Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus-bile acid-intestinal farnesoid X receptor axis based on multiomics integration analysis.

Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic-based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus-bile acid-intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.

Drought responses and population differentiation of Calohypnum plumiforme inferred from comparative transcriptome analysis.

Bryophytes, known as poikilohydric plants, possess vegetative desiccation-tolerant (DT) ability to withstand water deficit stress. Consequently, they offer valuable genetic resources for enhancing resistance to water scarcity stress. In this research, we examined the physiological, phytohormonal, and transcriptomic changes in DT mosses Calohypnum plumiforme from two populations, with and without desiccation treatment. Comparative analysis revealed population differentiation at physiological, gene sequence, and expression levels. Under desiccation stress, the activities of superoxide dismutase (SOD) and peroxidase (POD) showed significant increases, along with elevation of soluble sugars and proteins, consistent with the transcriptome changes. Notable activation of the bypass pathway of JA biosynthesis suggested their roles in compensating for JA accumulation. Furthermore, our analysis revealed significant correlations among phytohormones and DEGs in their respective signaling pathway, indicating potential complex interplays of hormones in C plumiforme. Protein phosphatase 2C (PP2C) in the abscisic acid signaling pathway emerged as the pivotal hub in the phytohormone crosstalk regulation network. Overall, this study was one of the first comprehensive transcriptome analyses of moss C. plumiforme under slow desiccation rates, expanding our knowledge of bryophyte transcriptomes and shedding light on the gene regulatory network involved in response to desiccation, as well as the evolutionary processes of local adaptation across moss populations.

Accelerating Ethanol Complete Electrooxidation via Introducing Ethylene as the Precursor for the C-C Bond Splitting.

The crucial issue restricting the application of direct ethanol fuel cells (DEFCs) is the incomplete and sluggish electrooxidation of ethanol due to the chemically stable C-C bond thereof. Herein, a unique ethylene-mediated pathway with a 100 % C1-selectivity for ethanol oxidation reaction (EOR) is proposed for the first time based on a well-structured Pt/Al2 O3 @TiAl catalyst with cascade active sites. The electrochemical in situ Fourier transform infrared spectroscopy (FTIR) and differential electrochemical mass spectrometry (DEMS) analysis disclose that ethanol is primarily dehydrated on the surface of Al2 O3 @TiAl and the derived ethylene is further oxidized completely on nanostructured Pt. X-ray absorption and density functional theory (DFT) studies disclose the Al component doped in Pt nanocrystals can promote the EOR kinetics by lowering the reaction energy barriers and eliminating the poisonous species. Strikingly, Pt/Al2 O3 @TiAl exhibits a specific activity of 3.83 mA cm-2 Pt , 7.4 times higher than that of commercial Pt/C and superior long-term durability.

In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS.

3,4,5,4'-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in ApcMin/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireXTM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model ApcMin/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the ApcMin/+ mice's intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.

Pathogenicity Variation in Two Genomes of Cercospora Species Causing Gray Leaf Spot in Maize.

The gray leaf spots caused by Cercospora spp. severely affect the yield and quality of maize. However, the evolutionary relation and pathogenicity variation between species of the Cercospora genus is largely unknown. In this study, we constructed high-quality reference genomes by nanopore sequencing two Cercospora species, namely, C. zeae-maydis and C. zeina, with differing pathogenicity, collected from northeast (Liaoning [LN]) and southeast (Yunnan [YN]) China, respectively. The genome size of C. zeae-maydis-LN is 45.08 Mb, containing 10,839 annotated genes, whereas that of Cercospora zeina-YN is 42.18 Mb, containing 10,867 annotated genes, of which approximately 86.58% are common in the two species. The difference in their genome size is largely attributed to increased long terminal repeat retrotransposons of 3.8 Mb in total length in C. zeae-maydis-LN. There are 41 and 30 carbohydrate-binding gene subfamilies identified in C. zeae-maydis-LN and C. zeina-YN, respectively. A higher number of carbohydrate-binding families found in C. zeae-maydis-LN, and its unique CBM4, CBM37, and CBM66, in particular, may contribute to variation in pathogenicity between the two species, as the carbohydrate-binding genes are known to encode cell wall-degrading enzymes. Moreover, there are 114 and 107 effectors predicted, with 47 and 46 having unique potential pathogenicity in C. zeae-maydis-LN and C. zeina-YN, respectively. Of eight effectors randomly selected for pathogenic testing, five were found to inhibit cell apoptosis induced by Bcl-2-associated X. Taken together, our results provide genomic insights into variation in pathogenicity between C. zeae-maydis and C. zeina. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke.

