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Fibroblast-like synoviocytes (FLS) obtained from the joint synovium of rheumatoid arthritis (RA) patients exhibit hyperplasia and aggressive inflammatory phenotypes. This study was designed to explore the anti-inflammatory mechanism of IL-6R inhibitor, tocilizumab, in FLS-mediated inflammation in RA from the perspective of non-coding RNAs (ncRNAs). To this end, we sorted primary FLS obtained from the synovium of patients with RA and cultured them in vitro. The cells were then treated with tocilizumab and subjected to lncRNA- and miRNA-seq to identify the ncRNAs regulated by tocilizumab treatment using bioinformatic analysis and experimental verification. Tocilizumab treatment enhanced the expression of lncRNA MIR31HG and reduced that of micoRNA-214 (miR-214). In addition, miR-214 activated the AKT signaling pathway by directly targeting MIR31HG and PTEN. In addition, the tocilizumab-MIR31HG-miR-214-PTEN-AKT axis regulated the proliferation, migration, and production of inflammatory molecules and matrix metalloproteinases (MMPs) in RA-FLS. Furthermore, co-culture experiments showed that this axis could inhibit the inflammatory phenotype of macrophages and protect chondrocytes. In summary, our study shows that tocilizumab suppresses RA-FLS inflammation by regulating the MIR31HG-miR-214-PTEN-AKT pathway, and presents new insights on RA pathogenesis and potential targets for RA therapy.

Solution-processed organic light-emitting diodes (OLEDs) are much preferred for the manufacture of low-temperature, low-cost, large-area, and flexible lighting and displaying devices. However, these devices with high external quantum efficiency are still limited, especially for blue ones. In addition, the molecular configurations of emitters are usually complicated, indicative of high costs. In this study, two simple-structured thermally activated delayed fluorescent emitters M1 and its polymer P1 were synthesized with acridine as a donor and benzophenone as an acceptor. Solution-processed OLEDs were prepared based on M1 and P1 as doped light-emitting layer, and M1-based doped device could achieve maximum external quantum efficiency of up to 20.6% with blue-light emission.

Graphene (G) and its derivatives are important nanomaterials with potential medical applications for biosensors and implanting biomaterials. The hydrophobicity and surface microstructures of substrates have great influences on the biological and physical properties of the surface-bound cells. In this work, we used the two-beam laser interference (TBLI) technique to prepare a two-dimensional (2-D) grating structure on the surface of graphene oxide (GO) film. We investigated the effect of GO and the GO film with the 2-D grating structure substrates on the growth behavior of rat brain microvascular endothelial (bEnd.3) cells. The results demonstrated that the cell spreading area and the number of surface-bound cells were closely related to the hydrophobicity of the substrate and the presence of oxygen-containing functional groups (OCGs). Due to the interaction of laser and GO, the GO in the interference area was transformed into reduced graphene oxide (RGO). The grating-structured GO film significantly affected the direction of cell spreading and morphology. It has a good application prospect as a scaffold in tissue engineering, and promising applications in the fields that require highly directional growth of cells, such as nerve injury repair, tendon repair and regeneration.

Materials exhibiting thermally activated delayed fluorescence (TADF) have been extensively explored in the last decade. These emitters have great potential of being used in organic light-emitting diodes because they allow for high quantum efficiencies by utilizing triplet states via reverse intersystem crossing. In small molecules, this is done by spatially separating the highest occupied molecular orbital from the lowest unoccupied molecular orbital, forming an intramolecular charge-transfer (iCT) state and leading to a small energy difference between lowest excited singlet and triplet states (ΔEST). However, in polymer emitters, this is harder to achieve, and typical strategies usually include adding known TADF units as sidechains onto a polymer backbone. In a previous work, we proposed an alternative way to achieve a TADF polymer by repeating a non-TADF unit, polymerizing it via electron-donating carbazole moieties. The extended conjugation on the backbone reduced the ΔEST and allowed for an efficient TADF polymer. In this work, we present a more in-depth study of the shift from a non-TADF monomer to TADF oligomers. The monomer shows non-TADF emission, and we find the delayed emission to be of triplet-triplet annihilation origin. An iCT state is formed already in the dimer, leading to a much more efficient TADF emission. This is confirmed by an almost two-fold increase of photoluminescence quantum yield, a decrease in the delayed luminescence lifetime, and the respective spectral lineshapes of the molecules.

Molybdenum disulfide (MoS2) has received enormous attentions in the electrochemical energy storage due to its unique two-dimensional layered structure and relatively high reversible capacity. However, the application of MoS2 in potassium-ion batteries (PIBs) is restricted by poor rate capability and cyclability, which are associated with the sluggish reaction kinetics and the huge volume expansion during K+ intercalation. Herein, we propose a two-dimensional (2D) space confined strategy to construct van der Waals heterostructure for superior PIB anode, in which the MoS2 nanosheets can be well dispersed on reduced graphene oxide nanosheets by leveraging the confinement effect within the graphene layers and amorphous carbon. The strong synergistic effects in 2D van der Waals heterostructure can extremely promote the electron transportation and ions diffusion during K+ insertion/extraction. More significantly, the 2D space-confinement effect and van der Waals force inhibit polysulfide conversion product dissolution into the electrolyte, which significantly strengthens the structural durability during the long-term cycling process. As anticipated, the as-synthesized the “face-to-face” C/MoS2/G anode delivers remarkable K-storage performance, especially for high reversible capacity (362.5 mAh·g−1 at 0.1 A·g−1), excellent rate capability (195.4 mAh·g−1 at 10 Ag−1) and superior ultrahigh-rate long-cycling stability (126.4 mAh·g−1 after 4000 cycles at high rate of 5 A·g−1). This work presents a promise strategy of structure designing and composition optimization for 2D layered materials in advanced energy storage application.

By an in situ coupling-interrupted transfer hydrogenation strategy, we herein report, for the first time, a ruthenium/acid co-catalyzed reductive α-phosphinoylation of 1,8-naphthyridines with diarylphosphine oxides, which offers a direct construction of novel α-phosphinoyl 1,2,3,4-tetrahydronaphthyridines with the merits of broad substrate scope, good functional group tolerance, excellent regio- and chemoselectivity, and high step and atom-efficiency. The employed strategy is anticipated to be further utilized in developing direct transformations of inert N-heteroarenes into functional frameworks.

