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Aurantinins (ARTs) are antibacterial polyketides featuring a unique 6/7/8/5-fused tetracyclic ring system and a triene side chain with a carboxyl terminus. Here we identify the art gene cluster and dissect ART’s C-methyl incorporation patterns to study its biosynthesis. During this process, an apparently redundant methyltransferase Art28 was characterized as a malonyl-acyl carrier protein O-methyltransferase, which represents an unusual on-line methyl esterification initiation strategy for polyketide biosynthesis. The methyl ester bond introduced by Art28 is kept until the last step of ART biosynthesis, in which it is hydrolyzed by Art9 to convert inactive ART 9B to active ART B. The cryptic reactions catalyzed by Art28 and Art9 represent a protecting group biosynthetic logic to render the ART carboxyl terminus inert to unwanted side reactions and to protect producing organisms from toxic ART intermediates. Further analyses revealed a wide distribution of this initiation strategy for polyketide biosynthesis in various bacteria., Aurantinins are polyketides with unusual connectivities and broad antibacterial activity. Here the authors show the biosynthesis of aurantinins, which proceeds via an on-line methyl esterification at the terminus that enables the iterative chain elongations prior to condensation and cyclization.

The synthesis of dibenzofurans and bicycloalkanes from biomass is important for sustainable high-value chemicals and high-density fuels. Currently, their biomass-based precursor is mainly derived from lignin with limited yields. Herein, we propose a cellulose-based synthesis route for dibenzofurans with a yield of 72.3% via the integration of oxidative coupling of 1,2,4-benzenetriol to diphenol combined with subsequent dehydration under environmentally friendly reaction conditions. After hydrodeoxygenation, bicycloalkanes are obtained with a yield of 70.5% by catalysis performed over Pd/C and various zeolites. This work provides a powerful cellulose-based strategy for the synthesis of dibenzofurans and bicycloalkanes, which was previously unattainable in the conventional lignin-based route.

In contrast to the broad use of terephthalic acid as a building block for generating metal-organic architectures, functionalized terephthalate ligands remain significantly less investigated. In the present study, 2-chloroterephthalic acid (CltaH2) was used as an unexplored linker for assembling a new series of metal(II) coordination polymers (CPs) formulated as {[Cu2(μ-Clta)(μ4-Clta)(bipy)2]·2H2O}n (1), {[Cu2(μ-Clta)(μ4-Clta)(phen)2]·2H2O}n (2), [Co3(μ4-Clta)3(phen)2]n (3), {[Zn4(μ3-Clta)2(μ4-Clta)(μ3-OH)2(phen)2]·2H2O}n (4), {[Cd(μ3-Clta)(phen)]·H2O}n (5), [Co2(μ-Clta)(μ4-Clta)(μ-bpa)2]n (6), [Zn2(μ4-Clta)(μ4-biim)]n (7), and [Cd(μ-Clta)(H2biim)2]n (8). These compounds were prepared hydrothermally from the respective metal(II) chlorides, CltaH2, and different N-donor supporting ligands acting as mediators of crystallization (i.e., bipy, 2,2′-bipyridine; phen, 1,10-phenanthroline; bpa, bis(4-pyridyl)amine; H2biim, 2,2′-biimidazole). The structures of the coordination polymers 1-8 range from one-dimensional chains (5 and 8) and two-dimensional layers (1-3) to three-dimensional (3D) frameworks (4, 6, and 7); the latter also include 3D + 3D interpenetrated examples (4, 6). Apart from different dimensionalities, the compounds also feature distinct topologies, namely, 3,4L13 in 1 and 2, 3,4,6L12 in 3, pcu in 4, SP 1-periodic net (4,4)(0,2) in 5, sqc65 in 6, 2C1 in 8, and a new kir1 topology in 7. Given the similarity of the reaction conditions, the obtained wide diversity of structures is primarily determined by the type of metal(II) node and/or crystallization mediator. All the CPs were also screened as heterogeneous catalysts in a model CO2 fixation reaction, namely, in the coupling of epoxide (epichlorohydrin) with carbon dioxide, under atmospheric pressure, and in the absence of added solvent, to produce the corresponding cyclic carbonate. The catalytic reactions were optimized for CP 4, which revealed the best activity (up to 71% product yields), good stability, and recyclability for up to four reaction steps. Finally, CPs 3-8 are the first examples of cobalt, zinc, and cadmium coordination compounds assembled from 2-chloroterephthalic acid, thus widening its very limited application in the design of functional metal-organic architectures. ©

A general and efficient method is reported for the direct mono-1-alkenylation of 9H-carbazole molecules with divalent palladium as a catalyst and an N-(2-pyridyl)sulfanyl directing group. This method also provides an efficient synthetic route for the synthesis of cross-dialkenylated carbazoles.

A novel biphenyl-tricarboxylic acid, 3,2′,4′-biphenyl-tricarboxylic acid (H3bta), was used as a versatile linker for preparing a new series of nickel(II), zinc(II), and cadmium(II) coordination polymers (CPs) and complexes, formulated as {[Cd(μ-Hbta)(2,2′-bipy)(H2O)]·3H2O}n (1), {[Ni(μ-Hbta)(4,4′-bipy)(H2O)3]·H2O}n (2), [M2(μ-Hbta)2(4,4′-bipy)2(H2O)2]·2H2O (M = Zn (3) and Cd (4)), {[Cd2(μ4-bta)(μ-Cl)(phen)2]·2H2O}n (5), {[Zn2(μ3-bta)(2,2′-bipy)2(H2O)3][Zn(μ-bta)(2,2′-bipy)(H2O)]·3H2O} (6), {[Cd3(μ4-bta)2(2,2′-bipy)3]·4H2O}n (7), {[Zn3(μ3-bta)2(H2biim)2(μ-H2biim)(H2O)2]·2H2O}n (8), and [Zn3(μ6-bta)2(py)2]n (9). These coordination compounds were hydrothermally assembled from the metal(II) chlorides, H3bta as a principal building block and N-donor ancillary ligands as crystallization mediators (i.e., 2,2′-bipyridine, 2,2′-bipy; 4,4′-bipyridine, 4,4′-bipy; 1,10-phenanthroline, phen; 2,2′-biimidazole, H2biim; or pyridine, py). All the synthesized products 1–9 were characterized by standard solid-state methods including elemental analysis, IR spectroscopy, thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction. The structures of 1–9 range from 0D dimers (3 and 4) to 1D coordination polymers (1, 2, 5, and 6) and 2D metal–organic layers (7–9). Such a diversity of structures is explained by the differences in metal(II) centers, deprotonation levels of H3bta, and crystallization mediators. From a topological perspective, the obtained structures include 2C1 chains (in 1, 2, and 6), pcu H-bonded nets (in 3 and 4), SP 1-periodic nets (in 5), and 4,5L51 (in 7) and hcb (in 8) layers. For compounds 1–9, luminescence properties were also evaluated. Besides, the catalytic behavior of the obtained products was screened in the cyanosilylation of benzaldehydes with trimethylsilyl cyanide to give cyanohydrin products under mild conditions, including an optimization of various reaction parameters and an investigation of the substrate scope. Among the tested compounds, 3 acts as the most efficient and recyclable heterogeneous catalyst with up to 96% product yields. By presenting the unique examples of coordination compounds derived from H3bta, this study introduces its use as a new tricarboxylate linker for assembling functional coordination polymers and metal complexes.