Ischemic stroke (IS) is a common neurological disorder associated with high disability rates and mortality rates. At present, recombinant tissue plasminogen activator (r-tPA) is the only US(FDA)-approved drug for IS. However, due to the narrow therapeutic window and risk of intracerebral hemorrhage, r-tPA is currently used in less than 5% of stroke patients. Natural compounds have been widely used in the treatment of IS in China and have a wide range of therapeutic effects on IS by regulating multiple targets and signaling pathways. The keywords "ischemia stroke, traditional Chinese Medicine, Chinese herbal medicine, natural compounds" were used to search the relevant literature in PubMed and other databases over the past five years. The results showed that JAK/STAT, NF-κB, MAPK, Notch, Nrf2, and PI3K/Akt are the key pathways, and SIRT1, MMP9, TLR4, HIF-α are the key targets for the natural compounds from traditional Chinese medicine in treating IS. This study aims to update and summarize the signaling pathways and targets of natural compounds in the treatment of IS, and provide a base of information for the future development of effective treatments for IS.

Prediction of the mechanism of Dachengqi Decoction treating colorectal cancer based on the analysis method of " into serum components -action target-key pathway".

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) is a common digestive tract malignant tumor that its morbidity and mortality seriously affect human health. At present, Dachengqi Decoction (DCQ), a traditional Chinese medicine formula, has been clinically used as an adjuvant therapy for CRC. However, pharmacodynamic substance basis and therapeutic mechanism are still unclear. AIM OF THE STUDY: The main constituents absorbed in the blood and possible active targets after DCQ administration were explored based on the analysis method of "into serum components, action target and key pathway", which may provide reference for the study of the pharmacodynamic material basis and action mechanism of Dachengqi Decoction in the treatment of CRC. MATERIAL AND METHODS: Based on the serum pharmacochemistry of traditional Chinese medicine (TCM), the prescription prototype ingredients of DCQ in mice serum samples were identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology (UPLC-Q-TOF-MSE). Taking the prototype ingredients absorbed into serum as the research object, the possible targets and key pathways of DCQ in vivo were demonstrated by network pharmacology. Finally, using molecular docking verified the binding activity of prototype components and potential action targets. RESULTS: A total of 46 prototype components of DCQ were identified in mice serum, most of which were derived from flavonoids and anthraquinones in Citrus aurantium L. and Rheum palmatum L. Network pharmacology prediction results indicated that the drug prototype components entering the serum may mainly regulate targets including mitogen-activated protein kinase (MAPK), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. and main pathways such as (phosphatidylinositol 3-kinase/protein kinase B) PI3K-AKT signaling pathway, advanced glycation end products-receptor for AGE (AGE-RAGE) signaling pathway and IL-17 signaling pathway, etc. Molecular docking showed that the prototype active components had strong binding activity to VEGF, Harvey rat sarcoma viral oncogene homolog (HRAS) and MAPK1. CONCLUSIONS: This study elucidated that most of the direct acting substances of DCQ in vivo were flavonoids and anthraquinones, which may play a role in regulating cell reproduction and apoptosis and inhibiting inflammation, providing a reference for the research of pharmacodynamic material basis and mechanism of DCQ in the treatment of CRC.

Elaeagnus angustifolia can improve salt-alkali soil and the health level of soil: Emphasizing the driving role of core microbial communities.

