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[Display omitted] • Nanomedicine (CaNP/DOX/Cyt c) is pH-responsive in the tumor region. • Simultaneous loading of chemotherapeutics and proteins. • Two drugs carried by nanomedicine (CaNP/DOX/Cyt c) has synergistic antitumor effect. • Nanomedicine (CaNP/DOX/Cyt c) reduces toxicity and side effects. Intracellular co-delivery of proteins and chemotherapeutics provides a promising strategy for synergistic cancer therapy. However, the lack of delivery systems for controlled intracellular release of both payloads and effective endosomal escape of proteins significantly hinders the anticancer applications of this strategy. Herein, we designed a pH-responsive calcium carbonate mineralization nanoparticle system for concurrent delivery of cytochrome c (Cyt c) and doxorubicin (DOX) into the cytosol. The dual-drug loaded nanoparticles (CaNP/DOX/Cyt c) exhibited high stability under physiological conditions but acid-sensitive intracellular release of DOX and Cyt c, and also mediated efficient endosomal escape of Cyt c. As a result, the DOX underwent efficient delivery into the nuclei, and Cyt c successfully got into the cytosol as demonstrated by the confocal laser scanning microscopy. Furthermore, CaNP/DOX/Cyt c mediated enhanced synergistic anti-osteosarcoma effects with significantly improved biocompatibility as demonstrated both in vitro and in vivo. In summary, this work highlights the potential of calcium carbonate mineralized nanoparticle system as a universal and potent platform for efficient intracellular co-delivery of proteins and chemotherapeutics. [ABSTRACT FROM AUTHOR]

Two new germacrane sesquiterpenes, yedoensins A ( 1 ) and B ( 2 ), together with 8 known ones ( 3 – 10 ) were isolated from the herb of Viola yedoensis . The structures of the new compounds were established by extensive spectroscopic means including 1D ( 1 H and 13 C) and 2D NMR experiments (HSQC, HMBC, and NOESY) as well as HR-ESI-MS analysis. The absolute configurations of the known sesquiterpenes versicolactone B ( 3 ) and madolin W ( 6 ) were determined by a modified Mosher's method for the first time. The sesquiterpenes 1–3 , and 5 – 9 exhibited anti-complement activity against the classical pathway (CP) and the alternative pathway (AP) with the CH 50 and AP 50 values ranging from 0.14 to 0.37 mg/mL and 0.32 to 0.54 mg/mL, respectively. Preliminary mechanism study using complement-depleted sera showed that yedoensin A ( 1 ) and versicolactone B ( 3 ) acted on C1q, C3 and C9, while madolin W ( 6 ), aristoyunnolin E ( 7 ) and madolin Y ( 9 ) interacted with C1q, C3, C5 and C9 components in the complement activation cascade. [ABSTRACT FROM AUTHOR]

• Propose a novel parallel mechanism for loading test of hydraulic support. • Establish the explicit direct position solutions of this mechanism. • Present the good transmission orientation workspace of this mechanism. • Compare the orientation capability under different dimensional parameters. A novel 1T2R parallel mechanism (PM), applied in loading test of hydraulic support, is proposed, whose kinematic performance is studied in detail. The analytical expression of forward kinematic positions are derived by means of vector method. With the aid of Jacobian matrix, the singular configurations are investigated. The orientation capacity of end-effector is depicted through the azimuth and tilt angles. Using screw theory as the mathematical tool, this paper establishes the evaluation indices for motion/force transmission performance such as input transmission index, output transmission index and local transmission index (LTI). The definitions and calculation methods of good transmission orientation workspace (GTOW), regular transmission orientation workspace, and average transmission index in regular workspace are presented, respectively. Furthermore, the distributions of GTOW and the surface of LTI are plotted. Finally, the analysis results indicate that PU-RPU-UPS PM has good kinematic performances, which can be used as loading actuator of the new hydraulic support test-bed. [ABSTRACT FROM AUTHOR]

