Host-guest complex solid state molecular motion is a critical but underexplored phenomenon. In principle, it can be used to control molecular machines that function in the solid state. Here we ...describe a solid state system that operates on the basis of complexation between an all-hydrocarbon macrocycle, D
-CDMB-8, and perylene. Molecular motion in this solid state machine is induced by exposure to organic solvents or grinding and gives rise to different co-crystalline, mixed crystalline, or amorphous forms. Distinct time-dependent emissive responses are seen for different organic solvents as their respective vapours or when the solid forms are subject to grinding. This temporal feature allows the present D
-CDMB-8⊃perylene-based system to be used as a time-dependent, colour-based 4th dimension response element in pattern-based information codes. This work highlights how dynamic control over solid-state host-guest molecular motion may be used to induce a tuneable temporal response and provide materials with information storage capability.
Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently ...intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma.
•A new strategy is proposed for studying the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients.•The new strategy explains why TCM ingredients with low ...bioavailability could have high activity in vivo.•The active forms of PD with antitussive and expectorant effects are its intestinal microbiota metabolites.
The intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue.
A new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed.
Platycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking.
Results showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-β-d-glucopyranosyl platycodigenin, 3-O-β-d-glucopyranosyl isoplatycodigenin, 7‑hydroxyl-3-O-β-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism.
The proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.
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We report the symmetry-dictated mesophase formation and phase diagram of a series of T8-polyhedral oligomeric silsesquioxane (POSS) derivatives bearing perfluoroalkyl chains and hydroxyl alkyl ...groups. The phase structures and phase behaviors of these molecular Janus particles were studied by DSC, POM, FT-IR, and WAXD experiments. It was found that introducing one hydroxyl alkyl group leads to a decreased crystal melting point, and incorporating two hydroxyl alkyl groups at different POSS positions causes the formation of lamellar liquid crystal mesophases with feature sizes and transition temperatures that depend on the symmetry of these regioisomers. Interestingly, installing only one substituent with two hydroxyl groups leads to monotropic phase transitions, where the mesophase appears only upon cooling from the isotropic melt within the narrow supercooling window. Phase diagrams were systematically constructed for these compounds and understood based on the fine influence of symmetry on their possible molecular packing scheme and their distinct hydrogen bonding patterns, as evidenced by their infrared spectra at different temperatures. These results are not only fundamental to understanding the effects of regioisomerism on giant molecule self-assembly but also important for the development of hybrid materials with tailored nanostructures.
Catheter ablation has become an important treatment for atrial fibrillation (AF), but its recurrence rate is still high. The aim of this study was to predict AF recurrence using a three-dimensional ...(3D) network model based on body-surface potential mapping signals (BSPMs). BSPMs were recorded with a 128-lead vest in 14 persistent AF patients before undergoing catheter ablation (Maze-IV). The torso geometry was acquired and meshed by point cloud technology, and the BSPM was interpolated into the torso geometry by the inverse distance weighted (IDW) method to generate the isopotential map. Experiments show that the isopotential map of BSPMs can reflect the propagation of the electrical wavefronts. The 3D isopotential sequence map was established by combining the spatial–temporal information of the isopotential map; a 3D convolutional neural network (3D-CNN) model with temporal attention was established to predict AF recurrence. Our study proposes a novel attention block that focuses the characteristics of atrial activations to improve sampling accuracy. In our experiment, accuracy (ACC) in the intra-patient evaluation for predicting the recurrence of AF was 99.38%. In the inter-patient evaluation, ACC of 3D-CNN was 81.48%, and the area under the curve (AUC) was 0.88. It can be concluded that the dynamic rendering of multiple isopotential maps can not only comprehensively display the conduction of cardiac electrical activity on the body surface but also successfully predict the recurrence of AF after CA by using 3D isopotential sequence maps.