A triphenyl-pentacarboxylic acid, 3,5-di(2′,4′-dicarboxylphenyl)benzoic acid (H5ddba), was applied as an adaptable linker for the hydrothermal assembly of eight new metal(II) coordination polymers (CPs) and complexes, formulated as [Cu2(μ-H3ddba)2(phen)2] (1), {[Cd2(μ4-Hddba)(phen)2(H2O)2]·2H2O}n (2), [M4(μ3-Hddba)2(2,2′-bipy)6(μ-H2O)]·6H2O (M = Ni (3), Mn (4)), {[Co2(μ5-Hddba)(μ-4,4′-bipy)1.5(H2O)]·H2O}n (5), {[Zn2(μ5-Hddba)(4,4′-bipy)1.5]·4,4′-bipy·2H2O}n (6), [Mn2(μ6-Hddba)(H2biim)(H2O)]n (7), and {[Cd2(μ7-ddba)(Hbpa)]·5H2O}n (8). The products 1–8 were generated from metal(II) chlorides, H5ddba, and various N-donor supporting ligands acting as mediators of crystallization (i.e., phen: 1,10-phenanthroline; 2,2′-bipy: 2,2′-bipyridine; 4,4′-bipy: 4,4′-bipyridine; H2biim: 2,2′-biimidazole; or bpa: bis(4-pyridyl)amine). All compounds were analyzed by standard methods (C/H/N analysis, FTIR, TGA and PXRD) including single-crystal X-ray diffraction. The structural multiplicity of 1–8 ranges from discrete dimers (1) or tetramers (3 and 4) to a 1D coordination polymer (2) and 3D metal–organic frameworks (5–8). Topological analysis of simplified H-bonded or metal–organic networks disclosed fcu (1), 2C1 (2), dia (3 and 4), sra (6), 3,4,7T3 (8), and unprecedented (5 and 7) topologies. The catalytic activity of 1–8 was investigated in a model Knoevenagel condensation between benzaldehydes and malononitrile, resulting in up to 99% yields of condensation products. The substrate scope, catalyst recycling, and effects of different reaction parameters were investigated. Finally, this work extends the use of H5ddba as an aromatic pentacarboxylate building block for the design of new metal–organic architectures with captivating structures and functional properties.

Zinc oxide nanoparticles (ZnO NPs) are known for their antibacterial, antioxidant, and anti-inflammatory activities. Moreover, ZnO NPs can stimulate cell migration, re-epithelialization, and angiogenesis. All these attributes are highly relevant to wound healing. Local administration of ZnO NPs to the wound can be achieved through electrospun nanofibers. We hypothesized that the use of poly(lactide-co-glycolic acid) (PLGA)/silk fibroin (SF) nanofiber-based delivery of ZnO would maintain the bioavailability of NPs on the wound area and synchronization with the unique structural features of electrospun nanofibers, could stimulate wound closure, re-epithelialization, collagen deposition, cellular migration, and angiogenesis. In this study, we fabricated PLGA/SF (PS) nanofibrous (NF) membranes with and without ZnO NPs and extensively characterized them for various physicochemical and biological attributes. Scanning electron microscopy (SEM) revealed smooth fibers and ZnO concentration-dependent increase in the fiber diameter. Transmission electron microscopy (TEM) also confirmed the encapsulation of ZnO NPs in the polymer matrix. The successful loading of ZnO was further confirmed by X-ray diffraction. Furthermore, mechanical testing revealed a ZnO concentration-dependent increase in the tensile strength. Moreover, biocompatibility was evaluated through in vitro cell culture. A mild anti-oxidant activity was also noted mainly due to the presence of silk fibroin. In vitro antibacterial tests revealed a ZnO concentration-dependent increase in antibacterial activity and PLGA/SF/3% ZnO (PSZ3) remained completely active against E. coli and S. aureus. More importantly, NF membranes were evaluated for their in vivo wound healing potential. The PSZ3 NF membrane not only facilitated the early wound closure but also remarkably enhanced the quality of wound healing confirmed through histopathological analysis. Re-epithelialization, granulation tissue formation, collagen deposition, and angiogenesis are some of the key parameters significantly boosted by ZnO loaded composite NF membranes. Based on extensive characterization and biological evaluation, the PSZ3 NF membrane has turned out to be a potential candidate for wound healing applications.

Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew (Tupaia belangeri chinensis) is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu506 of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-β but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.

Introduction Hepatitis B virus (HBV) is a global health concern that can cause acute and chronic liver diseases. Thus, there is an urgent need to research novel anti-HBV agents. Our previous reports show that N-phenylbenzamide derivatives exert broad-spectrum antiviral effects against HIV-1, HCV, and EV71 by increasing intracellular levels of APOBEC3G (A3G). As A3G is capable of inhibiting the replication of HBV, we screened the N-phenylbenzamide derivatives against HBV. Methods In this study, a new derivative, N-(4-chlorophenyl)-4-methoxy-3-(methylamino) benzamide (IMB-0523), was synthesized and its anti-HBV activity was evaluated in vitro and in vivo. The acute toxicity and pharmacokinetic profiles of IMB-0523 were also investigated. Results Our results show that IMB-0523 has higher anti-HBV activity in both wild-type HBV (IC50: 1.99 µM) and drug-resistant HBV (IC50: 3.30 µM) than lamivudine (3TC, IC50: 7.37 µM in wild-type HBV, IC50: >440 µM in drug-resistant HBV). The antiviral effect of IMB-0523 against HBV may be due to an increased level of intracellular A3G. IMB-0523 also showed low acute toxicity (LD50: 448 mg/kg) in mice and promising PK properties (AUC0-t: 7535.10±2226.73 µg·h/L) in rats. Further, IMB-0523 showed potent anti-HBV activity in DHBV-infected ducks. Conclusion Thus, IMB-0523 may be a potential anti-HBV agent with different mechanisms than current anti-HBV treatment options.

