An improved Trizol method for extracting total RNA from Eleutherococcus senticosus (Rupr. & Maxim.) Maxim leaves.

INTRODUCTION: High-quality nucleic acids are the basis for molecular biology experiments. Traditional RNA extraction methods are not suitable for Eleutherococcus senticosus Maxim. OBJECTIVE: To find a suitable method to improve the quality of RNA extracted, we modified the RNA extraction methods of Trizol. METHODOLOGY: Based on the conventional Trizol method, the modified Trizol method 1 and modified Trizol method 2 were used as the control for extraction of RNA from E. senticosus Maxim leaves. The modified Trizol method 1 added ß-mercaptoethanol on the conventional Trizol method. After RNA was dissolved, a mixed solution of phenol, chloroform, and isoamyl alcohol was added to denature protein and inhibit the degradation of RNA. The modified Trizol method 2 adds PVPP to grind on the basis of modified Trizol method 1, so as to better remove phenols from leaves, and eliminates the step of incubation at -20°C to reduce extraction time and RNA degradation. Chloroform, CTAB, and CH3COONa were used instead of a phenol, chloroform, and isoamyl alcohol mixed solution to ensure complete separation of nucleic acid from plant tissues and to obtain high-purity RNA. RESULTS: The research results showed that the quality of RNA extracted by conventional Trizol method, modified Trizol method 1, was incomplete, accompanied with different degrees of contamination of polysaccharides, polyphenols, and DNA. The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. The ratio of A260/A280 was in the range of 1.8-2.0, and the yield of RNA was the highest, which was 1.68 and 1.15 times compared with that by conventional Trizol method and modified Trizol method 1 extraction, respectively. The reverse transcription cDNA was further tested through PCR with the specific primers. The amplified fragments are displayed in clear and bright bands in accordance with the expected size. CONCLUSION: The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. High-quality RNA has more advantages in molecular biology study of E. senticosus Maxim.

Effects of Different Doses of sUV-B Exposure on Taxane Compounds' Metabolism in Taxus wallichiana var. Mairei.

UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. The effects of supplemental ultraviolet-B (sUV-B) exposure (T1, 1.40 kJ·m-2·day-1; T2, 2.81 kJ·m-2·day-1; and T3, 5.62 kJ·m-2·day-1) on the growth biomass, physiological characteristics, and secondary metabolites were studied. Our results indicated that leaf thickness was significantly (p < 0.05) reduced under T3 relative to the control (natural light exposure, CK); The contents of 6-BA and IAA were significantly reduced (p < 0.05); and the contents of ABA, 10-deacetylbaccatin III, and baccatin III were significantly (p < 0.05) increased under T1 and T2. The paclitaxel content was the highest (0.036 ± 0.0018 mg·g-1) under T3. The cephalomannine content was significantly increased under T1. Hmgr gene expression was upregulated under T1 and T3. The gene expressions of Bapt and Dbtnbt were significantly (p < 0.05) upregulated under sUV-B exposure, and the gene expressions of CoA, Ts, and Dbat were significantly (p < 0.05) downregulated. A correlation analysis showed that the 6-BA content had a significantly (p < 0.05) positive correlation with Dbat gene expression. The IAA content had a significantly (p < 0.05) positive correlation with the gene expression of Hmgr, CoA, Ts, and Dbtnbt. The ABA content had a significantly (p < 0.05) positive correlation with Bapt gene expression. Dbat gene expression had a significantly (p < 0.05) positive correlation with the 10-deacetylbaccatin content. Hmgr gene expression was positively correlated with the contents of baccatin III and cephalomannine. Bapt gene expression had a significantly (p < 0.01) positive correlation with the paclitaxel content. A factor analysis showed that the accumulation of paclitaxel content was promoted under T2, which was helpful in clarifying the accumulation of taxane compounds after sUV-B exposure.

Adaptive interference suppression based on an invariant subspace of matrices matching for a horizontal array in underwater acoustics.

Passive detection of target-of-interest (TOI) within strong interferences poses a challenge. This paper introduces an adaptive interference suppression based on an invariant subspace of matrix matching. Assume that the TOI-bearing intervals are known. We define a correlation ratio for each eigenvector to obtain the highest one. Then, we use invariant subspace of matrix matching to measure the distance between two invariant projection matrices of this eigenvector. This identifies and removes the eigenvectors associated with TOI. Finally, the remaining eigenvectors are subtracted from the sample covariance matrix to suppress interference and noise. The viability of the proposed method is demonstrated experimentally.

