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Understanding protein-ligand interactions is crucial to drug discovery and design. However, it would be extremely difficult for the proteins which only have one available apo structure but multiple binding sites. To address this constraint, a fragment-centric topographic mapping method (AlphaSpace software) was employed to map out concave interaction pockets at the assigned protein region. These pockets are used as complementary spaces to screen the known inhibitors for this specific binding site and to guide the molecular docking pose selection as well as protein-ligand interaction analysis. By mapping the shape of central cavity surface, we have tested the strategy against a multi-drug resistant transmembrane protein-ABCG2 to assist in generating a pharmacophore model for its inhibitors that is based on the structure of apo. Classical molecular simulation and accelerated molecular simulation are used to verify the accuracy of inhibitor screening and binding pose selection. Our study not only has gained insight for the development of novel specific ABCG2 inhibitors, but also has provided a general strategy in describing protein-ligand interactions.

A convenient method for the synthesis of 2-oxo-acetamidines from methyl ketones using aromatic amines and DMF as nitrogen sources is reported via copper-catalyzed C(sp3)–H amidination. Various methyl ketones react readily with aromatic amines and DMF, producing 2-oxo-acetamidines in yields of 47 to 92%. This protocol features the simultaneous formation of C–N and CN bonds using DMF and aromatic amines as two different nitrogen sources. It thus provides an efficient approach to construct acyclic amidines via three C(sp3)–H bond amidination. Based on the preliminary experiments, a plausible mechanism of this transformation is disclosed.

Preparation of new materials from biomass is good for sustainable development. Carbon/carbonaceous foams (CFs), as important materials widely applied in both military and civil use, are usually made from nonrenewable materials at high temperature (usually over 1000 °C) and high pressure (at MPa magnitude). Although some biomass raw materials have been used, there is still a fascinating issue waiting to be discussed. That is, what kind of biomass would be suitable for making CFs, or what the biggest challenge might be if these raw materials are used. Herein, a CF with advanced compressibility was made from starch with a simple and energy efficient strategy. The product can be made at much lower temperature (below 500 °C) and pressure (∼190 Pa) than conventional strategies. The understanding of the conversion mechanism provides inspiration for the conversion of other biomass into value-added carbonaceous materials. Due to the presence of reactive groups on the surface of the as-prepared CF, the product can be further modified or used as a substrate to prepare composites for catalysis, phase change energy storage, sensors, water purification, and so on. In this work, its potential application in oil/water separation was demonstrated.

Malignant germ cell tumors (GCTs) such as seminoma and yolk sac tumor cause serious health problems but with favorable prognosis if they were diagnosed timely. To investigate potential biomarkers used for GCTs diagnosis and phenotype distinguishment, we first applied a lncRNA classification pipeline to identify 368 lncRNAs represented on the Affymetrix Human Genome U133A Array. We then comprehensively analyzed the lncRNA expression patterns in a set of previously published gene expression profiles of seminoma and yolk sac tumor stratified by different age groups (children and adults). The lncRNAs expression signatures between children and adults in different GCTs phenotypic groups were identified respectively, five aberrantly expressed lncRNAs were shared by children and adults, indicating a role for them in distinguishing seminoma from yolk sac tumor regardless of age. In parallel, nine distinctive lncRNAs were also determined between seminoma and yolk sac tumor, which suggested that people may face a high risk of suffering from GCTs. Our findings may contribute to the early diagnosis and prognosis of GCTs regardless of patients' age and other diseases.

A convenient method for the synthesis of 2-oxo-acetamidines from methyl ketones using aromatic amines and DMF as nitrogen sources is reported

Solvent etching is a general method for the fabrication of hollow-structured nano/micro-spheres with multiple functions. In this study, we report a facile route for the preparation of hollow composite microspheres, which are amphiphilic and superparamagnetic. In a template of magnetic composite microspheres, P(St-AA)/Fe3O4/PAA, P(St-AA) was selectively etched, resulting in a hydrophobic hollow structure with a shell of hydrophilic polymeric brushes. The effects of etching on the morphology, hollow structure, saturation magnetization, amphiphilic property and cytocompatibility were investigated. Characterization showed that the hollow composite microspheres obtained possessed a well-defined spherical structure, a high saturation magnetization, amphiphilic properties and good cytocompatibility, making them promising as a potential biomaterial in magnetic resonance imaging and drug delivery systems.