In this study, we, for the first time, demonstrate a general solid-phase pyrolysis method to synthesize hybrid transition metal nanocrystal-embedded graphitic carbon nitride nanosheets, namely M-CNNs, as a highly efficient oxygen electrocatalyst for rechargeable Zn–air batteries (ZABs). The ratios between metallic acetylacetonates and the g-C3N4 precursor can be controlled where Fe-CNNs−0.7, Ni-CNNs−0.7 and Co-NNs−0.7 composites have been optimized to exhibit superior ORR/OER bifunctional electrocatalytic activities. Specifically, Co-CNNs−0.7 exhibited not only a comparable half-wave potential (0.803 V vs. RHE) to that of the commercial Pt/C catalyst (0.832 V) with a larger current density for the ORR but also a lower overpotential (440 mV) toward the OER compared with the commercial IrO2 catalyst (460 mV), revealing impressive application in rechargeable ZABs. As a result, ZABs using Co-CNNs−0.7 as the cathode exhibited an excellent peak power density of 85.3 mW cm−2 with a specific capacity of 675.7 mA h g−1 and remarkable cycling stability of 1000 cycles, outperforming the commercially available Pt/C + IrO2 catalysts. This study highlights the synergy from heterointerfaces in oxygen electrocatalysis, thus providing a promising approach for advanced metal–air cathode materials.

Total polysaccharide (i.e., GLP-UCE) was effectively isolated from the crude polysaccharide extract powder of Ganoderma lucidum by ultrasonic-circulating extraction, which was separated into three fractions (i.e., GLP-U40, GLP-U60, and GLP-U80) by ethanol fractional precipitation. The detection of antioxidant enzymes (GSH-Px, SOD) and oxidation metabolites (MDA, LF); liver function test of ALT, AST, and LDH; and western blot for antioxidant proteins of GSH-Px and MMP-2 showed that the GLP-UCE displayed a favorable in vivo antioxidant and hepatoprotective activities for reducing the oxidative damage in CCl4-hepatopathy SD rats. The GLP-UCE and its fractions were analyzed and compared by Fourier transform infrared (FT-IR), high-performance liquid chromatography, high-performance gel permeation chromatography, and antioxidant activity in vitro assay. These studies revealed that the fraction GLP-U80 exhibited stronger antioxidant activities in vitro than that of GLP-UCE and other fractions (p

An efficient photocatalytic dual decarboxylative alkenylation of α,β-unsaturated carboxylic acids and alkyl N-hydroxyphthalimide (NHP) esters mediated by triphenylphosphine and sodium iodide has been developed. This protocol proceeds under 456-nanometer irradiation by visible blue light in the absence of transition metals or organic dye based photoredox catalysts. The reaction is successfully applied to a wide range of redox-active esters derived from aliphatic carboxylic acids (1°, 2° and 3°) and α-amino acids, enabling transformations of diverse α,β-unsaturated carboxylic acids to α,β-alkylated styrenes with high efficiency and excellent selectivity under mild conditions.

The major challenge in the synthesis of high-density biofuels is to identify the bio-based source for C–C cyclic compounds and C–C coupling reactions with a suitable selectivity. Herein, we selectively synthesize 1,2,4-benzenetriol (BTO) with a yield of 51.4% from cellulose-derived 5-hydromethylfurfural via a ring-rearrangement reaction. The cellulose-derived route is a more meaningful route for the C–C cyclic compounds compared to the traditional hemicellulose- and lignin-derived routes. Furthermore, BTO is very easily dimerized via a C–C oxidative coupling reaction, showing a yield of 94.4% and selectivity of nearly 100% under environmentally friendly reaction conditions. After hydrodeoxygenation, bicyclohexane is obtained with a yield of 87.4%. This work not only provides a promising route to produce C–C cyclic fine compounds based on a cellulose-derived route, but also shows a highly efficient synthesis route for high-density biofuels via the C–C oxidative coupling reaction.

This work describes the application of an unexplored aromatic tetracarboxylate building block, 2,3′,4,4′-diphenyl ether tetracarboxylic acid (H4deta), for the synthesis of manganese(II) and cadmium(II) coordination polymers (CPs). Five new products, formulated as [Mn2(μ6-deta)(phen)2]n (1), [Cd2(μ6-deta)(phen)2]n (2), [Mn2(μ6-deta)(2,2′-bipy)2]n (3), [Cd2(μ5-deta)(4,4′-bipy)2(H2O)2]n·2nH2O (4), and [Cd2(μ6-deta)(py)(H2O)2]n (5), were assembled using a hydrothermal protocol from the respective metal(II) chlorides, H4deta, and different mediators of crystallization, namely 1,10-phenanthroline (phen), 2,2′-bipyridine (2,2′-bipy), 4,4′-bipyridine (4,4′-bipy), or pyridine (py). All the CPs 1–5 were obtained as stable crystalline products and characterized by conventional solid-state methods (elemental analysis, FTIR, UV-vis, TGA, and PXRD) and single-crystal X-ray diffraction. The structures of 1–3 feature decorated honeycomb-like 2D double layers of a 3,6L66 topological type. Compound 4 reveals a trinodal 4,4,5-connected 3D metal–organic framework (MOF) with a unique topology, while the 2D coordination polymer 5 discloses a binodal 4,6-connected layer with a 4,6L45 topology. The structural and topological traits, thermal stability, luminescence properties and photocatalytic activity toward methylene blue degradation were studied for the obtained compounds. In particular, MOF 4 acts as an active, stable, and recyclable photocatalyst for the UV-light-assisted discoloration of methylene blue in water under ambient conditions. By introducing a novel type of flexible tetracarboxylic acid linker, the present study discloses the first manganese and cadmium compounds derived from H4deta as an unexplored polycarboxylate building block, thus contributing to intensive research on functional metal–organic architectures.

Although various geochemical and geophysical investigations have already indicated a great resource potential in the Xisha area of the South China Sea, the origin of organic matter and molecular evidence for tracing the migration of hydrocarbons from deep petroleum reservoirs are still lacking. In this study, systematic organic geochemical analyses, including bulk organic matter parameters and lipid biomarkers were performed for deep sediments from two cores. The C/N ratios and δ13C and δ15N values of organic matter in most of the samples, together with the maxima of short-chain n-alkanoic acids and mid-chain n-alkanols, high abundances of monounsaturated fatty acids C18:1ω9 and C22:1ω13, jointly indicate the dominance of marine organic matter. n-Alkanes in sediments from core GMGS4-XH-W06B are characterized by small unresolved complex mixture (UCMs) humps, high odd/even predominance (OEP) and carbon preference index (CPI) values, clearly exhibiting characteristics of modern sediments. However, the sediments for core GMGS4-XH-W03B are featured with big UCMs, associated with OEP and CPI values around 1.0, showing signatures of petroleum hydrocarbons from high maturity sources. Considering the geologic background, the biomarker signatures are solid evidence for indicating the existence of underlying petroleum reservoirs, and may provide the valuable information for assessing the hydrocarbon resources in the Xisha area.