Saline-alkali environments are widely distributed in China and significantly hinder the development of agriculture. This study characterizes the long-term effects of planting Elaeagnus angustifolia (E. angustifolia) on the physical and chemical properties, enzyme activities and microbial community characteristics of saline-alkali soil in the Songnen Plain (1, 2 and 3 years). The results showed that planting E. angustifolia reduced soil pH and electrical conductivity (EC) and increased soil total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (Nni), total potassium (TK), dissolved organic C (DOC), dissolved organic matter (DOM) and available potassium (AK) content and catalase, urease, polyphenol oxidase, phosphatase, sucrase and cellulase enzyme activities, and the results peaked in the 3 year. High-throughput sequencing showed that the bacterial abundance and diversity were as follows (from high to low) y3 > y2 > y1 > CK. E. angustifolia resulted in an increase in the relative abundance of the dominant bacteria. Proteobacteria and Pseudomonas were the major phylum and genus, respectively. Redundancy analysis showed that changes in the soil microbial community significantly affect the physical and chemical properties of the soil, with Proteobacteria members being the key microorganisms that reduce soil salinity. Network analysis showed that Pseudomonas (Proteobacteria) participated in the synthesis of key soil enzymes. 16S rRNA sequencing predicted that the expression of genes related to carbon (rbcL, acsA, acsB, Pcc and accA) and nitrogen (amoA/B, nxrA, hao, gdh, ureC and nosZ) transformation increased, and Pseudomonas members were key regulators of carbon and nitrogen dynamics. In conclusion, the planting of E. angustifolia could improve the physical and chemical properties of the soil by releasing root exudates into the soil and increasing the diversity and richness of soil microbial communities to improve saline-alkali soil, providing a theoretical basis for improving saline-alkali soil and promoting the sustainable development of modern agriculture.

Acetic acid acting as a signaling molecule in the quorum sensing system increases 2,3-butanediol production in Saccharomyces cerevisiae.

2,3-Butanediol (2,3-BD) has been extensively used in chemical syntheses. This study aimed to explore acetic acid as a signaling molecule that activates a quorum sensing (QS) system to promote the production of 2,3-BD. The yield of 2,3-BD is proportional to the cell density. Saccharomyces cerevisiae W141 does not produce 2,3-BD when the cell density is lower than the threshold concentration (OD600 nm = 10 or cell density 4.4 × 108 CFU/mL). When 1.5 g/L acetic acid is added, the yield of 2,3-BD is 3.01 ± 0.04 g/L. Subsequently, S. cerevisiae W141 was cocultured with Acetobacter pasteurianus Huniang 1.01 under the optimal conditions, the acetic acid production was increased by 76.7% and 30.6% compared with the original strain and the strain cultivated with 1.5 g/L acetic acid, and the yield of 2,3-BD was increased by 81.9% and 3.3%, respectively. This difference is due to the activity of acetyl lactic acid synthase (ILV2) and 2,3-BD dehydrogenase (BDH1), as the relative expression of the ilv2 and bdh1 genes is increased. The results showed that the biosynthesis of 2,3-BD was regulated by acetic acid as a signaling molecule. S. cerevisiae is a promising host for producing 2,3-BD for industrial applications.

Enhanced ß-mannanase production by Bacillus licheniformis by optimizing carbon source and feeding regimes.

Bacillus licheniformis HDYM-04 was isolated in flax retting water and showed ß-mannanase activity. Carbon sources for ß-mannanase production, as well as the fermentation conditions and feeding strategy, were optimized in shake flasks. When glucose or konjac powder was used as the carbon source, the ß-mannanase activity was 288.13 ± 21.59 U/mL and 696.35 ± 23.47 U/mL at 24 h, respectively, which was approximately 4.4- to 10.68-fold higher than the values obtained with wheat powder. When 0.5% (w/v) glucose and 1% (w/v) konjac powder were added together, maximum enzyme activities of 789.07 ± 25.82 U/mL were obtained, an increase of 13.35% compared to the unoptimized cultures with only 1% (w/v) konjac powder. The enzyme activity decreased in the presence of 1% (w/v) konjac powder, but the highest enzyme activity was 1,533.26 ± 33.74 U/mL, a 1.2-fold increase compared with that in nonoptimized cultures; when 0.5% (w/v) glucose was used, the highest enzyme activity was 966.53 ± 27.84 U/mL, an increase in ß-mannanase activity of 38.79% compared with control cultures. In this study, by optimizing fed-batch fermentation conditions, the yield of ß-mannanase produced by HDYM-04 was increased, laying the foundation for the industrial application and further research of B. licheniformis HDYM-04.

Intraspecific and interspecific quorum sensing of bacterial community affects the fate of antibiotic resistance genes during chicken manure composting under penicillin G stress.