Abstract: A high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC–ELSD) has been developed to evaluate the quality of Asparagus filicinus through a simultaneous determination of six steroidal saponins and one ecdysone, including aspafiliosides A, B, C, E, G, filiasparoside A and 20-hydroxyecdysone. With a C18 analytical column, the seven analytes were separated efficiently using acetonitrile–water as the mobile phase in a gradient program. The method limits of detection ranged 0.125–0.225μg, and the method limits of quantitation ranged 0.408–0.720μg, respectively. The intra- and inter-day precisions of the method were evaluated and were all less than 3%. All the recoveries for the spiked analytes ranged 95.16%–100.61%. The proposed method was successfully applied to quantify the seven components in thirteen samples from different localities in China. [Copyright &y& Elsevier]

Summary: The diffusible signal factor (DSF)-dependent quorum sensing (QS) system adopts a novel protein-protein interaction mechanism to autoregulate the production of signal DSF. Here, we present the crystal structures of DSF synthase RpfF and its complex with the REC domain of sensor protein RpfC. RpfF is structurally similarity to the members of the crotonase superfamily and contains an N-terminal α/β spiral core domain and a C-terminal α-helical region. Further structural and mutational analysis identified two catalytic glutamate residues, which is the conserved feature of the enoyl-CoA hydratases/dehydratases. A putative substrate-binding pocket was unveiled and the key roles of the residues implicated in substrate binding were verified by mutational analysis. The binding of the REC domain may lock RpfF in an inactive conformation by blocking the entrance of substrate binding pocket, thereby negatively regulating DSF production. These findings provide a structural model for the RpfC-RpfF interaction-mediated QS autoinduction mechanism. [ABSTRACT FROM AUTHOR]

Abstract: One cultivar and five experimental lines of Maryland-grown soybeans with improved fatty acid profiles were investigated for their phytochemical and antioxidant properties. Soybean oils were extracted and analyzed for their fatty acid profiles, tocopherols, and carotenoids. Two of the experimental lines were low in α-linolenic acid and another one was low in both α-linolenic and total saturated fatty acids. The defatted flours were extracted in 50% acetone and 70% ethanol, and estimated for isoflavone compositions, total phenolic contents (TPC), and scavenging capacities against peroxyl (ORAC), hydroxyl (HOSC), and 2,2-diphenyl-1-picryhydrazyl (DPPH) radicals. No difference was observed in tocopherols, carotenoids, TPC, and antioxidant properties between soybeans with reduced α-linolenic and/or saturated fats and the ones with ‘normal’ fatty acid profiles. This study indicates the possibility to produce soybeans with reduced linolenic and/or saturated fat and with desirable levels of health beneficial phytochemicals and antioxidant properties. [Copyright &y& Elsevier]

Abstract: Psyllium husks were treated with different concentrations of HCl in ethanol at ambient temperature to improve their gelling and water uptake properties. The acid-treated psyllium samples were examined and compared to the control, which was subjected to the same procedure without acid treatment, for their gelling properties, water uptake capacities, swelling volumes, and bile acid-binding capacities. The results showed that 0.36–1.44% HCl treatment in ethanol may significantly decrease the gelling, water uptake, and swelling capacities of psyllium without reducing their bile acid-binding abilities. Scanning electron microscopic (SEM) analysis showed that HCl treatment might reduce surface area of psyllium particle, which might contribute to their reduced water uptake capacity. The results from this study suggest that low concentration acid treatment in ethanol may improve psyllium functionality. [Copyright &y& Elsevier]