In this work, we demonstrate a facile process to synthesize upconversion nanoparticles (UCNPs)@mesoporous SiO2 (mSiO2) core–shell nanoparticles decorated with CdS nanoparticles. The size and morphology of the as-prepared products have been investigated carefully; which show that the UCNPs and CdS nanoparticles are ca. 50 and 5 nm in diameter, respectively, and the mesoporous silica layer is 10 nm in thickness. The fluorescence spectra of the as-prepared UCNPs@mSiO2/CdS nanoparticles show that the fluorescence emissions (380, 451 and 470 nm) have been greatly quenched via energy transitions from the UCNPs nanoparticles (donors) to the CdS nanoparticles (acceptors). CdS nanoparticles were activated by the UCNPs to produce photo-generated ˙OH radicals under irradiation of infrared (IR) light. Photodegradation towards RhB dyes was studied to demonstrate the photocatalytic properties for the as-prepared UCNPs@mSiO2/CdS nanoparticles under irradiation of near infrared light. The as-designed nanostructures of UCNPs@mSiO2/CdS nanoparticles show excellent photocatalytic performance on photodegradation towards RhB under irradiation of infrared light. This kind of nanostructure may find potential applications in photodynamic therapy of cancer cells, for use as nanotransducers, in dyed sensitized solar cells etc.

Recently, amphipathic Janus Fe3O4 nanoparticles, with distinct hydrophilic and hydrophobic “faces”, have attracted tremendous attention. However, conventional synthesis methods for these nanoparticles either influenced the superparamagnetism of Fe3O4 nanoparticles or failed to endow Fe3O4 nanoparticles evident amphipathy, and thus as-prepared amphipathic Janus Fe3O4 nanoparticles hardly reveal remarkable self-assembly properties. To address these critical issues, a versatile strategy that combines activators regenerated by electron transfer for atom transfer radical polymerization (ARGET-ATRP) and Pickering emulsions is proposed here to synthesize amphipathic Janus Fe3O4 nanoparticles for the first time. Owing to the masterly integration all of the unique features of ARGET-ATRP and Pickering emulsions, Janus Fe3O4 nanoparticles with high saturation magnetization and diverse self-assembly behaviors in different solvents are successfully prepared in a gentle, simple and highly controllable reaction condition. Furthermore, these Janus Fe3O4 nanoparticles exhibit prominent emulsification in toluene–water model system as their superior amphipathy. These emulsions could not only maintain excellent stability even in an extremely low usage of Janus Fe3O4 nanoparticles, but also be easily separated by an external magnetic field because of the intrinsic superparamagnetism of Fe3O4. The result implies that the as-received Janus Fe3O4 nanoparticles may have extensive application prospects in oil purification from oil–water compounds. This synthesis strategy likewise could be a guidance to synthesize similar Janus materials.

Pd nanoparticles supported on nitrogen-doped graphene (NG) were prepared as hydrogenation catalysts. Different nitrogen sources (ethylenediamine, ammonia, and urea) were employed to synthesize NG using hydrothermal treatment under mild conditions. The as-made samples were characterized by transmission electron microscopy, scanning electron microscopy, Raman spectroscopy, elemental analysis, nitrogen adsorption–desorption, X-ray diffraction, and X-ray photoelectron spectroscopy. Remarkably improved dispersion of Pd nanoparticles was observed when nitrogen was introduced into the graphene structure. These NG-supported Pd catalysts showed enhanced catalytic hydrogenation activities owing to the superior dispersion of Pd. In the hydrogenation of different olefins, perfect turnover frequencies were obtained over the NG-supported Pd catalyst with urea as the nitrogen source.

A novel method of improving interfacial compatibility in electrospun anion exchange membranes (AEMs) is developed by using imidazolium-functionalized polysulfone (IMPSF) as both electrospun fiber mats and interfiber voids filler. Scanning electron microscopy (SEM) illustrates the defect-free and fiber-retained morphology of the IMPSF electrospun AEMs. Transmission electron microscopy (TEM) shows better aggregation of ion clusters in the IMPSF electrospun AEMs. As a result, the electrospun AEMs prepared in the present work exhibit much higher hydroxide conductivity increment than most reported electrospun AEMs (around 1.7 folds in 20 °C water and 100 folds at 60 °C, relative humidity (RH) 40% as compared with the corresponding cast AEMs). Excellent interfacial compatibility and microphase separation morphology also promote swelling resistance and mechanical and alkaline stabilities of the IMPSF electrospun composite AEMs. Compared with the cast AEMs, tensile strength increment is up to 22%, alkaline stability increases more than one fold after immersing in 1 M KOH at 60 °C for 24 h. Results in the present work are helpful to componential design of the electrospun AEMs.