Cyperus esculentus L. leaves (CLL) are agricultural by-products produced from Cyperus esculentus L. harvesting, and can be used as livestock feed despite their low economic value for human consumption. This study aims to develop a favorable approach to processing Cyperus esculentus L. by-product as coarse fodder. The chopped CLL was pretreated by (1) mixing with canola straw at a 4:1 ratio, or (2) wilting it for 8 h, then it ensiling with or without compounded lactic acid bacteria (LAB) additives for 60 days. Our results demonstrated that compounded LAB additives: improved CLL silage fermentation quality by increasing acetic acid and lactic acid contents and decreasing ethanol and ammonia-N contents; preserved nutrients by raising the level of crude protein and water soluble carbohydrates; modified the bacterial community by increasing the relative abundance of Lactobacillus while decreasing the relative abundance of undesirable Enterococcus; and also might improve animal health by increasing the relative concentrations of antioxidant substances (such as 7-galloylcatechin) and antibacterial compounds (such as ferulic acid). This study provides strong evidence that Cyperus esculentus L. by-product can be a potential livestock feed after being ensiled with compounded LAB additives.

Methane hydrate in the South China Sea (SCS) has extensively been considered to be biogenic on the basis of its δ13C and δD values. Although previous efforts have greatly been made, the contribution of thermogenic oil/gas has still been underestimated. In this study, biomarkers and porewater geochemical parameters in hydrate-free and hydrate-bearing sediments in the Taixinan Basin, the SCS have been measured for evaluating the contribution of petroleum hydrocarbons to the formation of hydrate deposits via a comparative study of their source inputs of organic matters, environmental conditions, and microbial activities. The results reveal the occurrence of C14–C16 branched saturated fatty acids (bSFAs) with relatively high concentrations from sulfate-reducing bacteria (SRBs) in hydrate-bearing sediments in comparison with hydrate-free sediments, which is in accord with the positive δ13C values of dissolved inorganic carbon (DIC), increasing methane concentrations, decreasing alkalinity, and concentration fluctuation of ions (Cl−, Br−, SO42−, Ca2+, and Mg2+). These data indicate the relatively active microbial activities in hydrate-bearing sediments and coincident variations of environmental conditions. Carbon isotope compositions of bSFAs (−34.0‰ to −21.2‰), n-alkanes (−34.5‰ to −29.3‰), and methane (−70.7‰ to −69.9‰) jointly demonstrate that SRBs might thrive on a different type of organic carbon rather than methane. Combining with numerous gas/oil reservoirs and hydrocarbon migration channels in the SCS, the occurrence of unresolved complex mixtures (UCMs), odd-even predominance (OEP) values (about 1.0), and biomarker patterns suggest that petroleum hydrocarbons from deep oil/gas reservoirs are the most probable carbon source. Our new results provide significant evidence that the deep oil/gas reservoirs may make a contribution to the formation of methane hydrate deposits in the SCS.

Background: Our previous study successfully identified that 3,3-Dimethylquercetin (DMQ) acted as a potent anticancer agent against human colon cancer cell lines RKO. Thus, this study was conducted to investigate the underlying mechanism by which DMQ displayed inhibitory activity in RKO cells. Methods: Flow cytometry was used to evaluate the effect of DMQ on the cell cycle arrest, as well as the mitochondrial membrane potential in RKO cells. DAPI staining and DNA fragmentation ladder assays were performed to assess the apoptosis inducing activity of DMQ. Furthermore, western blot analysis was conducted to examine the expression of related proteins responsible for the cell cycle arrest and apoptosis. Results: Treatment with DMQ caused a significant increase in the fraction of G2/M cells, and induced remarkable apoptosis. Furthermore, western blot analysis showed that DMQ arrested cells at G2/M checkpoint by down-regulation of cyclin B1, cdc2 and cdc25c and up-regulation of p21, and induced cell apoptosis via affecting the ratio of Bax/Bcl-2, causing loss of the mitochondrial membrane potential and enhancing the expression of cleaved caspase-9 (C-caspase-9) and cleaved caspase-3 (C-caspase-3). Conclusion: These data showed that DMQ could suppress RKO cell growth by arresting RKO cells at G2/M checkpoint and inducing mitochondria-dependent cell apoptosis. Our findings shed light on the potential use of DMQ as a chemotherapeutic agent for CRC.

Polyphenols are plant derived compounds that exert many beneficial health effects to the human host. However, associated health benefits of dietary polyphenol are highly dependent on their intestinal metabolism, bioavailability, and absorption. Bifidobacteria, which represent the key members of gut microbiota, have been suggested to promote gut microbial homeostasis and may be involved in the metabolism of polyphenols. In this study, the capabilities of thirteen Bifidobacterium strains in hydrolysing polyphenol glycosides were evaluated. Among the tested strains, Bifidobacterium breve MCC1274 was found to possess the highest β-glucosidase activity and strong capability to convert daidzin and trans-polydatin to their aglycones; while kinetic analysis revealed that B. breve MCC1274 hydrolysed more than 50% of daidzin and trans-polydatin at less than 3 h of incubation. Further investigation using rats with an antibiotics-disturbed microbiome revealed that following the ingestion of daidzin glycoside, oral administration of B. breve MCC1274 significantly enhanced the plasma concentration of daidzein in rats pre-treated with antibiotics as compared to antibiotics-pre-treated control and non-treated control groups. The relative abundance of Actinobacteria and the total numbers of B. breve were also significantly higher in antibiotics-pre-treated rats administered with B. breve MCC1274 than that of the control groups. These findings suggest that B. breve MCC1274 is effective in enhancing the bioavailability of daidzein in the gut under dysbiosis conditions and may potentially improve intestinal absorption of isoflavones and promote human health.

New coordination polymers of cobalt(II), namely, [Co(μ4-cpna)(H2O)2]n (1), [Co(μ3-cpna)(phen)(H2O)]n·nH2O (2), [Co3(μ4-dppa)2(H2O)6]n·2nH2O (3), and [Co3(μ5-dppa)2(μ-4,4′-bipy)(H2O)2]n·4nH2O (4), h...

