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"Li, Xiong"
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Activation of AMPK by simvastatin inhibited breast tumor angiogenesis via impeding HIF‐1α‐induced pro‐angiogenic factor
Substantial data from preclinical studies have revealed the biphasic effects of statins on cardiovascular angiogenesis. Although some have reported the anti‐angiogenic potential of statins in malignant tumors, the underlying mechanism remains poorly understood. The aim of this study is to elucidate the mechanism by which simvastatin, a member of the statin family, inhibits tumor angiogenesis. Simvastatin significantly suppressed tumor cell‐conditioned medium‐induced angiogenic promotion in vitro, and resulted in dose‐dependent anti‐angiogenesis in vivo. Further genetic silencing of hypoxia‐inducible factor‐1α (HIF‐1α) reduced vascular endothelial growth factor and fibroblast growth factor‐2 expressions in 4T1 cells and correspondingly ameliorated HUVEC proliferation facilitated by tumor cell‐conditioned medium. Additionally, simvastatin induced angiogenic inhibition through a mechanism of post‐transcriptional downregulation of HIF‐1α by increasing the phosphorylation level of AMP kinase. These results were further validated by the fact that 5‐aminoimidazole‐4‐carboxamide ribonucleotide reduced HIF‐1α protein levels and ameliorated the angiogenic ability of endothelial cells in vitro and in vivo. Critically, inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin‐induced anti‐angiogenesis, which was accompanied by the reduction of protein levels of HIF‐1α and its downstream pro‐angiogenic factors. These findings reveal the mechanism by which simvastatin induces tumor anti‐angiogenesis, and therefore identifies the target that explains the beneficial effects of statins on malignant tumors. Simvastatin significantly suppressed tumor angiogenesis promoted by HIF‐1α‐induced pro‐angiogenic factors in 4T1 tumor cells. Further inhibition of AMPK phosphorylation by compound C almost completely abrogated simvastatin‐induced anti‐angiogenesis, which was accompanied by the reduction of protein levels of HIF‐1α and its downstream pro‐angiogenic factors.
Journal Article
Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma
Background
Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.
Methods
A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca
2+
image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.
Results
We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.
Conclusions
These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
Journal Article
Theoretical Investigation on Molecular Properties of Baicalein (C15H10O5), the Major Component of Traditional Chinese Medicine Scutellaria Baicalensis Georgi
Baicalein (5,6,7-trihydroxyflavone: C
15
H
10
O
5
, a typical flavonoid), the predominated component of Scutellaria baicalensis Georgi (a traditional Chinese medicine, i.e., Huang Qin), has been simulating great interests due to its various promising and advantage. Numerous molecular properties can be theoretically investigated by quantum chemistry calculation based on the density functional theory, producing stable and reliable results comparable to the case through experimental method. In this work, we systematically studied the molecular properties of baicalein by performing the analyses (geometry, infrared spectrum, bond order, molecular orbital, density of states, localized molecular orbital, localized orbital locator, electron localization function, π-electron population, aromaticity, electrostatic potential, atomic charge, etc.) based on the theoretical quantum chemistry computation with the setup of B3LYP/def2-TZVP. No doubt, our work will provide assistance and theoretical guidance for further research on the component from the traditional Chinese medicine, such as the baicalein involved in this paper, in the future.
Journal Article
Enzyme-mediated nitric oxide production in vasoactive erythrocyte membrane-enclosed coacervate protocells
The design and construction of synthetic therapeutic protocells capable of establishing cognate chemical communication channels with living cells is an important challenge for synthetic biology and bio-engineering. Here we develop a step towards protocell-mediated nitric-oxide-induced vasodilation by constructing a new synthetic cell model based on bio-derived coacervate vesicles with high haemocompatibility and increased blood circulation times. The hybrid protocells are prepared by the spontaneous self-assembly of haemoglobin-containing erythrocyte membrane fragments on the surface of preformed polysaccharide–polynucleotide coacervate micro-droplets containing glucose oxidase. We use the sequestered enzymes to program a spatially coupled glucose oxidase/haemoglobin reaction cascade, which in the presence of glucose and hydroxyurea generates a protocell-mediated flux of nitric oxide that we exploit for in vitro and in vivo blood vessel vasodilation. Taken together, our results provide new opportunities for the development of endogenously organized cell-like entities (biocompatible micro-bots) geared specifically towards active interfacing with individual living cells and cell communities.The self-assembly of haemoglobin-containing erythrocyte membrane fragments onto the surface of preformed coacervates has been used to make hybrid synthetic cells that can initiate nitric-oxide-induced vasodilation. These synthetic cells encapsulate enzymes that generate a flux of nitric oxide, as well as exhibiting high haemocompatibility and increased blood circulation times.