Study on the photosynthetic growth characters in Cimicifuga dahurica (Turcz.) Maxim under different supplemental light environments.

Cimicifuga dahurica (C. dahurica) is an important medicinal plant in the northern region of China. The best supplemental light environment helps plant growth, development, and metabolism. In this study, we used two-year-old seedlings as experimental materials. The white light as the control (CK). The different ratios of red (R) and blue (B) combined light were supplemented (T1, 2R: 1B, 255.37 µmol m-2·s-1; T2, 3R: 1B, 279.69 µmol m-2·s-1; T3, 7R: 1B, 211.16 µmol m-2·s-1). The growth characteristics, photosynthetic pigment content, photosynthesis and chlorophyll fluorescence parameters, and primary metabolite content were studied in seedlings. The results showed that: 1) The fresh weight from shoot, root, and total fresh weight were significantly (P < 0.05) increased under T2 and T3 treatment. 2) The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) were significantly (P < 0.05) increased under T2 treatment, and carotenoid (car) content was reduced. 3) The photochemical quenching (qP), the actual photosynthetic efficiency of PSII (Y(II)), and the photosynthetic electron transfer rate (ETR) from leaves were significantly (P < 0.05) increased under T1 treatment. The Net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) were significantly (P < 0.05) increased under T2 and T3 treatments. 4) A total of 52 primary metabolites were detected in C. dahurica leaves. Compared with CK, 14, 15, and 18 differential metabolites were screened under T1, T2, and T3 treatments. In addition, D-xylose, D-glucose, glycerol, glycolic acid, and succinic acid were significantly (P < 0.05) accumulated under the T2 treatment, which could regulate the TCA cycle metabolism pathway. The correlation analysis suggested that plant growth was promoted by regulating the change of D-mannose content in galactinol metabolism and amino sugar and nucleotide sugar metabolism. In summary, the growth of C. dahurica was improved under T2 treatment.

A review on separation and application of plant-derived exosome-like nanoparticles.

Exosomes-like nanoparticles (ELNs) (exosomes or extracellular vesicles) are vesicle-like bodies secreted by cells. Plant ELNs (PENs) are membrane vesicles secreted by plant cells, with a lipid bilayer as the basic skeleton, enclosing various active substances such as proteins and nucleic acids, which have many physiological and pathological functions. Recent studies have found that the PENs are widespread within different plant species and their biological functions are increasingly recognized. The effective separation method is also necessary for its function and application. Ultracentrifugation, sucrose density gradient ultracentrifugation, ultrafiltration, polymer-based precipitation methods, etc., are commonly used methods for plant exosome-like nanoparticle extraction. In recent years, emerging methods such as size exclusion chromatography, immunoaffinity capture-based technique, and microfluidic technology have shown advancements compared to traditional methods. The standardized separation process for PENs continues to evolve. In this review, we summarized the recent progress in the biogenesis, components, separation methods, and some functions of PENs. When the research on the separation method of PENs and their unique biological structure is further studied. A brand-new idea for the efficient separation and utilization of PENs can be provided in the future, which has a very broad prospect.

Enzyme-assisted ultrasonic extraction of total flavonoids and extraction polysaccharides in residue from Abelmoschus manihot (L).

Abelmoschus manihot (L) is a traditional chinese herb and the present study focused on its comprehensive development and utilization. Enzyme-assisted ultrasonic extraction (EUAE) was investigated for the extraction and qualitative and quantitative analysis of flavonoids from Abelmoschus manihot (L) using a combination of ultra-performance liquid chromatography-photodiode array (UPLC-PDA), polysaccharides was extracted from residues and compared with directly extracted from raw materials. The optimal yield of 3.46±0.012 % (w/w) was obtained when the weight ratio of cellulase to pectinase was 1:1, the enzyme concentration was 3 %, the pH was 6.0, the solvent was a mixture of 70 % ethanol (v/v) and 0.1 mol/L NaH2PO4 buffer solution, the ultrasonic power was 500 W, the extraction time was 40 min, and the temperature of the extraction was 50 °C. The individual concentrations of interested flavonoids (rutin, neochlorogenic acid, nochlorogenic acid, lsoquercitrin, quercitrin, gossypin, quercetin) were effectively increased with the using of EUAE, compared with ultrasonic extraction (UE) method. Polysaccharides were extracted from each residue, respectively, the Polysaccharides yield in residue from EUAE was higher than that from UE, and closed to the yield from direct extraction in raw materials. The above results shown that the experimental process had the potential to be environmentall, friendly, straightforward and efficient.