In this paper, a way to improve the temperature stability of DC conductivity and breakdown characteristics of polyethylene (PE) is proposed using a crosslinked linear low density polyethylene (LLDPE). The ratio of DC conductivity, as well as breakdown strength values under 90 to 30°C is used to determine the temperature stability of DC properties. The closer it is to 1, the better the performance of temperature stability. The results show that when using crosslinked-LLDPE material, the ratio of DC conductivity under 90 to 30°C is 10.5, while it is 461.6 for crosslinked-LDPE samples with the same DCP content. And the ratio of DC breakdown strength is 0.97 for crosslinked-LLDPE, while it is 0.32 for crosslinked-LDPE. The gel permeation chromatography (GPC) method, hot-set test, differential scanning calorimetry (DSC) analysis and scanning electron microscopy (SEM) images show that the fine arrangement and smaller molecular weight between crosslinks of molecular and morphology structure that LLDPE owns contribute to the improvement in comparison with LDPE. The findings may contribute a solution to the development of HVDC power cable insulation materials.

Structure control is widely admitted as a feasible strategy to restrain volume change and enhance electrical conductivity for chalcogenide anode materials. Herein, three-dimensionally hierarchical structure Co0.85Se@N-doped graphene hybrid is well-designed and synthesized by a facile hydrothermal strategy and post-calcination. It is noted that, owing to the nanoscale Kirkendall effect, the Co0.85Se nanograins derived from uniform zeolitic imidazolate framework (ZIF-67) precursor are incorporated into a polyhedron-in-polyhedron structure, which is consisted of in-situ formed amorphous carbon and interconnected pliable graphene nanosheets with enormous N-doping atoms. This unique dual-carbon protecting layers are beneficial to mitigate the volume expansion with high integrity, and facilitate the fast Li/electron transport with improved conductivity simultaneously, thus resulting in the superior Li-storage performance. As expected, the framework-controlled Co0.85Se@N-doped rGO composite demonstrates an outstanding cycling stability (787.7 mA h g−1 after 1000 cycles at 2 A g−1) and remarkable rate capability (400.8 mA h g−1 at ultrahigh rate of 10 A g−1). This work presents an enlightened strategy to design chalcogenide anode with desired nano-/microstructure by structure control and kinetic increase.

Kadsura heteroclita Roxb. Craib. (Schisandraceae), is a vine plant mainly distributed in southwest part of China. A new dibenzocyclooctadiene lignan, kadsulignan W (1), along with eleven known lignans (2-12) were isolated from chloroform soluble fraction of stems of Kadsura heteroclita. The structure of new lignan was elucidated by extensive spectroscopic techniques, namely one- and two-dimensional NMR spectroscopy, and HRESI-MS analysis. The absolute configuration of the biphenyl ring in the new dibenzocyclooctadiene lignan was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated on human isolated neutrophils, and compounds 5, 8, 9, and 10 were found to be strongly active with the IC50 of 36.68, 34.41, 35.97, and 33.65 µM, respectively. Furthermore, compound 8 was also found to be cytotoxic against human gastric cancer cells (BGC 823), and human cervical cancer cell lines (HeLa) with the IC50 values of 11.0, and 23.8 µM, respectively.

Herein, we present a ruthenium-catalyzed new hydrogen evolution ortho-aminoalkylation of phenolic derivatives with cyclic amines as the coupling agents. The developed cross-coupling reaction offers a practical platform for direct access to a variety of functionalized phenols with the features of good substrate and functional group compatibility, readily available catalyst system and feedstocks, no need for additional sacrificial oxidants, and high atom efficiency.

Objective To study the antipyretic and anti-inflammatory constituents from the active fraction of Reduning (RDN) Injection. Methods In this study, the active fraction of RDN Injection was screened by the LPS-induced mouse endotoxin shock model. The chemical constituents were isolated by chromatography on HP-20 macroporous adsorptive resins, silica gel, ODS columns and reverse phase MPLC and HPLC repeatedly, and their structures were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, ECD) and chemical methods. Meanwhile, we evaluated the anti-inflammatory activities of the isolates by measuring their inhibitory effects on TNF-α production in LPS stimulated RAW 264.7 macrophages. Results The 95% ethanol eluate of RDN Injection by the macroporous adsorption resin column was proved to be the antipyretic and anti-inflammatory active fraction of this injection. A novel iridoid, named jasminoide A (1), and a new guaiane sesquiterpenoid, named (1R,7R,8S,10R)-7,8,11-trihydroxy-4-guaien-3-one (2), were isolated from Reduning injection, and compound 2 can inhibit TNF-α production with IC50 values of 72.24 µmol/L. Conclusion In this study, two new terpenoids were isolated from Reduning Injection, and compound 2 showed inhibitory activity against LPS-activated TNF-α production in RAW 264.7 cells in vitro.

A Gram-stain-positive, aerobic actinomycete, designated strain BMP B8144T, was isolated from desert soil, in Xinjiang province, northwest China. The isolate produced scanty aerial mycelium and fragmented substrate mycelium on most tested media. Cell-wall hydrolysates contained meso-diaminopimelic acid, galactose and mannose. The diagnostic phospholipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylhydroxylethanolamine, phosphatidylinositol, and phosphatidylinositol mannosides. The major fatty acids included iso-C16 : 0, C17 : 1 ω8c and iso-C15 : 0. The predominant menaquinones were MK-9(H4) and MK-10(H4). The DNA G+C content was 70.4 mol% (genome). Based on the 16S rRNA gene sequence analysis on EzBioCloud server, strain BMP B8144T showed the closest similarities to Saccharothrix lopnurensis YIM LPA2hT (98.9 %) and ‘ Saccharothrix yanglingensis ’ Hhs.015 (98.6 %). However, it can be distinguished from the closest strains based on the low levels of DNA–DNA relatedness (59.3±1.8 and 47.9±2.3 %, respectively). A combination of morphological, chemotaxonomic and phylogenetic characteristics, strain BMP B8144T represents a novel species of the genus Saccharothrix , for which the name Saccharothrix deserti sp. nov. is proposed. The type strain is BMP B8144T (=CGMCC 4.7490T=KCTC 49001T).

Three luminogens were designed and synthesized by integrating TPE with hole-transporting carbazole (Cz) and/or electron-transporting 1,2-diphenyl-1H-benzimidazole (PBi), and bare tetraphenylethene and another donor–acceptor (D–A) compound with aggregation-caused quenching (ACQ) were also prepared for comparison. In nondoped OLEDs, the best one with both aggregation-induced emission (AIE) properties and donor–acceptor (D–A) structures showed excellent performances with Lmax, CEmax, PEmax, and EQEmax of 24 308 cd m−2, and 15.10 cd A−1, 14.82 lm W−1, and 5.34%, respectively, which reached the theoretical limit of fluorescent OLEDs.

