time causes noticeable changes to damage progressions. In particular for geometrically necessary dislocation (GND) map explored in this work, more fundamental information based on failure physics is obtained to analyze the creep-fatigue crack initiation mechanism.
The polycyclic aromatic hydrocarbon (PAH)-degrading strain Q8 was isolated from oilfield produced water. According to the analysis of a biochemical test, 16S rRNA gene, house-keeping genes and ...DNA-DNA hybridization, strain Q8 was assigned to a novel species of the genus
. The strain could not only grow in mineral salt medium (MM) and utilize naphthalene and pyrene as its sole carbon source, but also degraded mixed naphthalene, phenanthrene, anthracene and pyrene. The degradation ratio of these four PAHs reached 100%, 95.4%, 73.8% and 53.4% respectively after being degraded by Q8 for seven days. A comparative experiment found that the PAHs degradation efficiency of Q8 is higher than that of
and
, which have the capacities to remove PAHs. Fourier transform infrared spectra, saturate, aromatic, resin and asphaltene (SARA) and gas chromatography-mass spectrometry (GC-MS) analysis of crude oil degraded by Q8 were also studied. The results showed that Q8 could utilize
-alkanes and PAHs in crude oil. The relative proportions of the naphthalene series, phenanthrene series, thiophene series, fluorene series, chrysene series, C21-triaromatic steroid, pyrene, and benz(a)pyrene were reduced after being degraded by Q8.
sp. nov. Q8 had the capacity to remediate water and soil environments contaminated by PAHs or crude oil, and provided a feasible way for the bioremediation of PAHs and oil pollution.
What is the specific mechanism of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exos) in regulating endometrial repair and regeneration?
In this study, UCMSC-exos were harvested by ...differential ultracentrifugation from umbilical cord mesenchymal stem cell culture supernatant and identified with western blotting, transmission electron microscopy and nanoparticle tracking analysis. Transforming growth factor-β1 (TGFβ1) at different concentrations was used to construct the intrauterine adhesions cell model. The fibrotic markers were assessed by quantitative reverse transcription-polymerase chain reaction and western blotting. The effects of miR-145-5p over-expression on endometrial fibrosis were assessed. Dual luciferase assay was performed to verify the relationship between miR-145-5p and zinc finger E-box binding homeobox 2 (ZEB2).
The isolated UCMSC-exos had a typical cup-shaped morphology, expressed the specific exosomal markers Alix, CD63 and TSG101, and were approximately 50–150 nm in diameter. TGFβ1 at 10 ng/ml significantly promoted endometrial fibrosis, which was reversed by 20 µg/ml UCMSC-exos. Exosomal miR-145-5p ameliorated TGFβ1-induced endometrial fibrosis. ZEB2 was inversely regulated by exosomal miR-145-5p as a direct target.
UCMSC-exos might reverse endometrial stromal cell fibrosis by regulating the miR-145-5p/ZEB2 axis, representing a potential novel strategy to promote endometrial repair.
ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 ...epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.
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