Shuanghua Baihe tablets (SBT) are a traditional Chinese medicine formula which is used for treatment of oral mucositis (OM) for more than 30 years in China. So far, there has been no report of the quantification of the major components in SBT and their pharmacokinetics in humans. In this study, high performance liquid chromatography coupled to triple-quadrupole mass spectrometry was used to determine the content of the major compounds in SBT and to evaluate the pharmacokinetics of nine major constituents (berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, berberrubine, corynoline and acetylcorynoline) following single and multiple oral administrations of SBT in healthy subjects. This study was an open-label and 2-period clinical trial. It was conducted in 12 Chinese healthy subjects. Each subject received a single dose in period 1 and multiple doses in period 2. Blood samples were collected and determined over 96 h. Subjects underwent safety assessments and were monitored for adverse events. There was no serious adverse event, death or withdrawal. Gender had a significant effect on the pharmacokinetics of the active alkaloids except for magnoflorine, berberrubine, corynoline and acetylcorynoline. Compared with the single dosing, the exposure of the alkaloids increased significantly except for berberrubine after multiple dosing. Single and multiple oral doses of SBT were safe in healthy Chinese subjects. The accumulation of the alkaloids to different extents was observed with repeated dosing except for berberrubine. This work provides useful information for clinical application in the treatment of OM, and a scientific basis for the study on the material foundation of the medicinal effectiveness of SBT and its mechanism of action.

MicroRNAs (miRNAs) are a class of noncoding small RNAs (sRNAs) that play many roles in plant growth, development, and the stress response. Recently, the Brassica napus (B. napus) genome was reported, which allows the genome-wide identification of miRNAs and their targets in B. napus cv. Westar and its transgenic cultivar. Thus, two sRNAs libraries and two degradome libraries of the transgenic B. napus (TG) and its acceptor (B. napus cv. Westar, WA) were constructed. Following high-throughput sequencing and miRNA identification, 139 unique conserved and 305 unique novel miRNA sequences were identified in the two sRNA libraries, and through degradome analysis, 540 targets corresponding to 167 unique miRNA sequences were identified in the two degradome libraries. 11 differentially expressed unique miRNA sequences were verified by quantitative real-time PCR (qRT-PCR), and the results nearly agreed with the high-throughput sequencing data. The present study increases the number of miRNAs identified in B. napus and suggests that there are possible differences in the miRNA expression between transgenic B. napus and its acceptor.

In this study, a series of novel shikonin derivatives (30–49) were designed and synthesized and their anti-proliferative activities were evaluated against five different cancer cell lines, including HeLa, HepG2, MCF-7, BGC and A549. Some of the compounds show strong anti-proliferative effects against HeLa, HepG2 and MCF-7 with IC50 values ranging from 1.26 to 18.50 μM and show lower side effects towards normal cell lines as compared to shikonin. Compared to other compounds and shikonin itself, compound 40 displayed much stronger anti-proliferative effects against various cancer cell lines. Furthermore, the flow cytometry results demonstrated that compound 40 could obviously induce apoptosis in a dose- and time-dependent manner and also cause cell cycle arrest at the G2/M phase. For further investigation of the aforementioned mechanisms, we performed Western blot experiments and found that the cleavage of PARP and upstream caspase-3 increased; moreover, caspase-9 was activated by cleavage but not caspase-8. These aforementioned results also indicate that compound 40 could induce caspase-9 involved apoptosis and G2/M phase cell cycle arrest via the P21, p-CDC2 (Tyr15) pathway independent of P53.

Magnetic polyethyleneimine (PEI) complexes have proven to be simple and efficient carriers for enhanced gene transfection, while the possibility of severe aggregation restricts their further application in vivo. In this study, two negatively charged magnetic nanoparticles (MNPs) with similar sizes but different saturation magnetization values (Ms, 50 and 33 emu g−1 particles, respectively) were synthesized to assemble with PEI–DNA (PD) complexes via electrostatic interaction. The ternary complexes (MPD) that formed showed low levels of aggregation with narrow size distributions (

Apart from chemical molecules, physical regulations also greatly determine the efficiency of healing in regenerating functional tissues. In this study, we fabricated superparamagnetic nano-composite scaffolds for tissue engineering and investigated their effects on different bone cells without an external magnetic field. Poly(lactic-co-glycolic acid) (PLGA) and hydrophobic superparamagnetic magnetite nanoparticles (MNPs) were combined together with different mass ratios in order to construct composite scaffolds using an electrospinning method for the first time. The diameters of the fibers were 400–600 nm with the MNPs uniformly dispersed in them, as shown by transmission (TEM) and scanning (SEM) electron microscopy observations. All composite scaffolds retained superparamagnetism at room temperature, but the saturation magnetization did not increase linearly as the magnetite content increased. The composite scaffolds with different MNP content showed excellent biocompatibility and significantly promoted cell proliferation compared with PLGA nanofibrous scaffold without an external magnetic field. Cell cycle analysis proved that the composite scaffolds decreased cell numbers in G0/G1 phase while increasing those in S phase, which resulted in positive effects on cell proliferation. However, the composite scaffolds had no effect on the differentiation of MC3T3-E1 cells because of the different impact mechanism between proliferation and differentiation. Therefore, the composite scaffolds composed of superparamagnetic MNPs could be considered as an ideal substrate for accelerating osteoblast cell proliferation and tissue repair.