Spodoptera frugiperda is a serious threat to global food production. Our previous study demonstrated that Camptothecin (CPT), a bioactive secondary metabolite from Camptotheca acuminata (Decne: Nyssaceae), exhibits adverse impact on the larval midgut of S. frugiperda and inhibits insect growth. However, effects of CPT on fat bodies of S. frugiperda larvae have not been examined yet. In the present study, we found that histological structures of fat bodies of S. frugiperda larvae were damaged in insects treated with CPT. Comparative transcriptomic analyses among different fat body samples from controls and insects treated with 1.0 and 5.0 μg/g CPT were performed. A total of 4212 and 5044 differentially expressed genes (DEGs) were identified in the samples treated with 1.0 and 5.0 μg/g CPT, respectively. Our data indicated that the pathways of detoxification, immune response, fatty acids, chitin, and hormone biosynthesis in fat bodies were affected by CPT treatments based on DEGs. These results provided a comprehensive view of the damage and gene expression changes in fat bodies of S. frugiperda after CPT exposure, which shall be useful to reveal the mechanism of CPT toxicity against S. frugiperda in future.

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.

Phonon-assisted excitation energy transfer between detuned pigments in photosynthetic system has been identified as a potential design principle for optimizing exciton migration on next-generation materials. Based on a detuned dimer system consisting of a donor and an acceptor modeled by two two-level systems with different excitation energy, in which one of them is coupled to a high-energy vibrational mode and driven by a Gaussian-type pulse, we show the important role of the high-energy vibrational mode on both energy absorption and transfer in the detuned dimer model. It is found that, for driven pulse with fixed width, the efficiency of energy absorption and transfer varies with the parameters of the high-energy vibrational mode in different patterns, but there exist optimal parameters for both energy absorption and transfer. In addition, the narrower the width of the driven pulse is, the higher both the efficiency of energy absorption and transfer are.

Charge transfer (CT) dynamics across metal-molecule interfaces has important implications for performance and function of molecular electronic devices. CT times, on the order of femtoseconds, can be precisely measured using synchrotron-based core-hole clock (CHC) spectroscopy, but little is known about the impact on CT times of the metal work function and the bond dipole created by metals and the anchoring group. To address this, here we measure CT dynamics across self-assembled monolayers bound by thiolate anchoring groups to Ag, Au, and Pt. The molecules have a terminal ferrocene (Fc) group connected by varying numbers of methylene units to a diphenylacetylene (DPA) wire. CT times measured using CHC with resonant photoemission spectroscopy (RPES) show that conjugated DPA wires conduct electricity faster than aliphatic carbon wires of a similar length. Shorter methylene connectors exhibit increased conjugation between Fc and DPA, facilitating CT by providing greater orbital mixing. We find nearly 10-fold increase in the CT time on Pt compared to Ag due to a larger bond dipole generated by partial electron transfer from the metal-sulfur bond to the carbon-sulfur bond, which creates an electrostatic field that impedes CT from the molecules. By fitting the RPES signal, we distinguish electrons coming from the Fe center and from cyclopentadienyl (Cp) rings. The latter shows faster CT rates because of the delocalized Cp orbitals. Our study demonstrates the fine tuning of CT rates across junctions by careful engineering of several parts of the molecule and the molecule-metal interface.

Despite the widespread applications of 2-(hetero)aryl N-heteroarenes in numerous fields of science and technology, universal access to such compounds is hampered due to the lack of a general method for their synthesis. Herein, by a H2O-mediated H2-evolution cross-coupling strategy, we report an iridium(III)-catalyzed facile method to direct α-arylation of N-heteroarenes with both aryl and heteroaryl boronic acids, proceeding with broad substrate scope and excellent functional compatibility, oxidant and reductant-free conditions, operational simplicity, easy scalability, and no need for prefunctionalization of N-heteroarenes. This method is applicable for structural modification of biomedical molecules, and offers a practical route for direct access to 2-(hetero)aryl N-heteroarenes, a class of potential cyclometalated C^N ligands and N^N bidentate ligands that are difficult to prepare with the existing α-C-H arylation methods, thus filling an important gap in the capabilities of synthetic organic chemistry., 2-(hetero)aryl N-heteroarenes are ubiquitously applied in numerous fields of science and useful for the development of bioactive molecules and drugs, but there is a lack of general methods for their synthesis. Here, the authors report an iridium(III)-catalyzed method for direct α-arylation of N-heteroarenes with aryl and heteroaryl boronic acids, by a H2O-mediated H2-evolution cross-coupling strategy.

Due to their ultra-high theoretical capacity and low discharge potential, rich Sn-based materials are considered promising candidates for lithium ion battery (LIB) anodes; however, the development of SnOx electrodes is restricted by their low conductivity and severe volume change during repeated cycling. In this study, carbon matrix encapsulating heterostructured SnOx ultrafine nanoparticles (SnOx@C/rGO) were synthesized in situ through a facile solvent mixing, followed by thermal calcination. During the decomposition of the Sn-organic precursor, the sizes of the as-prepared SnOx nanoparticles were strictly controlled to 5–10 nm; they were intimately wrapped by the in-situ formation of ultrathin carbon layers, which prevented the agglomeration of nanograins. Furthermore, the SnOx@C nanoparticles were evenly anchored on the surface of reduced graphene oxide (rGO) to construct a highly conductive carbon framework. It is notable that the carbon matrix prepared in situ can accommodate the volumetric change of SnOx and facilitate the transport of Li+ ions during continuous cycling. Benefiting from the synergistic effect between the SnOx nanoparticles and carbon matrix prepared in situ, the heterostructured SnOx@C/rGO will confer improved structural stability and reaction kinetics for lithium storage. It delivers a stable reversible discharge capacity of 1092.2 mAh g−1 at a current rate of 0.1 A g−1, and enhanced cycling retention with a capacity of 447.8 mAh g−1 after 1200 cycles at a current rate of 5.0 A g−1. This strategy provides a rational avenue to design oxide anodes with efficient hierarchical structure for LIB development.