Ethnopharmacological relevance The spikes of Prunella vulgaris have long been used as a traditional Chinese medicine to treat various inflammation-related diseases. The aim of this study was to isolate and characterize homogenous polysaccharides from this herb and to evaluate their anticomplement activity. Materials and methods Anticomplement activity-guided fractionation of the hot water extract of P. vulgaris was performed by DEAE-cellulose and size-exclusion chromatography, yielding two homogeneous polysaccharides PW-PS1 and PW-PS2. The homogeneity, molecular weight, monosaccharide composition and linkage of the two polysaccharides were determined in addition to other chemical characterizations. The anticomplement activity of the polysaccharides was evaluated and expressed as 50% hemolytic inhibition concentration through the classical pathway (CH 50 value) and alternative pathway (AP 50 value). The preliminary mechanism for the complement activation cascade was also assessed. Results PW-PS1 and PW-PS2 were both branched acidic polysaccharides. PW-PS1 was composed of Ara, Xyl, and 4-methoxy-Glc A in a ratio of 1.0: 2.6: 0.8. The main linkages of the sugar residues of PW-PS1 included terminal β- d -Xyl p , 1,4-linked β- d -Xyl p , 1,3-linked α- d -Ara p , 1,3,5-linked α- d -Ara p , and terminal 4-methoxy-α- d -Glc p A. PW-PS2 was composed of Rha, Ara, Xyl, Gal, and Gal A in a ratio of 0.6: 1.0: 1.3: 1.8: 3.4. The main linkages between the sugar residues of PW-PS2 included terminal Ara f , 1,4-linked β- d -Xyl p , 1,3-linked α- d -Rha p , terminal α- d -Gal p , and 1,4,6-linked α- d -Gal p . PW-PS1 and PW-PS2 inhibited complement activation through both the classical and alternative pathways with CH 50 values of 0.28 and 0.13 mg/mL, respectively, and AP 50 values of 0.40 and 0.35 mg/mL, respectively. Preliminary mechanism studies using complement component-depleted sera showed that PW-PS1 acted on the C1q, C3, and C9 components and that PW-PS2 acted on the C1q, C2, C3, C5, and C9 components. Conclusion Our study suggested that PW-PS1 and PW-PS2 could be valuable for the treatment of diseases associated with the excessive activation of the complement system. [ABSTRACT FROM AUTHOR]

Two new pterocarpan glycosides ( 1 – 2 ), five new triterpenoids ( 3 – 7 ), and 13 known analogues ( 14 – 20 ) were isolated from the whole plants of Gueldenstaedtia verna . These new compounds ( 1 – 7 ) were elucidated by extensive spectroscopic techniques including 1D ( 1 H and 13 C) and 2D NMR experiments (COSY, HSQC, HMBC and NOESY), HR-ESI-MS and chemical methods. The absolute configuration of 1 was established by the optical rotation, the comparison of experimental and calculated electronic circular dichroism (ECD) spectra and an X-ray diffraction analysis. All the isolates were evaluated for their cytotoxicities against four human cancer cell lines and inhibitory activities on LPS-induced NO production in RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Abstract: A new meroterpene, psoracorylifol F (1), was isolated from Psoralea corylifolia fruits, along with two known meroterpenes (2 and 3), guided by TLC bioautography against O2 − radicals. The structure of 1 was elucidated by means of NMR, HRESIMS, and X-ray crystallographic analysis. All the three metroterpenes possessed potential inhibitory activity against LPS-induced NO production in RAW 264.7 cells with IC50 values ranging from 7.71 to 27.63μM. [Copyright &y& Elsevier]

Abstract: An ultra performance liquid chromatography–mass spectrometric (UPLC–MS) method was developed to investigate the pharmacokinetic properties of isorhamnetin, kaempferol and quercetin from a total flavone extract of Hippophae rhamnoides L. (TFH) after single dose oral administration. Rat plasma samples were pretreated using liquid–liquid extraction, and chromatographic separation was performed on a C18 column using a linear gradient of methanol and formic acid (0.1%). The pharmacokinetic parameters of isorhamnetin, kaempferol and quercetin from TFH in rats were quantitatively determined by UPLC with photodiode array detection (PDA). The qualitative detection of the three flavones was accomplished by selected ion monitoring in negative ion mode ESI-MS. Results of the pharmacokinetic study indicate that the three flavones in TFH were absorbed by passive diffusion in rats, and no “double-peak” phenomenon was observed in C-t curves of the three flavones from TFH except for quercetin. Results of this study indicate that the pharmacokinetic behaviors of isorhamnetin, kaempferol and quercetin when administered together in a complex herbal extract might be different than the individual behaviors of the same compounds administered in their pure forms. Results of this study also demonstrate that UPLC–MS is a rapid and practical method to determine the pharmacokinetic parameters of flavones present in an herbal extract. [ABSTRACT FROM AUTHOR]

Summary: Poly(A)-specific ribonuclease (PARN) is a homodimeric, processive, and cap-interacting 3′ exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. The crystal structure of a C-terminally truncated PARN in complex with m7GpppG reveals that, in one subunit, m7GpppG binds to a cavity formed by the RRM domain and the nuclease domain, whereas in the other subunit, it binds almost exclusively to the RRM domain. Importantly, our structural and competition data show that the cap-binding site overlaps with the active site in the nuclease domain. Mutational analysis demonstrates that residues involved in m7G recognition are crucial for cap-stimulated deadenylation activity, and those involved in both cap and poly(A) binding are important for catalysis. A modeled PARN, which shows that the RRM domain from one subunit and the R3H domain from the other subunit enclose the active site, provides a structural foundation for further studies to elucidate the mechanism of PARN-mediated deadenylation. [Copyright &y& Elsevier]