In this study, the effects of penicillin G (PENG) on the fate of bacterial communities and ß-lactamase antibiotic resistance genes (ARGs) during chicken manure composting were assessed, to illustrate the roles of PENG in ARGs behavior. The results showed that the total absolute abundances of 9 ARGs and 4 mobile genetic elements (MGEs) was significantly increased by PENG (P < 0.05). Dozens of potential hosts for ARGs were predominantly affiliated with Firmicutes, Proteobacteria, and Actinobacteria. Meanwhile, the higher concentration of PENG significantly increased the abundance of luxI and luxS in quorum sensing (QS) (P < 0.05), which enhanced the frequency of inter/intraspecific gene "communication." Redundancy analysis and structural equation modeling further revealed that QS had a strong regulatory role in horizontal gene transfer of ARGs mediated via MGEs. These results provide new insight into the mechanism of ARGs propagation in aerobic composting modified by PENG.

The Voice of Drug Consumers: Online Textual Review Analysis Using Structural Topic Model.

Many web-based pharmaceutical e-commerce platforms allow consumers to post open-ended textual reviews based on their purchase experiences. Understanding the true voice of consumers by analyzing such a large amount of user-generated content is of great significance to pharmaceutical manufacturers and e-commerce websites. The aim of this paper is to automatically extract hidden topics from web-based drug reviews using the structural topic model (STM) to examine consumers' concerns when they buy drugs online. The STM is a probabilistic extension of Latent Dirichlet Allocation (LDA), which allows the consolidation of document-level covariates. This innovation allows us to capture consumer dissatisfaction along with their dynamics over time. We extract 12 topics, and five of them are negative topics representing consumer dissatisfaction, whose appearances in the negative reviews are substantially higher than those in the positive reviews. We also come to the conclusion that the prevalence of these five negative topics has not decreased over time. Furthermore, our results reveal that the prevalence of price-related topics has decreased significantly in positive reviews, which indicates that low-price strategies are becoming less attractive to customers. To the best of our knowledge, our work is the first study using STM to analyze the unstructured textual data of drug reviews, which enhances the understanding of the aspects of drug consumer concerns and contributes to the research of pharmaceutical e-commerce literature.

High-throughput metabolomics reveals the perturbed metabolic pathways and biomarkers of Yang Huang syndrome as potential targets for evaluating the therapeutic effects and mechanism of geniposide.

High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites. This study used the established Yang Huang syndrome (YHS) mouse model to evaluate the efficacy of geniposide (GEN). Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry. The non-target screening of the massive biological information dataset was performed, and a total of 33 metabolites, including tyramine glucuronide, aurine, and L-cysteine, were identified relating to YHS. These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin. Interestingly, they were completely reversed by GEN. While, as the auxiliary technical means, we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part. We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology. This study is the first to report that GEN indirectly regulates the metabolite "tyramine glucuronide" through its direct effect on the target heme oxygenase 1 in vivo. Meanwhile, heme oxygenase-1, a prediction of network pharmacology, was the confirmed metabolic enzyme of phase I reaction in hepatocytes. Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine (TCM) syndrome.

High-throughput liquid chromatography mass-spectrometry-driven lipidomics discover metabolic biomarkers and pathways as promising targets to reveal the therapeutic effects of the Shenqi pill.

Lipidomics, a branch of metabonomics, could provide a powerful technique for discovery of lipid molecules to reveal disease status and drug efficacy. The Shenqi pill (SQP) is a representative prescription for clinical application in the prevention and treatment of kidney-yang deficiency syndrome (KYDS). However, its effect mechanism is still not clear. This article aims to reveal the intervention effect of SQP on KYDS from the perspective of lipid metabolism. In this study, SQP was used to intervene in the rat model of KYDS, on the foundation of successfully replicating the rat model of KYDS induced by corticosterone. The MetaboAnalyst tool was used for analysis of the serum metabolic profile and pattern recognition of KYDS model, based on UPLC-SYNAPT-G2-Si-HDMS. Finally, twenty-two potential lipid biomarkers related to the KYDS model were characterized, and the effects of SQP on regulating potential lipid markers in serum of KYDS model were analyzed. There were 10 biomarkers and seven metabolic pathways closely related to SQP therapy for KYDS were found. The action mechanism and targets of SQP in treating KYDS were explored based on high-throughput lipidomics. This work could provide valuable data and scientific evidence in subsequent studies for the treatment of KYDS.

Ultra-performance liquid chromatography/mass spectrometry technology and high-throughput metabolomics for deciphering the preventive mechanism of mirabilite on colorectal cancer via the modulation of complex metabolic networks.