Pulsatillae radix, a traditional Chinese medicine (TCM), is often used in combination with florfenicol for treatment of intestinal infection in Chinese veterinary clinics. Anemoside B4 (AB4) is the major effective saponin in Pulsatillae radix. This study aimed to investigate whether the pharmacokinetics of florfenicol in broilers was affected by the combination of AB4. In this study, broilers were given AB4 (50 mg/kg BW), or 0.9% sodium chloride solution by oral administration for 7 days. They were then fed florfenicol orally (30 mg/kg BW) on the eighth day. The results showed that the AUC(0-∞), MRT(0-∞), t1/2z and Cmax of florfenicol were significantly decreased, and the Vz/F and CLz/F were significantly increased by AB4; the mRNA expression levels of CXR, CYP3A37 and MDR1 (except CXR and CYP3A37 in the liver) were up-regulated by AB4. In conclusion, AB4 altered the pharmacokinetics of florfenicol, resulting in lower plasma concentrations of florfenicol, this was probably related to the mRNA expression of CXR, CYP3A37 and MDR1 in the jejunum and liver (except CXR and CYP3A37) increased by AB4. The implications of these findings on the effect of traditional Chinese medicine containing AB4 on the effectiveness of florfenicol in veterinary practice deserve study.

It is already known that bisphenol S (BPS) has been used as a substitute for BPA in thermal papers in recent years. It is not clear, however, if BPS has also been used to replace BPA in can coatings as currently being speculated due to a lack of credible studies on migration of BPS from can coatings and occurrence data of BPS in foods. In this study, an LC-MS/MS method was developed for the analysis of BPS, along with several other bisphenols, and method detection limits for BPS varied from 0.0017 to 3.1 ng/g depending on the type of sample matrix and the amount of sample analysed. This method was used to analyse 159 different food composite samples from a recent Canadian total diet study. Bisphenol E (BPE), bisphenol B (BPB), and bisphenol AF (BPAF) were not detected in any of the 159 food composite samples, bisphenol F (BPF) was detected in only three samples (25-2360 ng/g), and bisphenol A (BPA) was detected in 10 samples (5.3-41 ng/g) which were all prepared from canned foods. BPS was not detected in any of the canned food composite samples but was detected in nine food composite samples prepared from meat and meat products (1.2-35 ng/g), indicating sources for BPS other than can coatings may be possible, which will be investigated in future studies.

Background There is a lack of information on the presence of volatile organic compounds including p-cymene in foods for dietary exposure assessment. p-Cymene is a monoterpene found in many plant species, which has been used as a flavouring agent in foods and also exhibits antioxidant and antimicrobial properties. While the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has no safety concerns at current levels of intake when used as a flavouring, the current study examines p-cymene levels in foods in general, not just from possible uses as a flavouring, as there could still be a potential health concern if there were high levels of exposure. Results 159 food composite samples from the 2014 Canadian Total Diet Study were analysed for p-cymene using a gas chromatographic-mass spectrometric method after headspace solid-phase microextraction. Concentrations of p-cymene in the composite samples of most food types were generally low, with a maximum level of 73.5 μg g-1 , detected in the composite sample of herbs and spices. Dietary exposures to p-cymene were estimated for different age groups of Canadian populations. Conclusions Although p-cymene was detected in various foods, estimated dietary exposures to p-cymene for different age groups are well below the human intake threshold of toxicological concern established by JECFA of 1800 μg per person per day for structural class I flavours, which includes p-cymene. © 2019 Society of Chemical Industry.

Methylmercury (MeHg) is a widespread pollutant in aquatic ecosystems, but its toxicity to the early life stages of marine fish has not been adequately investigated. This study used acute toxicity tests on embryonic-larval stages of a marine flounder Paralichthys olivaceus to determine the LC50 values for embryos and larvae and evaluate the responses of several biological endpoints to subacute MeHg exposure. Under exposures (0–15 μg L−1) below LC50 values (

The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloids (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds.

Three novel bisbenzimidazole derivatives have been synthesized and developed as dual-functional fluorescent sensors for the rapid and highly selective detection of Ag+ and Fe3+ ions in semi-aqueous medium with distinct spectral response for the first time. The absorption intensity is drastically decreased after the addition of Ag+. Contrarily, it is markedly increased upon the addition of Fe3+. And there is a good linear relation at low concentration of both Ag+ and Fe3+, which provides a quantitative method for their detection. Similarly, the sensors show a distinct fluorescence response towards Ag+ and Fe3+ with a different fluorescence color change under UV light. In addition, no significant changes and interference can be observed with other metal ions. The sensing mechanism studies confirm that the N atom in CN of benzimidazole ring of sensor 4a may bind with Ag+ or Fe3+ ion to form metal complex. And there is only a static quenching process for the 4-Ag+ complex system, but both dynamic and static quenching processes occur in the 4-Fe3+ complex system. Moreover, sensors 4 can steadily work in solution with a wide range of pH 4-13 and rapidly respond to Ag+ and Fe3+ with a response time of 10 s. Finally, the sensors have been successfully applied to the visual detection of Ag+ and Fe3+ not only in solution, but also in test paper.

Herein, the MoP@C nanocomposite was successfully fabricated via a facile sol–gel approach followed by an annealing process, which demonstrated excellent electrochemical properties as a novel anode for sodium storage. The addition of the surfactant Tween 80 led to the formation of strong P–C bonds, ensuring in situ formation of a thin carbon layer on the nanosized MoP particles, which could mitigate particle aggregation and maintain the stable framework. Moreover, owing to the synergistic effect between the MoP nanoparticles and the highly conductive carbon network, the MoP@C nanocomposite delivered high reversible capacity and a superior cyclability (maintaining 180.3 mA h g−1 after 250 cycles at 500 mA g−1). In addition, the sodium-storage mechanism of MoP was unraveled by the combined analyses of in situ X-ray diffraction and ex situ transmission electron microscopy, confirming an incomplete conversion reaction during the sodiation/desodiation process; this provided an insight into the structural evolution and Na+-ion storage performance of phosphide anodes.

Taking advantage of synergistic effects, the ternary metal oxides have attracted tremendous interest. Herein, ZnMn2O4 nano-particles have been fabricated via a facile one-step approach at room temperature, that of simply mixing ZnO and MnO in KOH aqueous solution without templates. When used as an anode for lithium ion batteries, it delivers the excellent structure stability (1028.9 mA h g−1 at 1.0 A g−1 after 400 cycles). Surprisingly, the low-cost and eco-friendly route provides a novel strategy to synthesize the mixed transition metal oxide electrodes with readily scaled-up production.

