Uncovering Mechanism and Efficacy of Salvia Miltiorrhiza-Safflower in Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia (CI) is the main cause of stroke morbidity and disability. This study aims to identify the early molecular regulation responsible for the therapeutic effectiveness of the Herb pair Danshen-Honghua (DH) for CI. The major targets of DH were identified by searching the public database of traditional Chinese medicine (TCM). In addition, GeneCards, Disgenet, and GeneMap databases in OMIM were used to determine the disease targets of CI. A total of 88 common targets of DH and CI were selected, a protein-protein interaction (PPI) network was established by Cytoscape, and 19 core targets were screened. These genes were primarily enriched in biological processes including wound healing, reaction to oxidative stress, and response to peptides, lipid and atherosclerosis, Age-rage signaling pathway, and TNF signaling pathway by KEGG and GO enrichments. The effective components of DH had stable binding to these key targets by molecular docking. Finally, it was verified that the mechanism of DH on CI treatment may be related to the activation of the TNF-α/JNK signaling pathway by establishing the middle cerebral artery occlusion (MCAO) rat model.

Multi-target meridians classification based on the topological structure of anti-cancer phytochemicals using deep learning.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) meridian is the key theoretical guidance of prescription against tumor in clinical practice. However, there is no scientific and systematic verification of therapeutic action of herbs under meridians context. Several studies have determined the Chinese herbal medicine (CHM) phytochemicals for intrinsic attribute or meridians classification based on artificial intelligence (AI) tools. However, it is challenging to represent the complex molecular structures with large heterogeneity through the current technologies. In addition, the multiple correspondence between herbs and meridians has not been paid much attention. AIM OF THE STUDY: We aim to develop an AI framework to classify multi-target meridians through the topological structure of phytochemicals. MATERIALS AND METHODS: A total of 354 anti-cancer herbs, their corresponding TCM meridians and 5471 ingredient compounds were collected from public databases of CancerHSP, ETCM, and Hit 2.0. The statistical analysis of herbal and compound datasets, clustering analysis of the associated cancers, and correlational analysis of meridian tropism were preliminary conducted. Then a deep learning (DL) hybrid model named GRMC consisting of graph convolutional network (GCN) and recurrent neural network (RNN) was employed to generate the meridian multi-label sequences based on molecular graph. RESULTS: The curing herbs against tumors have tight relationships to lung, liver, stomach, and spleen meridians. These herbs behave different properties in curing certain cancer. Certain cancer types have co-occurrence such as ovarian, bladder and cervical cancer. Compounds have multitarget meridians with characteristics of higher-order correlations. Compared with the other state-of-the-art algorithms on the datasets and previous methods dealing with conventional fixed fingerprints of herbal compounds, the proposed GRMC has superior overall performance on testing dataset with the one error of 0.183, hamming loss of 0.112, mean averaged accuracy (MAA) of 0.855, mean averaged precision (MAP) of 0.891, mean averaged recall (MAR) of 0.812, and mean averaged F1 score (MAF) of 0.849. CONCLUSIONS: The proposed method can predict multi-targeted meridians through neural graph features in herbal compounds and outperforms several comparison methods. It could provide a basis for understanding the molecular scientific evidence of TCM meridians.

Protein Recognition Based on Temperature-Stimulated Multiparameter Response Virtual Array Sensing Strategy.

In the field of array sensing, researchers are committed to miniaturizing array sensing systems while ensuring the acquisition of multiple sensing information. Here, a new strategy called "stimulus responsive array sensing" was presented to obtain virtual multiple sensing without constructing multiple physical sensing units. Based on bioluminescence resonance energy transfer, where luciferase acts as the donor and temperature stimulus response polymers act as the receptors, by using only one sensing unit to output multiple stimulus responsive sensing signals in temperature dimension, an equivalent array sensing could be achieved. This strategy can distinguish and quantify a variety of proteins. More importantly, glucose responsive monomers were doped in polymers; thus, more virtual sensing units can be further increased to obtain more sensing signals, greatly increasing the accuracy of protein recognition, and it can also be used to differentiate several compositions of protein under different glucose concentrations in urine caused by different renal diseases. The results show the potential of the "stimulus responsive array sensing" for analyzing molecular compositions in complex biological systems and show a new tack in array sensing.

Chiral zinc oxide functionalized quartz crystal microbalance sensor for enantioselective recognition of amino acids.