Colorectal cancer (CRC) is a highly virulent and malignant disease and always accompanied by metabolic disorders. Currently, there are no effective therapeutic drugs for the treatment of CRC. High-throughput metabolomics approaches have been used to unveil the metabolic pathways related to several diseases. In this study, ultra-performance liquid chromatography/mass spectrometry-based high-throughput metabolomics was used for deciphering the potential preventive mechanism of mirabilite on CRC via the modulation of the associated metabolic disorders; a total of 28 differential biomarkers, including indole acetaldehyde, 5-hydroxyindoleacetic acid, hypoxanthine, retinal, retinal ester, linoleic acid, stearic acid, 6-deoxocastasterone, 2-hydroxybutyric acid and LysoPC, were identified in the APCmin/+ mice. These differential biomarkers are involved in the tryptophan metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Note that these biomarkers and their disturbed metabolic pathways were also regulated by mirabilite. It has been found that the prevention of CRC by mirabilite is mainly associated with tryptophan metabolism; this study shows that high-throughput metabolomics can reveal the perturbed metabolic disorders targeted in the action mechanism of drug treatment.

Network pharmacology combined with functional metabolomics discover bile acid metabolism as a promising target for mirabilite against colorectal cancer.

In this study, a combination of network pharmacology and metabolomics was used to explore the mechanism by which mirabilite regulates bile acid metabolism in the treatment of colorectal cancer. The PharmMapper web server was applied to make preliminary predictions for the treatment targets of mirabilite and to predict the interaction between mirabilite and disease targets using Discovery Studio 2.5. Furthermore, the urine metabolic profile was analyzed by the UPLC-Q-TOF-MS technology. The original data were processed by Progenesis QI software and analyzed by multivariate pattern recognition, which allowed us to reveal the metabolic disturbance in colorectal cancer and explain the therapeutic effect of mirabilite. The network pharmacology results showed that mirabilite can act on the disease targets, and the sites of action include amino acid residues Arg-364 and Asp-533, as well as nucleotides TPC-11, DG-112 and DA-113. Based on metabolomics, potential biomarkers were found to lie in the relevant pathways of bile acid metabolism, such as taurine, chenodeoxycholic acid, cholic acid, and deoxycholic acid. The results showed that mirabilite could regulate the distribution of overall metabolic disturbance, and bile acid metabolism was the main targeted pathway. Additionally, we predicted the upstream targets by ingenuity pathway analysis and found that mirabilite played a significant role in regulating the bile acid-related biomarkers, which allowed comprehensive analysis of the effect of mirabilite on colorectal cancer. This study fully explained the role of mirabilite in inhibiting colorectal cancer, which mainly occurs through bile acid metabolism, via the approach of network pharmacology combined with functional metabolomics.

High-throughput lipidomics reveal mirabilite regulating lipid metabolism as anticancer therapeutics.

Altered lipid metabolism is an emerging hallmark of cancers. Mirabilite has a therapeutic effect on colorectal cancer (CRC); however, its metabolic mechanism remains unclear. This study aims to explore the potential therapeutic targets of mirabilite protection against colorectal cancer in APCmin/+ mice model. Oral administration of mirabilite was started from the ninth month, while the same dosage of distilled water was given to both the control group and the model group. Based on lipidomics, we collected serum samples of all mice at the 20th week and used a non-targeted method to identify the lipid biomarkers of CRC. Compared with C57BL/6J mice, the metabolic profile of CRC model mice was significantly disturbed, and we identified that 25 lipid-related biomarkers, including linoleic acid, 2-hydroxybutyric acid, 6-deoxocastasterone, hypoxanthine, PC(16:1), PC(18:4), and retinyl acetate, were associated with CRC. According to the abovementioned results, there were six lipid molecules with significant differences that can be used as new targets for handling of CRC through six metabolic pathways, namely, linoleic acid metabolism, retinol metabolism, propanoate metabolism, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and purine metabolism. Compared with the model group, the metabolic profiles of these disorders tend to recover after treatment. These results indicated that the lipid molecules associated with CRC were regulated by mirabilite. In addition, we identified seven key lipid molecules, of which four had statistical significance. After administration of mirabilite, all disordered metabolic pathways showed different degrees of regulation. In conclusion, high-throughput lipidomics approach revealed mirabilite regulating the altered lipid metabolism as anticancer therapeutics.

Fatigue Resistant Bioinspired Composite from Synergistic Two-Dimensional Nanocomponents.