Bimetallic sulfides deliver redox reactions and provide a buffer effect during electrochemical reactions, and thus have been the focus of research in the field of energy storage materials. Herein, a carbon cage coated bimetallic sulfide (Fe2Zn3S5/Fe1−xS@C) composite with a heterogeneous structure was synthesized by using a metal–organic framework (FeIII-MOF-5) as a self-sacrificial template. The composite nanoparticles were monodispersed and encapsulated in a carbon cage. This setup ensured excellent performance by improving electrical conductivity and preventing the dissolution of polysulfide intermediates. In situ X-ray diffraction (In situ XRD) and cyclic voltammetry (CV) test results indicate that conversion reactions occur during charging and discharging processes. When tested in coin cells, the composite material exhibited excellent cycling and rate performances, demonstrating high reversible capacities of 2071.2 mA h g−1 at a current density of 500 mA g−1 after 700 cycles and 736.1 mA h g−1 at a current density of 5000 mA g−1 after 700 cycles. The results indicate that the composite derived from FeIII-MOF-5 is a promising high-performance anode material for lithium-ion batteries.

Phthalates are a group of diesters of ortho-phthalic acid. Diesters of para-phthalic acid and meta-phthalic acid are also produced, but they are not the phthalates that are commonly referred to in the literature. The applications of phthalates in products vary depending on the molecular weights of the phthalate selected, with higher molecular weight phthalates being primarily used as plasticizers to soften polyvinyl chloride (PVC) products, and lower molecular weight phthalates as solvents to hold colour and scent in various cosmetics and personal care products. Some phthalates are also used in food contact materials and can migrate from food contact materials into foods, especially fatty foods, since they are not chemically bound to the polymer. Although structurally di-(2-ethylhexyl) adipate (DEHA) is different from the phthalates, phthalates and DEHA are both lipophilic and thus have been analysed together in some studies to investigate their occurrence in foods. Like phthalates, DEHA is also widely used as a plasticizer in food contact materials, such as PVC food wrapping or cling films, and PVC gaskets of lids for glass jars. Like other plasticizers, DEHA is not chemically bound to the polymer and can also migrate from food contact materials to foods. Dairy foods are a type of foods produced from or containing milk, and they are an important food group among the foods consumed by all population, especially children. Due to their large octanol–water partition coefficient (KOW) values or high fat solubility, phthalates and DEHA are found primarily in fat-containing foods, and thus, dairy foods have been among the important food groups for human exposure to phthalates and DEHA in various countries. This chapter provides an updated overview on the occurrence of DEHA and phthalates in foods, dairy foods in particular, and development and issues of the analytical methods since the last edition.

Jin-hong tablets (JHT), a well-known Traditional Chinese Patent Medicine (TCPM), has been effectively used for the treatment of chronic superficial gastritis (CSG) in clinic. The metabolic profile of TCPMs is the key part of discovering their bioactive components. In this study, a five-step strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and metabolynxTM software combined with mass defect filter (MDF) technique was developed to delineate the metabolic profile of JHT in vivo. As a result, a total of 163 JHT-related xenobiotics (38 prototypes and 125 metabolites) were identified or tentatively characterized in rat biological samples, and the phase I and II metabolism process mainly included demethylation, hydroxylation, sulfation and glucuronidation. In addition, after oral administration of JHT, a large amount of alkaloids-related ingredients were detected in rat plasma samples, indicating that alkaloids may play an important role in the treatment of CSG with JHT. This study is beneficial for understanding of JHT's in vivo metabolic profiles and characteristics, which helps to reveal its in vivo effective components and provides a solid basis for further studies on its functional mechanism.

With HVDC lines developing towards a higher voltage level and a larger transmission capacity, cables have been a crucial equipment subjected to both electrical and thermal stress. Polystyrene (PS) pinning crosslinked polyethylene (XLPE), a new type of insulating material, shows a great potential to fulfil the requirements of insulating materials for extruded HVDC cables. However, the role of pinning in the interphase area has not been fully understood. In this study, a series of dicumyl peroxide (DCP) contents were added, and DC dielectric properties including conductivity and breakdown strength were analysed. Results show that with the increase of DCP content, DC conductivities of samples tend to decrease from 30°C to 90°C and DC breakdown strengths are enhanced by ∼60% both at 70°C and 90°C. Based on polymer chain alignment model, it is considered that polymer chain alignment at the interfacial area between PS particles and the matrix is a major factor that leads to the enhancement of DC dielectric properties, and a higher pinning extent for samples does present better electric performances. This study may help to apply PS pinning XLPE to insulating materials for extruded HVDC cables.

Seawater acidification can cause threats to both calcifying and uncalcifying marine organisms, affecting their acid-base regulatory functions like immune system and biomineralization. Marine pollutants, such as cadmium (Cd) that is globally distributed in coastal ecosystems, do not affect organisms alone but commonly as combined stressors. To investigate the toxicological effects of Cd on the immune and biomineralization of marine fishes under seawater acidification, flounder Paralichthys olivaceus was exposed to seawater acidification (control (pH 8.10), 7.70 and 7.30) and Cd exposure (control (0.36 μg L−1), 0.01 and 0.15 mg L−1 Cd) for 49 days from embryonic stage until they became settled. Immune and biomineralization-related biomarkers of flounder at the end of exposure were investigated. Results showed that single seawater acidification and Cd exposure or combined exposure significantly affected the immune system-related enzyme activities. Specifically, lysozyme (LZM) activity was significantly inhibited by single seawater acidification and Cd exposure, indicating innate immunosuppression under two stressors. Contents of IgM, HSP70 and MT were induced by seawater acidification or Cd exposure, indicating a detoxification mechanism that responded to the stressors. The expressions of immune-related genes were upregulated (hsp70 and mt) or downregulated (lzm) under Cd exposure. Of the biomineralization-related enzymes, activities of carbonic anhydrase (CA), Na+/K+-ATPase and Ca2+-ATPase increased under seawater acidification and Cd exposure, a potential mechanism in response to changes of acid-base balance induced by the stressors. Generally, immune and biomineralization of the flounder responded more sensitively to Cd exposure than seawater acidification. Seawater acidification aggravated the toxicological effects of Cd exposure on the two physiological functions, while high Cd exposure augmented their responses to seawater acidification.

Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine (TCM) formula, has a good therapeutic effect on rheumatoid arthritis (RA) and is widely used in China. To comprehensively elucidate the therapeutic mechanism of QWTB in the treatment of RA, the effects of QWTB on biomarkers and metabolic pathways in a rat model of kidney deficiency arthritis were investigated in this study. The effects of QWTB on pharmacodynamic indicators, including paw swelling, arthritis score; interleukin-1β, interleukin-6, interleukin-17 F, tumor necrosis factor-α, tartrate-resistant acid phosphatase 5b, bone alkaline phosphatase, bone-specific alkaline phosphatase, bone glaprotein, urea, and creatinine levels; and histopathology, suggested that QWTB significantly improved renal function, inhibited the inflammatory response, and reduced bone loss. In total, 39 differential metabolites were screened by comparing the endogenous components between blank and model rat plasma, among which 16 metabolites were altered by QWTB. The metabolism pathway analysis revealed that α-linolenic acid metabolism, phenylalanine metabolism, sphingolipid metabolism, histidine metabolism and glycerophospholipid metabolism were greatly disturbed. Thus, the biomarkers investigated included (1) α-linolenic acid, (2) hippuric acid, (3) phosphatidylethanolamine (15:0/22:2(13Z,16Z)), (4) phenylpyruvic acid, (5) sphinganine, and (6) urocanic acid. QWTB affected three abnormal biomarkers: (3), (4), and (6). Phenylphruvic acid, sphinganine and urocanic acid were significantly associated with pharmacodynamic indicators, as shown by Pearson correlation analysis. These results indicated that RA-related biomarkers had certain reliability and biological significance. In summary, QWTB regulated the metabolic disorders in rats with RA. Its therapeutic mechanism may involve the regulation of phenylalanine metabolism, histidine metabolism, and glycerophospholipid metabolism. The results of this study are useful for understanding the therapeutic mechanisms of TCM.

Methylmercury (MeHg) is the most toxic form of mercury and can accumulate in the cells of marine organisms, such as fish, causing adverse effects on various physiological functions. This study examined MeHg accumulation and its toxicological role in antioxidant defenses in tissues, including the liver, gills, and muscle of flounder (Paralichthys olivaceus) juveniles. After 30 d of MeHg exposure (0, 0.1, 1.0, 10.0, and 20.0 µg L−1), the accumulation of MeHg in the three tissues correlated positively with the concentration of MeHg and exhibited tissue specificity in the order of liver > gills > muscle. Among the antioxidant markers, the activities of SOD (superoxide dismutase) and GST (glutathione S-transferase) as well as the content of glutathione (GSH) in the liver and gills were induced at 0.1–10.0 µg L−1 but repressed at 20.0 µg L−1. The activities of SOD and GST and the content of GSH in the muscle significantly increased with increasing MeHg concentration. Catalase (CAT) activity in the liver was induced at 0.1–1.0 µg L−1 but inhibited at 10.0–20.0 µg L−1, whereas exposure to MeHg did not remarkably affect CAT activity in the gills and muscle. The levels of lipid peroxidation (LPO) increased dose dependently, showing tissue specificity with the highest level in the liver, then the gills, followed by muscles. Overall, higher sensitivity to oxidative stress induced by MeHg was detected in the liver than the gills and muscle. These findings improve our understanding of the tissue-specific accumulation of heavy metals and their roles in antioxidant responses in marine fish subjected to MeHg exposure.

Summary Background Cabozantinib is a multikinase inhibitor of MET, VEGFR, AXL, and RET, which also has an effect on the tumour immune microenvironment by decreasing regulatory T cells and myeloid-derived suppressor cells. In this study, we examined the activity of cabozantinib in patients with metastatic platinum-refractory urothelial carcinoma. Methods This study was an open-label, single-arm, three-cohort phase 2 trial done at the National Cancer Institute (Bethesda, MD, USA). Eligible patients were 18 years or older, had histologically confirmed urothelial carcinoma or rare genitourinary tract histologies, Karnofsky performance scale index of 60% or higher, and documented disease progression after at least one previous line of platinum-based chemotherapy (platinum-refractory). Cohort one included patients with metastatic urothelial carcinoma with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Two additional cohorts that enrolled in parallel (patients with bone-only urothelial carcinoma metastases and patients with rare histologies of the genitourinary tract) were exploratory. Patients received cabozantinib 60 mg orally once daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate by RECIST in cohort one. Response was assessed in all patients who met the eligibility criteria and who received at least 8 weeks of therapy. All patients who received at least one dose of cabozantinib were included in the safety analysis. This completed study is registered with ClinicalTrials.gov , NCT01688999 . Findings Between Sept 28, 2012, and Oct, 20, 2015, 68 patients were enrolled on the study (49 in cohort one, six in cohort two, and 13 in cohort three). All patients received at least one dose of cabozantinib. The median follow-up was 61·2 months (IQR 53·8–70·0) for the 57 patients evaluable for response. In the 42 evaluable patients in cohort one, there was one complete response and seven partial responses (objective response rate 19%, 95% CI 9–34). The most common grade 3–4 adverse events were fatigue (six [9%] patients), hypertension (five [7%]), proteinuria (four [6%]), and hypophosphataemia (four [6%]). There were no treatment-related deaths. Interpretation Cabozantinib has single-agent clinical activity in patients with heavily pretreated, platinum-refractory metastatic urothelial carcinoma with measurable disease and bone metastases and is generally well tolerated. Cabozantinib has innate and adaptive immunomodulatory properties providing a rationale for combining cabozantinib with immunotherapeutic strategies. Funding National Cancer Institute Intramural Program and the Cancer Therapy Evaluation Program.

Metal selenides possess tremendous potentials due to their high specific capacity for potassium storage, however the sluggish K+ diffusion and polyselenide dissolution always result in inferior electrochemical performance. Herein, metal selenide (CoSe2) nanorods with engineered exposed plane incorporated in reduced graphene oxide nanosheet (sc-CoSe2@rGO) are fabricated. In the crystalline interior, such single-crystal structure can provide unhindered path for the fast K+ transfer. Besides, at the crystalline surface, the mainly exposed (011) facet with Co2+ rich state can induce the catalytic function with enormous reaction sites, which effectively transform the polyselenide to selenide with an enhanced selenium utilization. As expected, the as-prepared sc-CoSe2@rGO delivers satisfied specific capacity, prominent rate property, and superior cyclic stability (a reversible capacity of 157.7 mAh g−1 at high rate of 3.0 A g−1 after 600 cycles). This single-crystalline architecture design for intrinsic K-ion diffusion and surficial optimization is pioneeringly investigated, which provides a new insight into designing and fabricating metal-ion storage materials.

