Five undescribed plant-derived bisphenols from Artemisia capillaris aerial parts: Structure elucidation,anti-hepatoma activities and plausible biogenetic pathway

Yin-Chen, which belongs to the Asteraceae family and the genus Artemisia, is among the most abundantly used traditional medicines in China for the treatment of hepatitis and bilious disorder. Herein, five undescribed plant-derived bisphenols, capillarisenols A–E (13, 15, 25, 29, 31), and one undescribed phenolic compound (32), together with 32 known phenolic compounds (1–12, 14, 16–24, 26–28, 30, 33–38), were isolated and identified based on spectroscopic evidence from aerial parts of Artemisia capillaris Thunb. Capillarisenols A–E are the type of bisphenols firstly isolated from this plant. The plausible biogenetic pathway of new compounds was also proposed. In addition, the potential anti-hepatoma effects on Huh7 and HepG2 cell lines of all isolated compounds were evaluated in vitro. Capillarisenol C (25) showed significant anti-hepatoma activity in Huh7 and HepG 2 cells, with IC₅₀ values of 4.96 and 8.58 μM, better than the positive control drug (Lenvatinib). This study provided phytochemical evidence for further development and utilisation of A. capillaris in health products.     

Pyrene-tethered bismoviologens for visible light-induced C(sp3)–P and C(sp2)–P bonds formation

Developing efficient photosensitizers for C–P bond construction is highly important and remains a challenge due to the urgently needed for the synthesis of modified nucleosides, nucleotides, and other phosphine-containing ligands. Herein, two pyrene-tethered bismoviologen derivatives (Py-BiV²⁺) were designed and synthesized for visible-light-induced C–P bonds formation. The photochemical and electrochemical properties of Py-BiV²⁺ were studied systemically, certifying fine-tunable opto-electronic properties through the number of pyrene groups (4, n = 1; 6, n = 2). The prepared Py-BiV²⁺ showed strong light absorption, while retaining good redox features and chromic response features that were inherent to viologens. 4 exhibited accelerated photoinduced electron transfer in the presence of the electron donor (pyrene) and the generated 4′ (radical cation) showed higher stability. Accordingly, Py-BiV²⁺ directly served as photosensitizers for the first time in the visible-light-induced C(sp³)–P and C(sp²)–P bonds formation. As expected, these novel viologen derivatives exhibited good catalytic performance and good substrate expansibility under ambient conditions.     

Streptavidin-enhanced surface plasmon resonance biosensor for highly sensitive and specific detection of microRNA

We are presenting a method for sensitive and specific detection of microRNA (miRNA) using surface plasmon resonance. A thiolated capture DNA probe with a short complete complementary sequence was immobilized on the gold surface of the sensor to recognize the part sequence of target miRNA, and then an oligonucleotide probe linked to streptavidin was employed to bind the another section of the target. The use of the streptavidin-oligonucleotide complex caused a ~5-fold increase in signal, improved the detection sensitivity by a factor of ~24, and lowered the detection limit to 1.7 fmol of miR-122. This specificity allowed a single mismatch in the target miRNA to be discriminated. The whole assay takes 30 min, and the surface of the sensor can be regenerated at least 30 times without loss in performance. The method was successfully applied to the determination of miRNA spiked into human total RNA samples.

Novel Triazole Thiole ligand and some of its metal chelates: Synthesis,structure charactertization,thermal behavior in comparison withcomputational caculations andbiological activities

Structural and molecular properties of HL, 4-amino-5-(2,2-dichloro-1-methylcyclopropyl)-4H-1,2,4-triazole-3-thiol toward the transition metal ions namely Fe(III), Co(II) and Ni(II) had been studied using elemental analyses, magnetic, electronic, FT- IR, ¹H-NMR and Thermal analyses (TGA and DTA). The interpretation of thermal decomposition stages had been evaluated. The computations had been done by software of Gaussian 09W package. The geometries of triazole-thiole ligand and its metal chelates were fully optimized using density functional theory B3LYP method. (DFT)/GENECP level by implementing Def2TZVP basis set was used for Fe, Co and Ni-atoms; and basis set 6-311++G (d, p) was used for remainder atoms. There are no symmetry constrains had been applied during geometry optimization. The mixed basis set was selected due to its flexibility. HOMO and LUMO energy values for chelates, chemical hardness and electronegativity had been calculated. NBO calculations had been done at the same level using (NBO 3.1) program involved in the software of Gaussian 09W for measurement qualitatively the intra-molecular delocalization in systems under investigation. The first 15, 85, 65 and 65 low-lying excited states for ligand and Fe, Co and Ni chelates respectively had been calculated within the vertical linear-response. TD-DFT approximation at the same level of theory was used to calculate the electronic absorption spectra of the studied compounds. Their structures are confirmed by successful correlation between experimental and theoretical calculations. The ligand and its metal chelates had been examined against two bacteria such as Gram-positive (Staphylococcus aureus ATTC 12600), GraM–Negative (Escherichia coli ATTC 11775) and two fungus (Aspergillus flavus and Candida albicans) and molecular docking using Auto Dock tools were utilized.     