An aromatic tricarboxylic acid, 4-(6-carboxy-pyridin-3-yl)-isophthalic acid (H3cpia), was applied as a building block for the hydrothermal syntheses of a new series of twelve metal(II) (M = Mn, Co, Ni, Zn, Cd, Pb) coordination compounds, namely [Mn(H2cpia)2(H2O)2] (1), [M(Hcpia)(phen)(H2O)2] (M = Co, 2; Ni, 3; Zn, 4), [Zn(Hcpia)(2,2′-bipy)(H2O)2]5·4H2O (5), [Zn2(μ-Hcpia)2(2,2′-bipy)2] (6), [M(μ-Hcpia)(phen)(H2O)]n (M = Co, 7; Cd, 8), {[Pb(μ4-Hcpia)]·2H2O}n (9), [Cd4(μ3-cpia)2Cl2(phen)6(H2O)2]·10H2O (10), {[Zn3(μ3-cpia)2(phen)3]·10H2O}n (11), and {[Zn4(μ4-cpia)2(μ-OH)2(μ-4,4′-bipy)2]·4,4′-bipy·2H2O}n (12). These products were assembled from aqueous mixtures containing metal(II) chlorides, H3cpia as a main tricarboxylic acid block, sodium hydroxide and an optional N-donor crystallization mediator (i.e., 1,10-phenanthroline, phen; 2,2′-bipyridine, 2,2′-bipy; or 4,4′-bipyridine, 4,4′-bipy). Compounds 1–12 were fully characterized by standard solid-state methods (IR spectroscopy, elemental analysis, TGA, PXRD, and single-crystal X-ray diffraction). Their structures range from discrete 0D monomers (1–5), dimer (6) or tetramer (10) to 1D coordination polymers (7, 8, and 11) and 2D metal–organic layers (9 and 12). Structural and topological features of H-bonded and metal–organic architectures were highlighted, showing that the structural diversity of 1–12 is influenced by the type of metal(II) node, the level of deprotonation of H3cpia, reaction temperature, and presence of crystallization mediator. Thermal behavior, magnetic, luminescent and photocatalytic properties of selected compounds were investigated and discussed. In fact, cobalt(II) coordination polymer 7 acts as a stable and recycable photocatalyst for the oxidative UV-light-assisted degradation of an organic dye in aqueous medium; methylene blue was used as a model dye pollutant in waste water. Finally, the obtained products 2 and 4–12 represent the first examples of Co, Zn, Cd, and Pb coordination compounds derived from H3cpia, thus introducing its application as a multifunctional picolinate-isophthalate building block for the generation of metal–organic architectures.

Summary Lipotoxicity plays an important role in the development of diabetic heart failure (HF). Canagliflozin (CAN), a marketed sodium-glucose co-transporter 2 inhibitor, has significantly beneficial effects on HF. In this study, we evaluated the protective effects and mechanism of CAN in the hearts of C57BL/6J mice induced by high-fat diet/streptozotocin (HFD/STZ) for 12 weeks in vivo and in HL-1 cells (a type of mouse cardiomyocyte line) induced by palmitic acid (PA) in vitro. The results showed that CAN significantly ameliorated heart functions and inflammatory responses in the hearts of the HFD/STZ-induced diabetic mice. CAN significantly attenuated the inflammatory injury induced by PA in the HL-1 cells. Furthermore, CAN seemed to bind to the mammalian target of rapamycin (mTOR) and then inhibit mTOR phosphorylation and hypoxia-inducible factor-1α (HIF-1α) expression. These results indicated that CAN might attenuate lipotoxicity in cardiomyocytes by inhibiting the mTOR/HIF-1α pathway and then show protective effects on diabetic hearts., Graphical abstract, Highlights • Canagliflozin ameliorated heart dysfunctions in HFD/STZ-induced diabetic mice • Canagliflozin inhibited lipotoxicity in palmitic acid-induced HL-1 cardiomyocytes • mTOR-HIF-1α pathway mediated lipotoxicity in cardiomyocytes • Canagliflozin bound to mTOR and inhibited mTOR-HIF-1α pathway, Human metabolism; Molecular biology

A genome-wide screening revealed that TRIM26 is a host factor for HCV replication and a new determinant for host tropism., Hepatitis C virus (HCV) remains a major human pathogen that requires better understanding of virus-host interactions. In this study, we performed a genome-wide CRISPR-Cas9 screening and identified TRIM26, an E3 ligase, as a critical HCV host factor. Deficiency of TRIM26 specifically impairs HCV genome replication. Mechanistic studies showed that TRIM26 interacts with HCV-encoded NS5B protein and mediates its K27-linked ubiquitination at residue K51, and thus promotes the NS5B-NS5A interaction. Moreover, mouse TRIM26 does not support HCV replication because of its unique six–amino acid insert that prevents its interaction with NS5B. Ectopic expression of human TRIM26 in a mouse hepatoma cell line that has been reconstituted with other essential HCV host factors promotes HCV infection. In conclusion, we identified TRIM26 as a host factor for HCV replication and a new determinant of host tropism. These results shed light on HCV-host interactions and may facilitate the development of an HCV animal model.

Doxorubicin (DOX), the first-line chemotherapy for bladder cancer, usually induces side effects. We previously demonstrated that green tea polyphenol EGCG had potent anti-tumor effect in bladder cancer via down regulation of NF-κB. This study aimed to investigate the additive/synergistic effect EGCG and DOX against bladder cancer. Our results demonstrated that the combined use of DOX and EGCG inhibited T24 and SW780 cell proliferation. EGCG enhanced the apoptosis induction effect of DOX in both SW780 and T24 cells and resulted in significant differences. Besides, EGCG promoted the inhibitory effect of DOX against bladder cancer cell migration. In addition, the in vivo results demonstrated that DOX in combination with EGCG showed the most potent anti-tumor effects among DOX, EGCG and DOX+EGCG treatment groups. Further mechanistic studies determined that the combination of DOX and EGCG inhibited phosphorylated NF-κB and MDM2 expression, and up-regulated p53 expression in tumor, as assessed by western blot and immunohistochemistry. Western blot in SW780 cells also confirmed that the combined use of EGCG and DOX caused significant increase in p53, p21, and cleaved-PARP expression, and induced significant inhibition in phosphorylated NF-κB and MDM2. When NF-κB was inhibited, the expression of p53 and p-MDM2 were changed, and the combination of DOX and EGCG showed no obvious effect in transwell migration and cell viability. In conclusion, the novel application of chemotherapy DOX and EGCG demonstrated potent anti-tumor, anti-migration and anti-proliferation effects against bladder cancer. EGCG enhanced the anti-tumor effect of DOX in bladder cancer via NF-κB/MDM2/p53 pathway, suggesting the potential clinical application against bladder cancer patients.