Due to the high toxicity in aquatic food chain, the toxic effects of methylmercury (MeHg) on organisms have caused widespread concerns, but little has been reported on its effects on marine fish. The acute and sub-lethal toxicities of MeHg chloride to an important aquaculture species in southeast coast of China - large yellow croaker (Pseudosciaena crocea) embryos and larvae were investigated in this study. Acute toxicity tests showed that the 48-h LC50 values of methylmercury to fish embryos and larvae were 28.39 (21.33–33.98) and 18.27 (11.33–29.29) μg L−1, respectively. The 96-h LC50 value for larvae was 9.28 (4.41–14.49) μg L−1, which indicated that fish larvae were more sensitive to MeHg than the embryos. On the other hand, MeHg exposure induced delayed hatching process, lower yolk absorption rate, higher morphological malformations at concentrations ≥ 1 μg L−1, and caused higher larvae heart rate, lower survival and hatching success at concentrations ≥ 5, 10, and 20 μg L−1, respectively. The results suggested that the hatching, survival and growth of the large yellow croaker during the early life stages may serve as sensitive biomarkers for marine MeHg pollution.

The BF3·OEt2-mediated disproportionate coupling reaction of sodium sulfinates was found for the first time. In this reaction, various S–S(O)2 bonds can be formed, efficiently giving thiosulfonates in moderate to excellent yields. As a convenient protocol for the synthesis of symmetrical and unsymmetrical thiosulfonates, its reaction mechanism involves the formation of a thiyl radical and sulfonyl radical via a sulfinyl radical disproportionation. What is more, this transformation can also be applied practically as a gram-scale reaction and to the two-step synthesis of sulfone and sulfonamide in one pot in situ using thiosulfonate as an intermediate.

Magnetic and transport properties of triangular-lattice Ni 1.8 Ge single crystal have been studied. The results reveal that Ni 1.8 Ge is a metal with an obvious magnetic anisotropy. The compound exhibits ferrimagnetic correlations along both directions. However, the long-range magnetic order was not observed due to the geometrical frustration arising from the triangular nickel lattice. At low temperature, the electron-magnon scattering and spin fluctuation have obvious contributions to the resistivity and magnetoresistance, indicating the existence of short-range dynamic magnetic ordering.

One of the most important factors governing the photovoltaic efficiency and environmental stability of Perovskite Solar Cells (PSCs) is the quality of their perovskite films. However, the present study demonstrates that CH3NH3PbI3 perovskite films after anti-solvent washing are far from perfect on the surface, where the crystallization degree is quite low with complex multi-phases associated with numerous defects and notable chemical inhomogeneity. Herein, we report a novel anti-solvent washing treatment simply using Hydrogen Iodide (HI) additive in chlorobenzene (CB) which can enormously improve CH3NH3PbI3 films surface with high crystallization phase purity and chemical homogeneity, leading to excellent structural stability under humidity, heat and even tensile force. Based on such high quality films with defect-less surface, fabricated planar PSCs with an architecture of ITO/TiO2/CH3NH3PbI3/Spiro-OMeTAD/MoOx/Au present a champion PCE of 19.94% and improved stability under humidity. Moreover, fabricated flexible planar PSCs on PET/ITO substrates with a champion PCE of 17.32% are shown to be more robust under tensile force than their control devices. The present study thus not only provides more insight into the facile defects passivation process on the surface achieved via balancing halide ions, but also provides a practical but efficient treatment which can be widely used to fabricate high quality CH3NH3PbI3 films for environmentally stable high performance device applications.

Betulin is an active natural pentacyclic triterpene ingredient with valuable anti-cancer and anti-HIV efficacies. In the present study, an efficient approach was developed to screening and identification of metabolites and to assess the metabolic profiles of betulin in vivo using UHPLC-Q-TOF-MS/MS system based on multiple mass defect filter data acquisition (MMDF) and multiple data processing techniques. Based on the proposed method, 56 phase I and 6 phase II metabolites were detected in rats after oral administration of betulin. The main biotransformation routes of betulin were identified as demethylation, dehydroxylation, deoxidization, dehydration. Conjugation with sulfate, taurine, cysteine and N-acetylcysteine groups produced 6 phase II metabolites. This study not only provided useful information for further study of the pharmacology and mechanism of betulin in vivo, but also provided essential data for further pharmaceutical studies of other pentacyclic triterpenes.

An actinomycete strain, designated KLBMP S0039T, was isolated from the rhizosphere soil of Lycium Linn., collected from the coastal region in Lianyungang, Jiangsu Province, eastern PR China, and was studied to determine its taxonomic position. The isolate showed a combination of morphological and chemotaxonomic properties typical of the members of the genus Nocardia . The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell sugars were galactose, arabinose, glucose and ribose. The predominant menaquinone was identified as MK-8(H4ω-cycl). The diagnostic phospholipids were found to be diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and unknown lipids. The predominant cellular fatty acids were identified as C16 : 0, C18 : 0, C18 : 1ω9c, and 10-methyl C18 : 0 [tuberculostearic acid (TBSA)]. The G+C content of the genomic DNA was determined to be 68.2 mol%. The 16S rRNA gene sequence similarity indicated that KLBMP S0039T was most closely related to Nocardia neocaledoniensis NBRC 108232T (99.4 % 16S rRNA gene sequence similarity) and Nocardia asteroides NBRC 15531T (99.2 %), similarities to other type strains of species of the genus Nocardia were found to be less than 98.6 %. However, DNA–DNA relatedness values and phenotypic data indicated that KLBMP S0039T could be clearly distinguished from the closely related species of the genus Nocardia . On the basis of polyphasic taxonomic data, it is concluded that KLBMP S0039T represents a novel species of the genus Nocardia , for which the name Nocardia rhizosphaerihabitans sp. nov. is proposed. The type strain is KLBMP S0039T (=KCTC 39693T=CGMCC 4.7329T).

The micro-stripe structure was prepared by laser interference induced forward transfer technique, composed of Ag nano-particles (NPs). The effects of the film thickness with the carbon nano-particles mixed polyimide (CNPs@PI), Ag film thickness, and laser fluence were studied on the transferred micro-stripe structure. The periodic Ag micro-stripe with good resolution was obtained in a wide range of CNPs@PI film thickness from ∼0.5 to ∼1.0 μm for the Ag thin film ∼20 nm. The distribution of the Ag NPs composing the micro-stripe was compact. Nevertheless, the average size of the transferred Ag NPs was increased from ∼41 to ∼197 nm with the change of the Ag donor film from ∼10 to ∼40 nm. With the increase of the laser fluence from 102 to 306 mJ·cm−2 per-beam, the transferred Ag NPs became aggregative, improving the resolution of the corresponding micro-stripe. Finally, the transferred Ag micro-stripe exhibited the significant surface enhanced Raman scattering (SERS) property for rhodamine B (RhB). While the concentration of the RhB reached 10–10 mol·L−1, the Raman characteristic peaks of the RhB were still observed clearly at 622, 1359 and 1649 cm−1. These results indicate that the transferred Ag micro-stripe has potential application as a SERS chip in drug and food detection.