Journal Article
Meta-optics empowered vector visual cryptography for high security and rapid decryption
Optical encryption is a promising approach to protecting secret information owing to the advantages of low-power consumption, parallel, high-speed, and multi-dimensional processing capabilities. Nevertheless, conventional strategies generally suffer from bulky system volume, relatively low security level, redundant measurement, and/or requirement of digital decryption algorithms. Here, we propose a general optical security strategy dubbed meta-optics-empowered vector visual cryptography, which fully exploits the abundant degrees of freedom of light as well as the spatial dislocation as key parameters, significantly upgrading the security level. We also demonstrate a decryption meta-camera that can implement the reversal coding procedure for real-time imaging display of hidden information, avoiding redundant measurement and digital post-processing. Our strategy features the merits of a compact footprint, high security, and rapid decryption, which may open an avenue for optical information security and anti-counterfeiting.
Usual methods for optical encryption suffer from a tradeoff between the level of security and the complexity of operation given by multiple optical measurements or digital postprocessing. Here, the authors show a multi-d.o.f. metasurface-based vector optical manipulation protocol enabling secure decryption in real time.
Journal Article
Optimization scheduling of microgrid comprehensive demand response load considering user satisfaction
The original load control model of microgrid based on demand response lacks the factors of incentive demand response, the overall satisfaction of users is low, the degree of demand response is low, the Time Of Use (TOU) price of peak-valley filling capacity is weak, and the peak-valley difference of load curve is large. Regarding the limitations of the current microgrid demand response model, this study further optimizes the flexible load control strategy and proposes a two-objective optimization model based on price and incentive. Meanwhile, the model is solved using an improved chaotic particle group algorithm. Finally, the microgrid load data were selected for simulation analysis. The simulation results showed that the comprehensive demand response of flexible control model proposed increased the overall satisfaction of users by 9.51%, the overall operating cost of microgrid suppliers decreased by 12.975/ten thousand yuan, the peak valley difference decreased by 4.61%, and the user demand response increased by 27.24%. The model effectively improves the overall profit of the supply side of the microgrid, improves the user satisfaction, and maximizes the linkage benefits of the supply and demand of the micro grid. In addition, the model effectively reduces the phenomenon of distributed power supply in the microgrid, and realizes the supply and demand matching of the whole load in the microgrid.
Journal Article
A fast and efficient multiple images encryption based on single-channel encryption and chaotic system
A multiple-image encryption algorithm based on single-channel scrambling, diffusion and chaotic system is presented in this paper. The initial values of the chaotic system are associated with the pixel values of each set of encrypted images as the key for each set of image encryption. The pseudo-random sequences and matrixes generated by the chaotic system are obtained by the corresponding keys, and then, the whole set of images are fused across-image and transferred from the RGB channel to the HSV channel after fusion. For single-channel encryption, select one of the HSV channels is extracted and encryption operations of scrambling and diffusion are performed. The index sequences generated by the chaotic sequences with zero frequency shifting rearrange the pixel positions of the encrypted channel. Combining data splitting, stack storage, and chaotic matrixes, the diffusion operation is achieved. Analyses of the performance show that the algorithm has both excellent encryption speed and security performance.
Journal Article
A Hybrid Optical Fiber Detector for the Simultaneous Measurement of Dust Concentration and Temperature
This work presents a hybrid optical fiber detector by combining the sensing mechanism of the fiber Bragg grating (FBG) and the light extinction method to enable the simultaneous measurement of dust concentration and temperature. Compared with the existing dust concentration sensors, the proposed detector offers three key advantages: intrinsic safety, dual-parameter measurement capability, and potentially network-based monitoring. The critical sensing components of the proposed detector consist of two optical collimators and an FBG. Using the extinction effect of light between the two collimators, the dust concentration and temperature are simultaneously determined by monitoring the intensity and the wavelength of the FBG reflectance spectrum, respectively. The measurement feasibility has been evaluated demonstrating that the two parameters of interest can be effectively sensed with minimally coupled outputs of ±3 pm and ±0.1 mW, respectively. Calibration experiments demonstrate that the change in the intensity of light from the FBG is exponentially related to the dust concentration variation with fitting coefficients equal to 0.948, 0.946, and 0.945 for 200 meshes, 300 meshes, and 400 meshes, respectively. The detector’s relative measurement errors were validated against the weighing method, confirming low measurement deviations.
Journal Article
Dynamical analysis of a new chaotic system: asymmetric multistability, offset boosting control and circuit realization
In this paper, a new four-dimensional dissipative chaotic system which can produce multiple asymmetric attractors is designed and its dynamical behaviors are analyzed. The basin of attraction reveals the asymmetric multistability of the system. In addition, it is very interesting to observe different types of asymmetric coexisting attractors as the bifurcation parameters change. The spectral entropy complexity chaotic diagrams are used to observe the changes in the sequence complexity when the two bifurcation parameters change simultaneously. Moreover, the difference of the system complexity between the two different initial values is analyzed. In order to facilitate engineering applications, the offset boosting control is introduced to the state variable, and the numerical simulation shows that the offset boosting control scheme can flexibly change the polarity of the chaotic signal. Finally, an analog circuit and a digital circuit were designed to verify the new chaotic system. The new research results will enrich the theoretical basis of multistability, offset boosting control and circuit implementation of chaos.
Journal Article