Systematic evaluation of the mechanisms of zoledronic acid based on network pharmacology

Zoledronic acid (ZA) is an FDA-approved drug and a third-generation bisphosphonate (BPs). A systematic evaluation of the mechanisms of ZA has not previously been performed. In this study, validated targets of ZA were screened using PubChem, Herbal Ingredients’ Targets Database (HIT), Binding Database (BindingDB), and ChemBank, and potential targets of ZA were identified based on structural characteristics of ligands and proteins. The candidate targets were then assessed using GeneMANIA, Gene Ontology (GO), and pathway analysis, and molecule-target-GO-pathway networks were visualized using Cytoscape. Nine validated targets and 26 potential targets were obtained. The networks generated via this analysis showed that the candidate targets were associated with cell proliferation and metabolism as well as other biological processes (BP) and pathways. In general, ZA appeared to play crucial roles in multiple functions, including metabolism, regulation of vascular smooth muscle cell proliferation, and chemical carcinogenesis; a great deal of additional research must be performed. Moreover, the current study showed that it is feasible to analyze the mechanisms of ZA via target prediction, which facilitates systematic pharmacological evaluation.     

Network design with grooming constraints

Networks are physically and logically decomposed into layers with different technological features. Often, the routing of a demand through a non-multiplexing layer is made by grooming several demands at another, multiplexing-capable layer, thus using less capacity on the former but more on the latter. The problem of designing such a multi-layer network so as to route a set of traffic demands can be solved by embedding multiplexing into a well-suited model. We restrict to a two-layer problem as this is most common in today's network world, then we represent grooming through a model based on paths and semi-paths, and propose a row-column generation approach to solve a set of problems on real-world large networks.     

Influence of arm position on proton density fat fraction in the liver using chemical shift-encoded magnetic resonance imaging

PurposeTo evaluate the influence of arm position on B₁ and proton density fat fraction (PDFF) in the liver using chemical shift-encoded magnetic resonance imaging.Materials and methodsParticipants were 8 healthy volunteers without liver disease and 36 patients with presumed or proven fatty liver. We assessed two preliminary examinations in healthy subjects, i.e., arm position influence on B1 and the variability of the PDFF between two scans within a short period of time. To verify the changes in PDFF measurement, 36 patients with fatty liver were conducted to compare 2 different arm positions—the elevated arms and side arms positions. The measurement location was based on the Healey & Schroy classification. The Wilcoxon test was used to analyze the difference in B₁ in between the elevated arms and side arms positions. The Bland-Altman analysis was used to assess the agreement between two measurements of PDFF: two same scans within a short period of time, and two scans with different arms positions.ResultsB₁ was significantly different in all segments except for medial segment. The variability of the PDFF between two scans within a short period of time was small in all segments. Some patients had large fluctuations in all segments, although the mean differences in PDFF were small. Upper and lower limits of agreement were 2.064% to 2.871% and − 2.430% to −1.462%, respectively. The relative difference in the rate of PDFF changes as the median (interquartile range [IQR]) in the lateral, medial, anterior, and posterior segments between both the arms positions were 0.0% (9.4), 1.1% (7.3), 1.5% (8.2) and − 0.2% (10.3), respectively.ConclusionsArm position can significantly affect B₁ and PDFF in the liver. Although the absolute change in PDFF between arm positions was not so large, the difference in arm positions can cause large relative PDFF fluctuations.     

Chemiluminescence imaging for microRNA detection based on cascade exponential isothermal amplification machinery

A novel G-quadruplex DNAzyme-driven chemiluminescence (CL) imaging method was developed for ultrasensitive and specific detection of miRNA based on the cascade exponential isothermal amplification reaction (EXPAR) machinery. A structurally tailored hairpin probe switch was designed to selectively recognise miRNA and form hybridisation products to trigger polymerase and nicking enzyme machinery, resulting in the generation of product I, which was complementary to a region of the functional linear template. Then, the response of the functional linear template to the generated product I further activated the exponential isothermal amplification machinery, leading to synthesis of numerous horseradish peroxidase mimicking DNAzyme units for CL signal transduction. The amplification paradigm generated a linear response from 10 fM to 100 pM, with a low detection limit of 2.91 fM, and enabled discrimination of target miRNA from a single-base mismatched target. The developed biosensing platform demonstrated the advantages of isothermal, homogeneous, visual detection for miRNA assays, offering a promising tool for clinical diagnosis.