Abstract: In this paper, new sustained release microspheres with a surface coating of targeting moieties coating are presented. Bovine serum albumin (BSA) was used to prepare the microspheres loading with 5-fluorouracil (5-FU) by means of chemical crosslinking method and then the microspheres were coated with N-galactosylated chitosan by electrostatic interaction. The structure of coating layers on the surface of 5-FU-loaded BSA microspheres was characterized by attenuated total reflection Fourier (ATR-FTIR), electron spectroscopy for chemical analysis (ESCA), wide X-ray diffraction (WXRD) and transmission electron microscopy (TEM). The properties of the coated microspheres containing 5-FU were determined. The size was in the range of 0.60–0.65μm, zeta potential was 16.6mv, and the encapsulation efficiency, drug loading, and the content of galactosyl groups were 40.3% (w/w), 2.9% (w/w), and 5.4% (w/w), respectively. In comparison with uncoated microspheres, the coated microspheres showed delayed release and less burst release in vitro. All results suggested the BSA microspheres preparation with galactosyl chitosan coating could be a promising method for targeted delivery to the liver. [Copyright &y& Elsevier]

Three undescribed seco -ursane stereoisomers, ilexcornutosides A – C, two undescribed triterpenoid saponins, ilexcornutosides D – E, and 11 known triterpenoids were isolated from the leaves of Ilex cornuta Lindl. & Paxton. Ilexcornutosides A – C and F with the same planar structures are unique 13(18)-ene-18,19- seco -ursane skeleton triterpenoids, identified as (3 S ,12 R)-3- O - β - d -glucopyranosyl-(1 → 2)- α - l -arabinopyranosyl]-12-hydroxyl-19-oxo-18,19-secours-13(18)-en-28,21-lactone. Among them, ilexcornutosides A and F (or ilexcornutosides B and C) are a pair of diastereomers at the C-20 position; ilexcornutosides A and C (or ilexcornutosides B and F) are a pair of diastereomers with epimerization at the C-21. Their structures were established by extensive spectroscopic (IR, 1D and 2D NMR, and HR-ESI-MS) and chemical analyses. The absolute configurations of ilexcornutosides A, B, D and F were determined by a single crystal X-ray diffraction analysis with a Cu Kα radiation. The inhibitory effect of ilexcornutosides A – F on the PPARγ expression was assessed in the 3T3-L1-Lenti- PPARγ -Luc cells using a single luciferase reporter assay. Ilexcornutosides A and C showed a comparable activity in decrease of the PPARγ expression to the positive control (T0070907) at 5 μ M. Image 1 • Sixteen triterpenoids were isolated and identified from leaves of Ilex cornuta , a herb with the benefit of weight loss. • Four unique 13(18)-ene-18,19- seco -ursanes were identified by spectroscopic and single crystal X-ray diffraction analysis. • Seven triterpenoids showed anti-adipogenic activity via inhibition of the PPARγ expressions in 3T3-L1 preadipocytes at 5 μ M. [ABSTRACT FROM AUTHOR]

Laser cladding process consolidates powder or wire materials into a dense metal part with the assistance of laser energy source. Simulation of temperature distribution and fluid flow of the laser cladding process was carried out using the finite volume method (FVM). The influence of the Marangoni convection on the dimensions of the melt pool was investigated. A double peak phenomenon of flow velocity on the surface of the molten pool was induced by the Marangoni convection. The heat and mass transfer in the molten pool caused by the Marangoni effect was measured by the Peclet number. Temperature gradient (G) and solidification rate (S) were calculated to predict the morphology and size of the solidification microstructures. During the solidification process of the molten pool, the cooling rate (G×S) declines from the top region of the cladding layer, and the solidification rate of the cladding layer gradually decreases from the top to the bottom. The corresponding microstructure is in a good agreement with the experimental results. The metallurgy bonding between the substrate and the cladding layer is not very well when the simulated molten pool depth is smaller than the thickness of the pre-placed powder bed. [ABSTRACT FROM AUTHOR]