A tissue-smashing based ultra-rapid extraction coupled with ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method was developed to determine 10 major triterpenoid saponins from Pulsatilla herbs. Compound 4 was characterized as betulinic acid glycoside 3-O-α-arabinopyranosyl-28-O-β-glucopyranosyl-23-hydroxy with HR-ESI-MS, 1H-NMR and 13C-NMR experiment. The MS spectra result showed that the ionization of compound 4 was more efficient in the positive mode. Meanwhile, the ions at m/z 789.6 and m/z 627.5 were selected as precursor and product ion for the determination, respectively. The chromatographic separation was carried out on a Phenomenex Kinetex C18 column using a gradient mobile phase system composed of 0.1% formic acid both in methanol and water at a flow rate of 0.4 mL/min. The detection was performed by multiple reaction monitoring mode, using electrospray ionization in the positive and negative mode. The total run time was 6 min. The calibration curves possessed good linearity with all coefficients higher than 0.9987. The intra- and interday precisions were no more than 4.9%, and the average recoveries were from 97.6% to 103.4% with RSD

Alpha-synuclein (α-syn) is associated to Parkinson's disease (PD). The aggregated form of α-syn has potential neurotoxicity. Thus, the clearance of α-syn aggregation is a plausible strategy to delay disease progression of PD. In our study, we found that the treatment of Ginkgolide B (GB) and Ginkgolide K (GK) reduced cell death, and enhanced cell proliferation in SH-SY5Y cells, which overexpressed A53T mutant α-syn. Surprisingly, GK, but not GB, promoted the clearance of A53T α-syn, which can be abolished by autophagy inhibitor 3-methyladenine, indicating that GK-induced autophagy intervened in the clearance of A53T α-syn. However, GK did not affect the NEDD4 that belongs to the ubiquitin ligase in the endosomal-lysosomal pathway. Furthermore, GK treatment inhibited the p-NF-kB/p65 and induced the PI3K, BDNF, and PSD-95. Taken together, GK increased the clearance of α-syn, reduced cell death, and triggered complex crosstalk between different signaling pathways. Although our results show a potentially new therapeutic candidate for PD, the details of this mechanism need to be further identified.

A novel Gram-stain-positive, aerobic bacterium, designated strain DHS C021T, was isolated from a limestone sample collected from the Puding Karst Ecosystem Research Station of Guizhou Province, southwest China. This strain developed branched vegetative mycelia, and its aerial mycelia fragmented into rod-shaped spores. The cell-wall peptidoglycan contained meso-diaminopimelic acid and the whole-cell sugars comprised galactose, ribose and mannose. The respiratory quinone was identified as menaquinone MK-9(H4). The major cellular fatty acids were iso-C14 : 0 and iso-C16 : 0. The phospholipids detected were diphosphatidylglycerol, phosphatidylethanolamine, hydroxyl-phosphatidyethanolamine, phosphatidylinositol, phosphotidylinositolmannosides and one unidentified phospholipid. The genomic DNA G+C content was 69.8 mol% and 16S rRNA gene sequence analysis showed that the strain belonged to the genus Lentzea and shared highest sequence similarity with Lentzea albida CGMCC 4.1727T (98.8 %) and Lentzea waywayandensis CGMCC 4.1646T (98.5 %). However, it could be distinguished from these reference strains based on the low levels of DNA–DNA relatedness (54.5±2.7 and 41.7±3.2 %, respectively). On the basis of morphological, chemotaxonomic and phylogenetic characteristics, and DNA–DNA hybridization data, strain DHS C021T represents a novel species of the genus Lentzea , for which the name Lentzea pudingi sp. nov. is proposed. The type strain is DHS C021T (=CGMCC 4.7319T=KCTC 39694T).

Levels of most VOCs in foods are usually low because of their volatility, and human exposure to VOCs is expected to be mainly via inhalation of ambient and indoor air. However, dietary exposures to VOCs can be significant to overall exposures if elevated concentrations of VOCs are present in foods consumed in high amounts and/or on a regular basis, and this was demonstrated in this study with the occurrence data of toluene from the recent 2014 Canadian Total Diet Study (TDS). Concentrations of toluene in the composite samples of most food types from the 2014 TDS are low and similar to the results from the previous 2007 TDS with some exceptions, such as beef steak (670 ng/g (2014 TDS) vs. 14 ng/g (2007 TDS)), poultry, chicken and turkey (307 ng/g (2014 TDS) vs. 8.8 ng/g (2007 TDS)). Toluene concentrations in most of the grain-based and fast food composite samples from the 2014 TDS are considerably higher than those from the 2007 TDS, with the highest level of 4655 ng/g found in the composite sample of crackers from the 2014 TDS (compared to 18 ng/g from 2007 TDS). Dietary exposure estimates for toluene based on the occurrence results from the 2014 TDS show that for most of the age groups, grain-based foods are the primary source, accounting for an average of 77.5% of the overall toluene intake from the diet. The highest dietary exposures to toluene were observed for the adult age groups, with estimated average exposures ranging from 177.4 to 184.5 µg/d. Dietary exposure estimates to toluene are well below oral doses associated with toxicological effects and also below the maximum estimated intake (819 µg/d) from air inhalation for adult group (20 - 70 years) based on the results from CEPA (Canadian Environmental Protection Act) assessment in 1992.

An efficient route without metal catalyst has been developed for synthesis of 4-biphenylamino-5-halo-2(5H)-furanones. The antitumor activities against various tumor cells of all the compounds have been evaluated by MTT assay. Among them, the compound 3j exhibits significant inhibitory activity against MCF-7 human breast cancer cells with an IC50 value of 11.8 μM and low toxicity toward HaCaT human normal cells. The mechanism studies confirm that 3j can induce cell cycle arrest at G2/M phase in MCF-7 cells. Compared with compound 3e, 3j has stronger binding affinity to c-myc G-quadruplex (G4) DNA via π-π stacking and H-bonding interactions. Western blot analysis also further confirms that compound 3j can down-regulate the expression of c-myc in MCF-7 cells.