The optoelectronic oscillators (OEOs) based on a 1.55-μm direct-modulated AlGaInAs/InP square microcavity laser without optical injection are demonstrated for narrow-linewidth photonic microwave ...signal generation. The square microcavity laser with a side length of 16 μm under an injection current of 14 mA is used in the experiment. High-quality photonic microwave signals with 3-dB linewidths around 30 Hz are obtained by the first harmonics of the single-loop and dual-loop OEOs. Single-sideband phase noise at 10 kHz frequency offset is as low as -116 dBc/Hz for the microwave signal. With the dual-loop OEO, the side-mode suppression ratios up to 55 dB are obtained for the first harmonics, and tunable microwave signals from 1.85 to 10.24 GHz are realized with narrow linewidths and low-phase noises.
The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. ...Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.
This paper investigates the vibration control problem for offshore platform, where the nonlinear characteristics, delayed input and external wave force are considered in time domain. By introducing a ...delay‐free reconstructional vector and applying the maximum principle, the original vibration problem for offshore platform is formulated as a nonlinear two‐point‐boundary‐value (TPBV) problem with delayed items. The major contribution of this paper is that a performance‐based near‐optimal vibration control strategy is proposed by solving this nonlinear TPBV problem, which includes a feedback item with offshore platform system state, a feedforward item with wave force state, and a compensator for nonlinear and delayed items with infinite supersensitive component. In particular, the designed compensator is calculated from two group series of linear differential equations by introducing a parameter for expending the Maclaurin series of nonlinear and delay items. Meanwhile, an iterative algorithm is designed to make the proposed vibration control scheme computable based on the control performance in each iterative procedure. Finally, experimental results show that the displacement, velocity and performance index of an employed offshore platform achieved small values under the proposed control strategy and designed algorithm.
Related studies have shown that the time characteristics of microblog can improve retrieval performance. However, these researches mainly focus on the time distribution of tweets related to a given ...query. And this single time characteristics might not be sufficient to reflect time characteristics of microblog. Inspired by the recent success of time-based language models for microblog retrieval, this paper proposes a time segment language model (TSLM) to model the time characteristics of microblog. Briefly, TSLM constructs the language model of each time segment to model the probability distribution over sequences of words for each different time segment. Based on TSLM, the time distribution of terms (tDT), the time distribution of queries (tDQ) and the time distribution of documents (tDD) are proposed. Furthermore, TSLM is exploited to estimate the query model, the document model and compute the similarity between query and document. The experimental results on the Tweets2011 corpus show that the proposed approaches outperform several state-of-the-art baselines.
Long noncoding RNAs (lncRNAs) may serve as specific targets for the treatment of abdominal aortic aneurysms (AAAs). LncRNA GAS5, functionally associated with smooth muscle cell (SMC) apoptosis and ...proliferation, is likely involved in AAA formation, but the exact role of GAS5 in AAA is unknown. We thus explored the contribution of GAS5 to SMC-regulated AAA formation and its underlying mechanisms.
: Human specimens were used to verify the diverse expression of GAS5 in normal and AAA tissues. The angiotensin II (Ang II)-induced AAA model in ApoE-/- mice and the CaCl
-induced AAA model in wild-type C57BL/6 mice were used. RNA pull-down and luciferase reporter gene assays were performed in human aortic SMCs to detect the interaction between GAS5 and its downstream targets of protein or microRNA (miR).
GAS5 expression was significantly upregulated in human AAA specimens and two murine AAA models compared to human normal aortas and murine sham-operated controls. GAS5 overexpression induced SMC apoptosis and repressed its proliferation, thereby promoting AAA formation in two murine AAA models. Y-box-binding protein 1 (YBX1) was identified as a direct target of GAS5 while it also formed a positive feedback loop with GAS5 to regulate the downstream target p21. Furthermore, GAS5 acted as a miR-21 sponge to release phosphatase and tensin homolog from repression, which blocked the activation and phosphorylation of Akt to inhibit proliferation and promote apoptosis in SMCs.
The LncRNA GAS5 contributes to SMC survival during AAA formation. Thus, GAS5 might serve as a novel target against AAA.
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