Chiral transition metal oxides with tunable structures and multiple physicochemical features have been increasingly applied for chiral sensing and detection. In this work, chiral zinc oxide (ZnO) was first applied as selector to construct quartz crystal microbalance (QCM) sensor for enantioselective recognition of amino acids. The chiral ZnO was prepared by a methionine-induced self-assembly strategy and its high topological chirality was confirmed by several techniques such as circular dichroism spectrum. The chiral discrimination factors were calculated by frequency shifts in response to aspartic acid, phenylalanine, lysine and arginine on L-ZnO surface, achieving 1.89 ± 0.04, 1.76 ± 0.11, 1.66 ± 0.07 and 1.54 ± 0.09, respectively. Notably, L-enantiomers preferred stronger absorptions on L-ZnO surface as compared to D-forms. It was further found that this sensor was appropriate for quantitative analysis and enantiomer excess analysis and adsorption kinetics study. Furthermore, molecular docking revealed the recognition mechanism, where chiral distinction was caused by the different steric interactions between enantiomers and chiral ZnO. This method enjoyed merits of high enantioselectivity, simple preparation and low cost, offering newly chiral sensing method for other molecules.

Pickering emulsion-enhanced Vibrio fischeri assay for ecotoxicity assessment of highly hydrophobic polycyclic aromatic hydrocarbons.

Accurate ecotoxicity assessment of contaminated soil is critical to public health, and the luminescent bacteria (Vibrio fischeri) method is the most commonly used. Hydrophobic compounds such as polycyclic aromatic hydrocarbons (PAHs) in soil cannot be in contact with luminescent bacteria due to their low water solubility so that the luminescence inhibitory effect cannot be observed. The underestimated biological toxicity makes the test unreliable and en-dangers public health and safety. The commonly adopted improved method of adding cosolvents has limited effect, it was only effective for low-hydrophobicity chemicals and could not be used for ecotoxicity evaluation of high-hydrophobicity chemicals. Therefore, we constructed Pickering emulsions using luminescent bacteria modified with n-dodecanol in which PAHs were dissolved in the oil phase, n-tetradecane. Then the luminescent bacteria could tightly adhere to the oil-water interface and contact PAHs. As a result, their bioluminescence was suppressed to varying degrees depending on the chemical species and concentrations. With no solubility limitation, highly hydrophobic PAHs could even completely inhibit bacterial bioluminescence, hence the toxicity information was accurately displayed and the median effect concentration (EC50) values could be calculated. This Pickering emulsion-based method was successfully applied for the accurate ecotoxicity evaluation of highly hydrophobic PAHs and soil samples contaminated with them, which all previous methods could not achieve. This method overcomes the problem of ecotoxicity evaluation of hydrophobic compounds, and has great potential for practical application, whether it is pure chemicals or various real samples from the ecological environment.

Allele-specific expression and chromatin accessibility contribute to heterosis in tea plants (Camellia sinensis).

Heterosis is extensively used to improve crop productivity, yet its allelic and chromatin regulation remains unclear. Based on our resolved genomes of the maternal TGY and paternal HD, we analyzed the contribution of allele-specific expression (ASE) and chromatin accessibility of JGY and HGY, the artificial hybrids of oolong tea with the largest cultivated area in China. The ASE genes (ASEGs) of tea hybrids with maternal-biased were mainly related to the energy and terpenoid metabolism pathways, whereas the ASEGs with paternal-biased tend to be enriched in glutathione metabolism, and these parental bias of hybrids may coordinate and lead to the acquisition of heterosis in more biological pathways. ATAC-seq results showed that hybrids have significantly higher accessible chromatin regions (ACRs) compared with their parents, which may confer broader and stronger transcriptional activity of genes in hybrids. The number of ACRs with significantly increased accessibility in hybrids was much greater than decreased, and the associated alleles were also affected by differential ACRs across different parents, suggesting enhanced positive chromatin regulation and potential genetic effects in hybrids. Core ASEGs of terpene and purine alkaloid metabolism pathways with significant positive heterosis have greater chromatin accessibility in hybrids, and were potentially regulated by several members of the MYB, DOF and TRB families. The binding motif of CsMYB85 in the promoter ACR of the rate-limiting enzyme CsDXS was verified by DAP-seq. These results suggest that higher numbers and more accessible ACRs in hybrids contribute to the regulation of ASEGs, thereby affecting the formation of heterotic metabolites.

Monitoring of the yogurt fermentation process based on a rapid bio-luminescent chiral pattern recognition of amino acids.