Diabetic wound (DW) healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation. Electrospun nanofibrous (NF) membranes, due to special structural features, are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner. Herein, we report a multifunctional composite NF membrane loaded with ZnO nanoparticles (NP) and oregano essential oil (OEO), employing a new loading strategy, capable to sustainedly co-deliver bioactive agents. Physicochemical characterization revealed the successful fabrication of loaded nanofibers with strong in vitro anti-bacterial and anti-oxidant activities. Furthermore, in vivo wound healing confirmed the potential of bioactive NF membranes in epithelialization and granulation tissue formation. The angiogenesis was greatly prompted by the bioactive NF membranes through expression of vascular endothelial growth factor (VEGF). Moreover, the proposed NF membrane successfully terminated the inflammatory cycle by downregulating the pro-inflammatory cytokines interleukin −6 (IL-6) and matrix metalloproteinases-9 (MMP-9). In vitro and in vivo studies revealed the proposed NF membrane is a promising dressing material for the healing of DW., Graphical abstract Image 1, Highlights • A modified loading strategy was employed for dual bioactive agents through electrospinning. • The nanofibers sustainedly released the two bioactive agents. • The fabricated bioactive membranes turned out to be biocompatible, antioxidant and antibacterial. • The proposed bioactive membranes have posesses the potential of healing diabetic wounds.

In this paper, the design and implementation of a dual bands power amplifier using gallium nitride (GaN) high electron mobility transistor (HEMT) is presented. A methodology of realizing Class F and Inverse Class F dual bands power amplifier output topology is proposed. With simulation and measurement verification, the dual bands power amplifier gets good performances in L band and S band, 1.4GHz and 2.1GHz respectively. At the P −2 point, the output powers are higher than 41.3dBm and 41.2dBm, and generate more than 72% and 69% drain efficiency in the two 200MHz operation bands. Simulation and measurement results agree well with each other, verified the concept and method proposed in the paper.

This study investigated the effects of Lactobacillus hilgardii (LH), alone or in combination with Lactobacillus plantarum (LP), on the aerobic stability, fermentation quality and dynamics of the bacterial and fungal communities of sugarcane top silage. Results demonstrated that LH and LHLP (LH combined with LP) improved the aerobic stability of sugarcane top silages. As the exposure time increased, the pH values and the contents of lactic acid, acetic acid, as well as propionic acid remained stable in silage treated with LH and LHLP. The abundance of L. hilgardii was enriched and the undesirable microorganisms, such as Acetobacter pasteurianus, Paenibacillus amylolyticus and yeasts like Kazachstania humilis, were suppressed in silages treated with LH and LHLP. In conclusion, LH-treated silage, whether with LP or not, positively impacted the fungal and bacterial microbes. This improved the quality of fermentation, the aerobic stability, and reduced aerobic spoilage in sugarcane top silage.

Gut microbiota-derived tryptophan metabolites such as indole derivatives are an integral part of host metabolome that could mediate gut&ndash, brain communication and contribute to host homeostasis. We previously reported that infant-type Human-Residential Bifidobacteria (HRB) produced higher levels of indole-3-lactic acid (ILA), suggesting the former might play a specific role in microbiota&ndash, host crosstalk by producing ILA in human infants. Nonetheless, the biological meaning of bifidobacteria-derived ILA in infant health development remains obscure. Here, we sought to explore the potential role of ILA in neuronal differentiation. We examined the neurite outgrowth and acetylcholinesterase (AchE) activity of PC12 cells following exposure to ILA and NGF induction. We found that ILA substantially enhanced NGF-induced neurite outgrowth of PC12 cells in a dose-dependent manner, and had the most prominent effect at 100 nM. Significant increases in the expression of TrkA receptor, ERK1/2 and CREB were observed in ILA-treated PC12 cells, suggesting ILA potentiated NGF-induced neurite outgrowth through the Ras/ERK pathway. Additionally, ILA was found to act as the aryl hydrocarbon receptor (AhR) agonist and evoked NGF-induced neurite outgrowth in an AhR-mediated manner. These new findings provide clues into the potential involvement of ILA as the mediator in bifidobacterial host&ndash, microbiota crosstalk and neuronal developmental processes.

Two new cadmium(II)-based materials, featuring two-dimensional (2D) [Cd2(&mu, 6-deta)(bpy)(H2O)]n (1) and three-dimensional (3D) [Cd2(&mu, 5-deta)(bpy)2(H2O)]n (2) structures, were constructed by the hydrothermal method from 2,3&prime, 4&prime, 5-diphenyl ether tetracarboxylic acid (H4deta) as an unexplored linker in research on coordination polymers (CPs) and 2,2&prime, bipyridine (bpy) as a mediator of crystallization. Microcrystalline samples of 1 and 2 were analyzed by IR/PXRD/EA/TGA and X-ray diffraction using single crystals. Structures and topologies of CPs 1 and 2 were established, revealing a 4,6L45 topological layer in 1 and a 3,5T1 topological framework in 2. Structural differences for 1 and 2 are attributed to distinct molar ratios between Cd2+ and bpy during the hydrothermal synthesis. Luminescence and thermal behavior of the obtained materials were also investigated. The present work opens up the use of an unexplored 2,3&prime, 5-diphenyl ether tetracarboxylic acid as a versatile and flexible linker toward the generation of functional coordination polymer materials.

SCOPE: We aimed at evaluating the effect of dietary ellagic acid (EA) and its microbial metabolite urolithin A (UA) on glucose metabolism and insulin resistance (IR) in mice with diet-induced IR. METHODS AND RESULTS: DBA2J mice were fed a high fat/high sucrose diet (HF/HS) for 8 weeks to induce IR and then 0.1% EA, UA, or EA and UA combined (EA+UA) were added to the HF/HS-diet for another 8 weeks. UA significantly decreased fasting glucose and increased serum adiponectin compared with HF/HS-controls. During intraperitoneal insulin tolerance test, EA+UA significantly improved insulin-mediated glucose lowering effects at 15 and 120 min and reduced blood triglycerides compared with HF/HS-controls. Serum free fatty acids were significantly decreased by EA, UA and EA+UA. We observed differential expression of genes related to mitochondrial function by EA, UA and EA+UA in liver and skeletal muscle. Primary hepatocytes from IR-mice had higher proton leak, basal and ATP-linked oxygen consumption rates compared with healthy controls. EA and EA+UA but not UA reduced the proton leak in hepatocytes from IR-mice. CONCLUSION: EA and UA induced different metabolic benefits in HF/HS diet induced IR mice. The effects of EA and UA on mitochondrial function suggest a potentially novel mechanism modulating metabolism. This article is protected by copyright. All rights reserved.

