[Research and development practice of traditional Chinese medicine based on network target theory and technology].

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.

Enhanced Sensing Mechanism Based on Shifting an Exceptional Point.

Non-Hermitian systems associated with exceptional points (EPs) are expected to demonstrate a giant response enhancement for various sensors. The widely investigated enhancement mechanism based on diverging from an EP should destroy the EP and further limits its applications for multiple sensing scenarios in a time sequence. To break the above limit, here, we proposed a new enhanced sensing mechanism based on shifting an EP. Different from the mechanism of diverging from an EP, our scheme is an EP nondemolition and the giant enhancement of response is acquired by a slight shift of the EP along the parameter axis induced by perturbation. The new sensing mechanism can promise the most effective response enhancement for all sensors in the case of multiple sensing in a time sequence. To verify our sensing mechanism, we construct a mass sensor and a gyroscope with concrete physical implementations. Our work will deepen the understanding of EP-based sensing and inspire designing various high-sensitivity sensors in different physical systems.

Overexpression of G Protein-Coupled Receptor 40 Protects Obesity-Induced Cardiomyopathy Through the SIRT1/LKB1/AMPK Pathway.

Obesity has become a serious global public health problem, and cardiomyopathy caused by obesity has recently gained attention. As an important protein involved in glucose and lipid metabolism, G protein-coupled receptor 40 (GPR40) exerts cardioprotective effects in some disease models. This study aimed to explore whether GPR40 plays a protective role in obesity-induced cardiomyopathy. We established an obesity model by feeding rats with a high-fat diet, and H9c2 cells were stimulated with palmitic acid to mimic high fat stimulation. Overexpression of GPR40 was achieved by infection with lentivirus or cDNA plasmids. Obesity-induced cardiac injury models exhibit cardiac dysfunction, myocardial hypertrophy, and collagen accumulation, which are accompanied by increased inflammation, oxidative stress, and apoptosis. However, GPR40 overexpression attenuated these alterations. The anti-inflammatory effect of GPR40 may be by inhibiting the nuclear factor-κB pathway, and the antioxidative stress may occur as a result of nuclear transcription factor erythroid 2-related factor 2 pathway activation. In terms of the mechanisms of GPR40 against obese cardiomyopathy, GPR40 overexpression not only activated the sirtuin 1 (SIRT1)-liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway but also enhanced the binding of SIRT1 to LKB1. The antifibrotic, anti-inflammatory, antioxidative stress, and antiapoptotic effects of GPR40 overexpression were inhibited by SIRT1 small interfering RNA. In conclusion, GPR40 overexpression protects against obesity-induced cardiac injury in rats, possibly through the SIRT1-LKB1-AMPK pathway.

[Study on protective effect of vanillic acid from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology screen].

To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data. The monomers of A. membranaceus and their intervention target database were established by using network pharmacology. The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data. An overlap between genes related to cardiac remodeling and targets of ingredients form A. membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling. Angiotensin Ⅱ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A. membranaceus on hypertensive cardiac remodeling. Finally, a total of 81 monomers and 1 197 targets were enrolled in our database. Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice, respectively. Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets, involving 59 monomers from A. membranaceus. Further research found that vanillic acid(VA) could intervene 27 genes associated with hypertensive cardiac remodeling, ranking top 1. Meanwhile, VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length, ANP and BNP mRNA levels in myocardial tissues, myocardial tissue damage, cardiac fibrosis level and cardiac hypertrophy level in vivo. Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.

Self-Assembly of a [2]Pseudorotaxane by an Inchworm-Motion Mechanism.

The threading of biomolecules through pores or channels in membranes is important to validate the physiological activities of cells. To aid understanding of the controlling factors required for the translocation in space with confined size and distorted conformation, it is desirable to identify experimental systems with minimized complexity. We demonstrate the mechanism of a linear guest L1 threading into a tris(crown ether) host TC with a combinational distorted cavity to form a triply interlocked [2]pseudorotaxane 3in-[L1⊂TC]. An inchworm-motion mechanism is proposed for the process. For the forward-threading steps that lead to the formation of higher-order interlocked species, guest L1 must adopt a bent conformation to find the next crown ether cavity. Two simplified models are applied to investigate the self-assembly dynamic of 3in-[L1⊂TC]. Kinetic NMR spectroscopic and molecular dynamics (MD) studies show that formation of the singly penetrated species is fast, whereas formation of the doubly and triply threaded species is several orders of magnitude slower. During threading the freedom of both the guest L1 and host TC gradually decrease due to their interactions. This results in a significant entropy effect for the threading dynamic, which is also observed for the threading of a biomolecular chain through a channel.

Theoretical study of sum-frequency vibrational spectroscopy on limonene surface.

By combining molecule dynamics (MD) simulation and quantum chemistry computation, we calculate the surface sum-frequency vibrational spectroscopy (SFVS) of R-limonene molecules at the gas-liquid interface for SSP, PPP, and SPS polarization combinations. The distributions of the Euler angles are obtained using MD simulation, the ψ-distribution is between isotropic and Gaussian. Instead of the MD distributions, different analytical distributions such as the δ-function, Gaussian and isotropic distributions are applied to simulate surface SFVS. We find that different distributions significantly affect the absolute SFVS intensity and also influence on relative SFVS intensity, and the δ-function distribution should be used with caution when the orientation distribution is broad. Furthermore, the reason that the SPS signal is weak in reflected arrangement is discussed.

Transesterification of rapeseed oil for biodiesel production in trickle-bed reactors packed with heterogeneous Ca/Al composite oxide-based alkaline catalyst.

A conventional trickle bed reactor and its modified type both packed with Ca/Al composite oxide-based alkaline catalysts were studied for biodiesel production by transesterification of rapeseed oil and methanol. The effects of the methanol usage and oil flow rate on the FAME yield were investigated under the normal pressure and methanol boiling state. The oil flow rate had a significant effect on the FAME yield for the both reactors. The modified trickle bed reactor kept over 94.5% FAME yield under 0.6 mL/min oil flow rate and 91 mL catalyst bed volume, showing a much higher conversion and operational stability than the conventional type. With the modified trickle bed reactor, both transesterification and methanol separation could be performed simultaneously, and glycerin and methyl esters were separated additionally by gravity separation.

Effect of calcination temperature on the activity of solid Ca/Al composite oxide-based alkaline catalyst for biodiesel production.

A solid Ca/Al composite oxide-based alkaline catalyst containing Ca(12)Al(14)O(33) and CaO was prepared by chemical synthesis and thermal activation from sodium aluminate solution and calcium hydroxide emulsion. The effect of calcination temperatures ranging from 120 °C to 1000 °C on activity of the catalyst was investigated. The catalyst calcined at 600 °C showed the highest activity with >94% yield of fatty acid methyl esters (i.e. biodiesel) when applied to the transesterification of rapeseed oil at a methanol:oil molar ratio of 15:1 at 65 °C for 3h. Structure and properties of the catalyst were studied and the characterizations with XRD, TGA, FTIR, BET, and SEM demonstrated that the performance of the catalyst was closely related to its specific surface area and crystalline structure. In particular, the generation of crystalline Ca(12)Al(14)O(33) improved the catalytic activity due its synergistic effect with CaO.