Differential Transcriptomic Signatures of Small Airway Cell Cultures Derived from IPF and COVID-19-Induced Exacerbation of Interstitial Lung Disease.

Idiopathic pulmonary fibrosis (IPF) is a pathological condition wherein lung injury precipitates the deposition of scar tissue, ultimately leading to a decline in pulmonary function. Existing research indicates a notable exacerbation in the clinical prognosis of IPF patients following infection with COVID-19. This investigation employed bulk RNA-sequencing methodologies to describe the transcriptomic profiles of small airway cell cultures derived from IPF and post-COVID fibrosis patients. Differential gene expression analysis unveiled heightened activation of pathways associated with microtubule assembly and interferon signaling in IPF cell cultures. Conversely, post-COVID fibrosis cell cultures exhibited distinctive characteristics, including the upregulation of pathways linked to extracellular matrix remodeling, immune system response, and TGF-ß1 signaling. Notably, BMP signaling levels were elevated in cell cultures derived from IPF patients compared to non-IPF control and post-COVID fibrosis samples. These findings underscore the molecular distinctions between IPF and post-COVID fibrosis, particularly in the context of signaling pathways associated with each condition. A better understanding of the underlying molecular mechanisms holds the promise of identifying potential therapeutic targets for future interventions in these diseases.

Transcriptomic and Hormone Analyses Provide Insight into the Regulation of Axillary Bud Outgrowth of Eucommia ulmoides Oliver.

An essential indicator of Eucommia ulmoides Oliver (E. ulmoides) is the axillary bud; the growth and developmental capacity of axillary buds could be used to efficiently determine the structural integrity of branches and plant regeneration. We obtained axillary buds in different positions on the stem, including upper buds (CK), tip buds (T1), and bottom buds (T2), which provided optimal materials for the study of complicated regulatory networks that control bud germination. This study used transcriptomes to analyze the levels of gene expression in three different types of buds, and the results showed that 12,131 differentially expressed genes (DEGs) were discovered via the pairwise comparison of transcriptome data gathered from CK to T2, while the majority of DEGs (44.38%) were mainly found between CK and T1. These DEGs were closely related to plant hormone signal transduction and the amino acid biosynthesis pathway. We also determined changes in endogenous hormone contents during the process of bud germination. Interestingly, except for indole-3-acetic acid (IAA) content, which showed a significant upward trend (p < 0.05) in tip buds on day 4 compared with day 0, the other hormones showed no significant change during the process of germination. Then, the expression patterns of genes involved in IAA biosynthesis and signaling were examined through transcriptome analysis. Furthermore, the expression levels of genes related to IAA biosynthesis and signal transduction were upregulated in tip buds. Particularly, the expression of the IAA degradation gene Gretchen Hagen 3 (GH3.1) was downregulated on day 4, which may support the concept that endogenous IAA promotes bud germination. Based on these data, we propose that IAA synthesis and signal transduction lead to morphological changes in tip buds during the germination process. On this basis, suggestions to improve the efficiency of the production and application of E. ulmoides are put forward to provide guidance for future research.

Supplementary UV-B Radiation Effects on Photosynthetic Characteristics and Important Secondary Metabolites in Eucommia ulmoides Leaves.