Portable and wearable electronics require much more flexible graphene-based electrode with high fatigue life, which could repeatedly bend, fold, or stretch without sacrificing its mechanical properties and electrical conductivity. Herein, a kind of ultrahigh fatigue resistant graphene-based nanocomposite via tungsten disulfide (WS2) nanosheets is synthesized by introducing a synergistic effect with covalently cross-linking inspired by the orderly layered structure and abundant interfacial interactions of nacre. The fatigue life of resultant graphene-based nanocomposites is more than one million times at the stress level of 270 MPa, and the electrical conductivity can be kept as high as 197.1 S/cm after 1.0 × 105 tensile testing cycles. These outstanding properties are attributed to the synergistic effect from lubrication of WS2 nanosheets for deflecting crack propagation, and covalent bonding between adjacent GO nanosheets for bridging crack, which is verified by the molecular dynamics (MD) simulations. The WS2 induced synergistic effect with covalent bonding offers a guidance for constructing graphene-based nanocomposites with high fatigue life, which have great potential for applications in flexible and wearable electronic devices, etc.

Metabolomics and proteomics technologies to explore the herbal preparation affecting metabolic disorders using high resolution mass spectrometry.

An integrative metabolomics and proteomics approach can provide novel insights in the understanding of biological systems. We have integrated proteome and metabolome data sets for a holistic view of the molecular mechanisms in disease. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UPLC-Q-TOF-HDMS based metabolomics, we determined the protein and metabolite expression changes in the kidney-yang deficiency syndrome (KYDS) rat model and further investigated the intervention effects of the Jinkui Shenqi Pill (JSP). The VIP-plot of the orthogonal PLS-DA (OPLS-DA) was used for discovering the potential biomarkers to clarify the therapeutic mechanisms of JSP in treating KYDS. The results showed that JSP can alleviate the kidney impairment induced by KYDS. Sixty potential biomarkers, including 5-l-glutamyl-taurine, phenylacetaldehyde, 4,6-dihydroxyquinoline, and xanthurenic acid etc., were definitely up- or down-regulated. The regulatory effect of JSP on the disturbed metabolic pathways was proved by the established metabonomic method. Using pathway analyses, we identified the disturbed metabolic pathways such as taurine and hypotaurine metabolism, pyrimidine metabolism, tyrosine metabolism, tryptophan metabolism, histidine metabolism, steroid hormone biosynthesis, etc. Furthermore, using iTRAQ-based quantitative proteomics analysis, seventeen differential proteins were identified and significantly altered by the JSP treatment. These proteins appear to be involved in Wnt, chemokine, PPAR, and MAPK signaling pathways, etc. Functional pathway analysis revealed that most of the proteins were found to play a key role in the regulation of metabolism pathways. Bioinformatics analysis with the IPA software found that these differentially-expressed moleculars had a strong correlation with the α-adrenergic signaling, FGF signaling, etc. Our data indicate that high-throughput metabolomics and proteomics can provide an insight on the herbal preparations affecting the metabolic disorders using high resolution mass spectrometry.

High-throughput chinmedomics-based prediction of effective components and targets from herbal medicine AS1350.

This work was designed to explore the effective components and targets of herbal medicine AS1350 and its effect on "Kidney-Yang Deficiency Syndrome" (KYDS) based on a chinmedomics strategy which is capable of directly discovering and predicting the effective components, and potential targets, of herbal medicine. Serum samples were analysed by UPLC-MS combined with pattern recognition analysis to identify the biomarkers related to the therapeutic effects. Interestingly, the effectiveness of AS1350 against KYDS was proved by the chinmedomics method and regulated the biomarkers and targeting of metabolic disorders. Some 48 marker metabolites associated with alpha-linolenic acid metabolism, fatty acid metabolism, sphingolipids metabolism, phospholipid metabolism, steroid hormone biosynthesis, and amino acid metabolism were identified. The correlation coefficient between the constituents in vivo and the changes of marker metabolites were calculated by PCMS software and the potential effective constituents of AS1350 were also confirmed. By using chinmedomics technology, the components in AS1350 protecting against KYDS by re-balancing metabolic disorders of fatty acid metabolism, lipid metabolism, steroid hormone biosynthesis, etc. were deduced. These data indicated that the phenotypic characterisations of AS1350 altering the metabolic signatures of KYDS were multi-component, multi-pathway, multi-target, and overall regulation in nature.