This study investigated the inhibitory effect of arctigenin, a novel anti-inflammatory lignan, on prostate cancer in obese conditions both in vitro and in vivo. In vitro obese models were established by co-culture of mouse adipocytes 3T3-L1 with androgen-sensitive LNCaP human prostate cancer cells, or by culturing LNCaP cells in adipocytes-conditioned medium. Arctigenin significantly inhibited LNCaP proliferation, along with decreased androgen receptor (AR) and increased Nkx3.1 cellular expression. Male severe combined immunodeficiency mice were subcutaneously implanted with human prostate cancer LAPC-4 xenograft tumors for in vivo study. Mice were fed high-fat (HF) diet and orally given arctigenin at 50 mg/kg body weight daily or vehicle control for 6 weeks. Tumor bearing HF control mice showed a significant increase in serum free fatty acids (FFAs) and decrease in subcutaneous/peritoneal fat depots compared to non-tumor bearing control mice. Arctigenin intervention significantly reduced tumor growth by 45%, associated with decreased circulating FFAs and adipokines/cytokines including IGF-1, VEGF, and MCP-1, along with decreased AR, Ki67, and microvessel density and increased Nkx3.1 expression in tumors. These results indicate the strong ability of arctigenin to co-target obesity and tumor itself in inhibition of prostate tumor growth at a lower concentration compared to most phytochemicals.

We recently proposed, and successfully applied, a novel and efficient technique-ultrasonic-circulating extraction (UCE) integrating superfine pulverization-to extract and prepare antioxidant crude polysaccharides other natural active substances from Ganoderma lucidum. The aim of this study was to evaluate the antioxidant and hepatoprotective activities and active ingredients in the powder from UCE (UCEP) through comparison with powder from hot water extraction (HWEP). The DPPH radical, ABTS radical, superoxide anion, total antioxidant activity, and ferric-reducing antioxidant power assay results showed that the UCEP exhibited stronger (P < 0.01) in vitro antioxidant activity than the HWEP. The hepatoprotective activity of the extracts was evaluated against CCl4-induced oxidative damage in the liver. Measurements of reduced glutathione, superoxide dismutase, and malondialdehyde in rat liver; measurements of alanine transaminase, aspartate transaminase, and lactate dehydrogenase in rat blood; and Western blotting for antioxidant proteins of transforming growth factor-β1, heme-oxygenase 1, and glutathione per-oxidase showed that the UCEP had antioxidant activity in vivo either similar to or slightly stronger than (P < 0.1) the HWEP. Further analysis of the active ingredients revealed that the UCEP and HWEP have similar mean yield and total triterpenoid content, but the former has significantly higher (P < 0.05) mean yield and total polysaccharide content than the latter. Our results suggest that the UCEP displays stronger antioxidant activities because of the larger amount of total polysaccharides; the UCEP may be able to be used as an antioxidant and liver protectant.

Accumulating evidence suggests a relationship between the gut microbiota and the development of obesity, indicating the potential of probiotics as a therapeutic approach. Bifidobacterium breve B-3 has been shown to exert anti-obesity effects in high-fat diet-induced obese mice. In the present study, the anti-obesity effects of the consumption of B. breve B-3 by healthy pre-obese (25 ≤ BMI < 30) adults were investigated in a randomized, double-blind, placebo-controlled trial (trial registration: UMIN-CTR No. 000023919; preregistered on September 2, 2016). Eighty participants were randomized to receive placebo or B. breve B-3 capsules (2 × 1010 CFU/day) daily for 12 weeks. The visceral fat area significantly increased at weeks 4 and 8 in the placebo group only; no significant change was observed in the B-3 group. Body fat mass and percent body fat were significantly lower in the B-3 group than in the placebo group at weeks 8 and 12 (p

Three new 2D lanthanide-organic networks, {[Sm-2(mu(4)-cpta)(mu(5)-cpta)(H2O)(3)]center dot 3H(2)O}(n) (1) and [Ln(mu(3)-cpta)(phen)(H2O)(2)](n) (Ln = Tb (2) and Sm (3)), were successfully synthesized via hydrothermal reactions using Ln(NO3)(3)center dot 6H(2)O, a flexible ether-bridged tricarboxylic acid H(3)cpta (2-(2-carboxyphenoxy)terephthalic acid) as a principal building block, and phen (1,10-phenanthroline) as an optional supporting ligand. All products were obtained as air and thermally stable microcrystalline solids and fully characterized by standard solid-state techniques, including elemental analysis, TGA, IR spectroscopy, powder and single-crystal X-ray diffraction. Compound 1 possesses an intricate 2D layer structure with the 4,5L51 topology, which is driven by the mu(4)- and mu(5)-cpta(3) and Sm(III) nodes. Compounds 2 and 3 are isostructural and disclose a different 2D metal-organic network with the fes topology, which is assembled from the mu(3)-cpta(3) and Ln(III) nodes. Luminescence properties of 2 and derived M(n+)2 suspensions were investigated, disclosing a possible use of this compound as a notable luminescence sensor for the detection of Fe3+ cations in aqueous medium. (C) 2017 Elsevier B.V. All rights reserved.

5-(3,4-Dicarboxylphenyl)picolinic acid (H3dppa) was applied as a novel tricarboxylic acid block with phthalate and picolinate functionalities for the aqueous-medium assembly of seven new coordination compounds, namely, [Mn2(μ-Hdppa)2(phen)2(H2O)2] (1), {[Mn(μ-Hdppa)(2,2′-H2biim)(H2O)]·H2O}n (2), [Ni(Hdppa)(phen)2]·4H2O (3), {[Ni(μ-Hdppa)(μ-4,4′-bipy)(H2O)]·H2O}n (4), {[Cu3(μ3-dppa)(μ-Hdppa)(phen)4]2[Cu(μ-Hdppa)2]·10H2O}n (5), {[Ni3(μ-dppa)2(μ-1,4-bpb)2(H2O)6]·4H2O}n (6), and {[Zn3(μ4-dppa)2(phen)2(H2O)2]·4H2O}n (7). These products 1–7 represent the first structurally characterized examples of the coordination compounds derived from H3dppa. Compounds 1–7 were assembled in the presence of various N-donor supporting ligands acting as crystallization mediators, which were selected from 1,10-phenanthroline (phen), 2,2′-biimidazole (H2biim), 4,4′-bipyridine (4,4′-bipy), or 1,4-bis(pyrid-4-yl)benzene (1,4-bpb). Full characterization of 1–7 by IR spectroscopy, thermogravimetric (TGA), elemental, and topological analyses, as well as powder (PXRD) and single-crystal X-ray diffraction, was performed. The structural types range from the discrete 0D complexes (1 and 3) and 1D coordination polymers with a 2C1 topology (2, 5, and 6) to the 2D metal–organic layers with an sql topology (4 and 7). The structural diversity of 1–7 is driven by various factors, including the metal(II) node nature, deprotonation degree of H3dppa, or type of crystallization mediator. The magnetic properties of 1, 2, 4, and 6 were studied and modeled, revealing antiferromagnetic (in 1, 2, and 6) or ferromagnetic (in 4) interactions between adjacent metal(II) centers. The luminescence of 7 was also investigated. Moreover, the photocatalytic activity of 1–7 was studied for the degradation of methylene blue as a model dye pollutant, disclosing that the nickel(II) coordination polymer 4 is the most active catalyst. The observed catalytic activity of 1–7 correlates well with their band gap energies determined by the UV-diffuse reflectance method.