To explore the effects of ultraviolet light supplementation on the photosynthetic characteristics and content of secondary metabolites in the leaves of Eucommia ulmoides Oliver (E. ulmoides), the effects of supplementary UV-B (sUV-B) radiation on the medicinally active components of E. ulmoides were comprehensively evaluated. In our study, we selected leaves of five-year-old E. ulmoides seedlings as experimental materials and studied the effect of supplemental ultraviolet-B (sUV-B) radiation on growth, photosynthetic parameters, photosynthetic pigments, fluorescence parameters, and secondary metabolites of E. ulmoides using multivariate analysis. The results showed that the leaf area and the number of branches increased after sUV-B radiation, which indicated that sUV-B radiation was beneficial to the growth of E. ulmoides. The contents of chlorophyll a and chlorophyll b increased by 2.25% and 4.25%, respectively; the net photosynthetic rate increased by 5.17%; the transpiration rate decreased by 35.32%; the actual photosynthetic efficiency increased by 10.64%; the content of the secondary metabolite genipin increased by 12.9%; and the content of chlorogenic acid increased by 75.03%. To identify the genes that may be related to the effects of sUV-B radiation on the growth and development of E. ulmoides leaves and important secondary metabolites, six cDNA libraries were prepared from natural sunlight radiation and sUV-B radiation in E. ulmoides leaves. Comparative analysis of both transcriptome databases revealed a total of 3698 differential expression genes (DEGs), including 1826 up-regulated and 1872 down-regulated genes. According to the KOG database, the up-regulated unigenes were mainly involved in signal transduction mechanisms [T] and cell wall/membrane biogenesis [M]. It is also involved in plant hormone signal transduction and phenylpropanoid biosynthesis metabolic pathways by the KEGG pathway, which might further affect the physiological indices and the content of chlorogenic acid, a secondary metabolite of E. ulmoides. Furthermore, 10 candidate unigenes were randomly selected to examine gene expression using qRT-PCR, and the six libraries exhibited differential expression and were identical to those obtained by sequencing. Thus, the data in this study were helpful in clarifying the reasons for leaf growth after sUV-B radiation. And it was beneficial to improve the active components and utilization rate of E. ulmoides after sUV-B radiation.

Development of a Coal Dust Concentration Sensor Based on the Electrostatic Induction Method.

In order to solve the problems of easy blockage and difficult maintenance of the current coal dust concentration sensor, a coal dust concentration sensor based on the electrostatic induction method was designed. Based on the analysis of the principle of electrostatic induction dust concentration detection, an electrostatic induction dust concentration sensor composed of a electrostatic detection electrode, a dust extraction fan, an induction signal processing circuit, an insulator, a shield, and other parts was designed. The influence of the length and width of the electrostatic detection electrode and the particle flow rate on the standard deviation of the induction signal was analyzed through experiments to optimize them. The induction signals on the electrostatic detection electrode at different dust concentrations were determined in tests, and the mathematical relationship between the standard deviation of the induction signal and the dust concentration was obtained. According to segment multiple-curve height fitting, the maximum deviation between the detected value and actual dust concentration does not exceed 10%.

A New Construction of 4q-QAM Golay Complementary Sequences.

Quadrature amplitude modulation (QAM) constellation and Golay complementary sequences (GCSs) are usually applied in orthogonal frequency division multiplexing (OFDM) systems to obtain a higher data rate and a lower peak-to-mean envelope power ratio (PMEPR). In this paper, after a sufficient search of the literature, it was found that increasing the family size is an effective way to improve the data rate, and the family size is mainly determined by the number of offsets in the general structure of QAM GCSs. Under the guidance of this idea, we propose a new construction for 4q-QAM GCSs through generalized Boolean functions (GBFs) based on a new description of a 4q-QAM constellation, which aims to enlarge the family size of GCSs and obtain a low PMEPR. Furthermore, a previous construction of 4q-QAM GCSs presented by Li has been proved to be a special case of the new one, and the family size of new sequences is much larger than those previously mentioned, which means that there was a great improvement in the data rate. On the other hand, a previous construction of 16-QAM GCSs presented by Zeng is also a special case of the new one in this paper, when q=2. In the meantime, the proposed sequences have the same PMEPR upper bound as the previously mentioned sequences presented by Li when applied in OFDM systems, which increase the data rate without degrading the PMEPR performance. The theoretical analysis and simulation results show that the proposed new sequences can achieve a higher data rate and a low PMEPR.

Micromechanism Analysis of Surfactant Wetting of Coal Based on 13C NMR Experiments.

With the gradual improvement in coal mine mechanization and automation, the dust concentration at production sites is increasing significantly as the production efficiency improves, which not only poses a substantial threat to the occupational safety and health of workers but also affects the safe production and social stability of mines. At present, wet dust removal is the most economical and effective technical dust removal measure. However, most coal seams in China have poor wettability, unclear microscopic wetting mechanisms, and poor dust removal effects. Therefore, based on experiments and numerical analysis, this paper qualitatively studies the influencing factors of surfactants on coal wettability and quantitatively constructs an innovative evaluation model of the influence of the microstructure of coal and surfactants on wettability. First, based on 13C NMR experiments, the structural parameters of coal and several surfactants were obtained. Second, the wettability relationship between the coal and the surfactants was determined by optical titration, and the key factors affecting the wettability of coal dust and the wettability of the surfactants were selected. Then, using numerical analysis and function fitting analysis and combining the structural parameters with the coal wetting results, the relationship between the microstructure of the surfactants on different kinds of coal and the wettability of the coal samples was established. The results show that the ether group, the phenol or aromatic ether carbon, the fatty methyl group, and the aromatic methyl group in the surfactants have a substantial influence on the wettability. The research results can provide scientific guidance for the development of efficient and environmentally friendly compound dust suppressants to realize clean production in mines.