The analysis of chiral α-amino acids is of great significance in asymmetric synthesis, nutrition, food science, and microbiology. However, the ability of chiral recognition is difficult to achieve. Due to the demand for expensive equipment and skilled operators, traditional methods such as high-performance liquid chromatography are limited. The previously reported methods based on chemical sensor arrays usually cannot carry out the chiral analysis. Here, we developed a novel biosensor array based on the interaction between a suite of host-based luminescent bacteria and amino acids and used linear discriminant analysis to reflect their luminescence response patterns. This biosensor array could effectively discriminate chiral amino acids, including 19 L-amino acids, their corresponding D-enantiomers, and the achiral glycine. In addition, the determination of enantiomeric purity and quantitative ability has been proved. The successful identification of a complex system containing multiple chiral amino acids further demonstrates the superiority of the bioluminescent sensor array. Moreover, this sensor array could efficiently monitor the dynamic composition of free amino acids in the process of milk fermentation. Finally, the bioluminescence response mechanism of the luminescent bacteria for the recognition of chirality was clarified. This approach possessed the advantages of facile construction, high throughput, easy operation, high accuracy and fast response.

Preparation of DNA-functionalized surfaces for simultaneous homeotropic orientation of liquid crystals and optical recognition of analytes: application to the determination of progesterone.

The work describes a simplified method for the preparation of liquid crystal (LC) bioassay using DNA-based capture molecules and having lower detection limits. The capture DNA probes of the stem-loop structure were immobilized on the surface of a glass slide. A homeotropic orientation of LC molecules can be obtained with the proper surface coverage of capture DNA probes. In the presence of analytes (specifically shown here for the progesterone as a model analyte), the molecular binding between capture DNA probes and progesterone opens the loop of the capture DNA probes. The opened sequence is then amenable to hybridization with a reporter DNA probe that is immobilized on gold nanoparticles. This changes the surface microstructure, disrupts the orientation of LC molecules, and results in an enhanced optical response, expressed as the average grey value of the images. This new kind of surface treatment for simultaneous recognition of target molecules and homeotropic anchoring of LCs reduces the number of preparation steps and makes the process of LC bioassay easier. This method has a detection limit as low as 0.1 pmol·L-1 of progesterone. Graphical abstract Schematic presentation of the liquid crystal-based DNA assay. DMOAP: Dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride; TEA: Triethoxsilylbutyraldehyde; 5CB: 4-cyano-4'-pentylbiphenyl; P4: progesterone.

Detection of sulfadimethoxine using optical images of liquid crystals.

A label-free method for sulfadimethoxine (SDM) detection using an aptamer-based liquid crystal biosensor is developed. The sensor probe is fabricated by immobilizing amine-functionalized aptamers onto the glass slide decorating mixed self-assembled layers of triethoxysilylbutyraldehyde (TEA) and N,N-dimethyl-n-octadecyl-3-aminopropyltrimethoxysilylchloride (DMOAP). Liquid crystals (LCs) are supported on the surface and serve as response elements, which assume the homeotropic alignment and cause a dark optical appearance under crossed polarizers. In the presence of SDM, the formation of SDM-aptamer compounds induces a notable change in the topographical structure of the surface, which disturbs the original homeotropic orientation of LCs and results in a bright optical appearance. A detection limit of 10 µg L-1 is obtained, which is far lower than the maximum residue limit (100 µg L-1 in China). This facile method shows good specificity for SDM detection and may have great potential for detecting other small molecules.

Comprehensive assessment of association between TLR4 gene polymorphisms and cancer risk: a systematic meta-analysis.

Previous studies have explored the association between toll-like receptor 4 (TLR4) polymorphisms and risk of various cancers, but the results remained controversial. To obtain an assessment of the effect of TLR4 polymorphisms (rs4986790, rs4986791 and rs11536889) on cancer risk, fifty-five articles (containing 20107 cases and 28244 controls) were recruited for meta-analysis. Our result indicated that two Single Nucleotide Polymorphisms (SNP) in TLR4 were associated with decreased cancer risk for rs4986791: OR = 0.764, 95% CI: 0.652-0.894, P = 0.001 in allele model; OR = 0.769, 95%CI: 0.650-0.909, P = 0.002 in recessive model; OR = 0.505, 95% CI: 0.352-0.726, P = 0.000 in dominant model; for 11536889: OR = 0.927, 95% CI: 0.872-0.984, P = 0.013 in allele model; OR = 0.926, 95% CI: 0.862-0.944,P = 0.034 in recessive model. In terms of subgroup analyses sorted by ethnicity, only polymorphism of rs4986791 had a significant influence on decrease of cancer risk among both Caucasian and Asian populations. The findings suggested that TLR4 polymorphisms may serve as a genetic risk factor for cancers.