Bioinspired Multifunctional Cellular Plastics with a Negative Poisson's Ratio for High Energy Dissipation.

Cellular plastics have been widely used in transportation, aerospace, and personal safety applications owing to their excellent mechanical, thermal, and acoustic properties. It is highly desirable to impart them with a complex porous structure and composition distribution to obtain specific functionality for various engineering applications, which is challenging with conventional foaming technologies. Herein, it is demonstrated that this can be achieved through the controlled freezing process of a monomer/water emulsion, followed by cryopolymerization and room temperature thawing. As ice is used as a template, this method is environmentally friendly and capable of producing cellular plastics with various microstructures by harnessing the numerous morphologies of ice crystals. In particular, a cellular plastic with a radially aligned structure shows a negative Poisson's ratio under compression. The rigid plastic shows a much higher energy dissipation capability compared to other materials with similar negative Poisson's ratios. Additionally, the simplicity and scalability of this approach provides new possibilities for fabricating high-performance cellular plastics with well-defined porous structures and composition distributions.

Efficient Water Transport and Solar Steam Generation via Radially, Hierarchically Structured Aerogels.

A nature-inspired water-cycling system, akin to trees, to perform effective water and solar energy management for photosynthesis and transpiration is considered to be a promising strategy to solve water scarcity issues globally. However, challenges remain in terms of the relatively low transport rate, short transport distance, and unsatisfactory extraction efficiency. Herein, enlightened by conifer tracheid construction, an efficient water transport and evaporation system composed of a hierarchical structured aerogel is reported. This architecture with radially aligned channels, micron pores, and molecular meshes is realized by applying a radial ice-template method and in situ cryopolymerization technique. This nature-inspired design benefits the aerogel excellent capillary rise performance, realizing a long-distance (>28 cm at 190 min) and quick (>1 cm at 1 s, >9 cm at 300 s) antigravity water transport on a macroscopic scale, regardless of clean water, seawater, sandy groundwater, or dye-including effluent. Furthermore, an efficient water transpiration and collection is performed by the bilayer-structured aerogel with a carbon heat collector on an aerogel top, demonstrating a solar steam generation rate of 2.0 kg m-2 h-1 with the energy conversion efficiency up to 85.7% under one solar illumination. This biomimetic design with the advantage of water transport and evaporation provides a potential approach to realize water purification, regeneration, and desalination.

Transparent Impact-Resistant Composite Films with Bioinspired Hierarchical Structure.

Inspired by the helicoidally organized microstructure of stomatopods' smasher dactyl club, a type of impact-resistant composite film reinforced with periodic helicoidal nanofibers is designed and fabricated, which reproduces the structural complexity of the natural material. To periodically align nanofibers in a helicoidal structure, an electrospinning system is developed to better control the alignment of electrospun nanofibers. When the nanofiber scaffold is embedded in an epoxy matrix, the presence of a hierarchical structure allows the composite films to achieve properties well beyond their constituents. The composite film exhibits excellent optical transparency and mechanical properties, such as enhanced tensile strength, ductility, and defect tolerance. With elegant design mimicking nature's hierarchical structure at multilength scales, the composite films could effectively release the impact energy and greatly increase the impact resistance, suggesting that the transparent composite films are promising protective layers suitable for various applications.

A Thermally Insulating Textile Inspired by Polar Bear Hair.

Animals living in the extremely cold environment, such as polar bears, have shown amazing capability to keep warm, benefiting from their hollow hairs. Mimicking such a strategy in synthetic fibers would stimulate smart textiles for efficient personal thermal management, which plays an important role in preventing heat loss and improving efficiency in house warming energy consumption. Here, a "freeze-spinning" technique is used to realize continuous and large-scale fabrication of fibers with aligned porous structure, mimicking polar bear hairs, which is difficult to achieve by other methods. A textile woven with such biomimetic fibers shows an excellent thermal insulation property as well as good breathability and wearability. In addition to passively insulating heat loss, the textile can also function as a wearable heater, when doped with electroheating materials such as carbon nanotubes, to induce fast thermal response and uniform electroheating while maintaining its soft and porous nature for comfortable wearing.

Metabolomics Characterization of Two Apocynaceae Plants, Catharanthus roseus and Vinca minor, Using GC-MS and LC-MS Methods in Combination.

Catharanthus roseus (C. roseus) and Vinca minor (V. minor) are two common important medical plants belonging to the family Apocynaceae. In this study, we used non-targeted GC-MS and targeted LC-MS metabolomics to dissect the metabolic profile of two plants with comparable phenotypic and metabolic differences. A total of 58 significantly different metabolites were present in different quantities according to PCA and PLS-DA score plots of the GC-MS analysis. The 58 identified compounds comprised 16 sugars, eight amino acids, nine alcohols and 18 organic acids. We subjected these metabolites into KEGG pathway enrichment analysis and highlighted 27 metabolic pathways, concentrated on the TCA cycle, glycometabolism, oligosaccharides, and polyol and lipid transporter (RFOS). Among the primary metabolites, trehalose, raffinose, digalacturonic acid and gallic acid were revealed to be the most significant marker compounds between the two plants, presumably contributing to species-specific phenotypic and metabolic discrepancy. The profiling of nine typical alkaloids in both plants using LC-MS method highlighted higher levels of crucial terpenoid indole alkaloid (TIA) intermediates of loganin, serpentine, and tabersonine in V. minor than in C. roseus. The possible underlying process of the metabolic flux from primary metabolism pathways to TIA synthesis was discussed and proposed. Generally speaking, this work provides a full-scale comparison of primary and secondary metabolites between two medical plants and a metabolic explanation of their TIA accumulation and phenotype differences.

Yhhu4488, a novel GPR40 agonist, promotes GLP-1 secretion and exerts anti-diabetic effect in rodent models.

G protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic ß-cells and activated by long-chain fatty acids. GPR40 has drawn considerable interest as a potential therapeutic target for type 2 diabetes mellitus (T2DM) due to its important role in enhancing glucose-stimulated insulin secretion (GSIS). Encouragingly, GPR40 is also proven to be highly expressed in glucagon-like peptide-1 (GLP-1)-producing enteroendocrine cells afterwards, which opens a potential role of GPR40 in enhancing GLP-1 secretion to exert additional anti-diabetic efficacy. In the present study, we discovered a novel GPR40 agonist, yhhu4488, which is structurally different from other reported GPR40 agonists. Yhhu4488 showed potent agonist activity with EC50 of 49.96 nM, 70.83 nM and 58.68 nM in HEK293 cells stably expressing human, rat and mouse GPR40, respectively. Yhhu4488 stimulated GLP-1 secretion from fetal rat intestinal cells (FRIC) via triggering endogenous calcium store mobilization and extracellular calcium influx. The effect of yhhu4488 on GLP-1 secretion was further confirmed in type 2 diabetic db/db mice. Yhhu4488 exhibited satisfactory potency in in vivo studies. Single administration of yhhu4488 improved glucose tolerance in SD rats. Chronic administration of yhhu4488 effectively decreased fasting blood glucose level, improved ß-cell function and lipid homeostasis in type 2 diabetic ob/ob mice. Taken together, yhhu4488 is a novel GPR40 agonist that enhances GLP-1 secretion, improves metabolic control and ß-cell function, suggesting its promising potential for the treatment of type 2 diabetes.

Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors.

The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 µM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.

Synthesis and biological evaluation of 2,4,5-substituted pyrimidines as a new class of tubulin polymerization inhibitors.

Members of a series of 2,4,5-substituted pyrimidine derivatives were synthesized, and their interactions with tubulin and their antiproliferative activities against the human hepatocellular carcinoma cells of liver (BEL-7402) were evaluated. One member of this family, the indole-pyrimidine 4k, having an indole-aryl-substituted aminopyrimidine structure, was observed to be an excellent inhibitor of tubulin polymerization (IC(50) = 0.79 µM) and to display significantly high antiproliferative activities against several cancer cell lines with IC(50) values ranging from 16 to 62 nM. This substance displayed a high propensity to arrests cells at the G(2)/M phase of the cell cycle (EC(50) = 20 nM). In addition, 4k was found to competitively inhibit colchicine binding to tubulin, indicating that it binds to the colchicine-binding site of tubulin. The observations made in this investigation demonstrate that 2,4,5-substituted pyrimidines represent a new class of tubulin polymerization inhibitors with significant antiproliferative activity.