OBJECTIVES: Inflammatory bowel disease (IBD) results from a complex interaction among host, microbial and environmental factors. Among these, diet has emerged as an important and actionable modifier of IBD activity. Pomegranate major bioactive metabolites, ellagic acid and urolithins, have been shown to improve symptoms of IBD in chemically induced mouse models of colitis. Here, we aim to test the hypothesis that dietary pomegranate extract (PomX) supplementation will reduce the development of colitis in IL-10 knock out (IL-10(−/−)) mice, which spontaneously develop chronic colitis after birth. METHODS: 4 week old male IL-10(−/−) mice were randomly assigned to a high fat high sucrose (HFHS) diet, or to a HFHS diet supplemented with 0.25% PomX for 8 weeks. At the end of the experiment, the mice were euthanized and intestinal tissues were isolated and frozen for RNA extraction, or fixed for histologic analysis. Plasma samples were collected and processed for lipocalin 2 assay. RESULTS: Histomorphological analysis of colonic tissues revealed lower histological scores in HFHS-PomX fed mice, 3.9 ± 1.0 vs. 2.6 ± 0.5 in HFHS fed mice (n = 8, P = 0.02). In addition, signs of rectal prolapse were observed in 62.5% of IL-10(−/−) mice in the HFHS group vs. 12.5% in the HFHS/PomX group (P = 0.04). RNAseq and bioinformatic analysis, obtained from the colonic tissues (n = 4 mice/each group), showed in PomX treated mice a downregulation of 483 genes and an upregulation of 263 genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome analyses showed that PomX downregulated genes which are mainly associated with immune inflammatory responses, defenses, and neutrophil degranulation, including IL1α, IL6 and TNFα pro-inflammatory cytokines. Spleen weights were lower in HFHS-PomX treated mice as compared to HFHS fed control mice (P = 0.04). In addition, PomX treated mice showed a trend of higher body weights (∼13%) and lower lipocalin 2 plasma levels (∼46%) as compared to HFHS fed mice. CONCLUSIONS: Our data demonstrated that PomX supplementation decreased colitis symptoms and lowered the inflammatory parameters of colitis in HFHS fed IL10(−/−) mice. These data support the anti-inflammatory effects of dietary PomX supplementation that were previously observed in the DSS colitis murine model. FUNDING SOURCES: This project was supported by UCLA Center for Human Nutrition.

Biphenyl-2,5,3′-tricarboxylic acid (H3L) was selected as an unexplored tricarboxylate building block and applied for the hydrothermal synthesis of three novel coordination compounds, namely a 0D tetramer [Co4(HL)2(μ3-HL)2(phen)6(H2O)2]·3H2O (1) and two 3D metal-organic frameworks (MOFs) [Cd3(μ5-L)(μ6-L)(py)(μ-H2O)2(H2O)]n·H2O (2) and [Zn3(μ4-L)2(2,2′-bpy)(μ-4,4′-bpy)]n·2H2O (3). These products were easily generated in aqueous medium from the corresponding metal(II) chlorides, H3L, and various N-donor ancillary ligands, selected from 1,10-phenanthroline (phen), pyridine (py), 2,2′-bipyridine (2,2′-bpy), and 4,4′-bipyridine (4,4′-bpy). Compounds 1–3 were isolated as stable crystalline solids and were fully characterized by IR and UV–vis spectroscopy, elemental, thermogravimetric (TGA), powder (PXRD) and single-crystal X-ray diffraction analyses. Compound 1 possesses a discrete tetracobalt(II) structure, which is extended into a 3D H-bonded network with the pcu topology. In contrast, MOF 2 discloses a very complex trinodal 4,5,12-connected net with an undocumented topology, while MOF 3 features the nce/I topological framework. The magnetic (for 1) and luminescence (for 2 and 3) properties were also studied and discussed. The present study thus widens a still very limited family of metal-organic and supramolecular frameworks driven by flexible biphenyl-2,5,3′-tricarboxylate building blocks.

We previously reported that lysozyme present in breast milk is a selection factor for bifidobacterial colonization in infant human intestines. This study is aimed at examining their underlying mechanisms. Human-residential bifidobacteria (HRB) generally exhibited higher tolerance than non-HRB to lysozymes, except B. bifidum subspecies. To assess the involvement of enzymatic activity of lysozyme, peptidoglycan (PG) was isolated and the degree of O-acetylation (O-Ac) in 19 strains, including both HRB and non-HRB, was determined. Variety in the degree of O-Ac was observed among each of the Bifidobacterium species; however, all purified PGs were found to be tolerant to lysozyme, independent of their O-Ac degree. In addition, De-O-Ac of PGs affected the sensitivity to lysozyme of only B. longum-derived PG. To examine the non-enzymatic antibacterial activity of lysozyme on bifidobacteria, lysozyme was heat-denatured. The HRB and non-HRB strains exhibited similar patterns of susceptibility to intact lysozyme as they did to heat-denatured lysozyme. In addition, strains of B. bifidum (30 strains), which showed various tolerance of lysozyme, also exhibited similar patterns of susceptibility to intact lysozyme as they did to heat-denatured lysozyme. These results suggest that bifidobacteria are resistant to the peptidoglycan-degrading property of lysozyme, and the tolerance to lysozyme among some HRB strains is due to resistance to the non-enzymatic antibacterial activity of lysozyme.

The objective was to study effects of lactic acid bacteria (L) and molasses (M) on the microbial community and fermentation quality of soybean silage. Soybean was ensiled with no additive control (C), 0.5% molasses (0.5%M), 0.5%M+L (0.5%ML), 2%M, 2%M+L (2%ML) for 7, 14, 30 and 60days. The M-treated silages could increase the content of lactic acid and decrease butyric acid than control. Besides, higher crude protein was also observed in M-treated silages. With prolonged ensiling time, there was a reduction of the ratio of lactic acid/acetic acid in the 2%M-treated and 2%ML-treated silages. The combined addition of L and 2%M could enhance the account of desirable Lactobacillus and inhibit the growth of undesirable microorganism such as Clostridia and Enterobacter. In summary, the silage quality of soybean was improved with the addition of L and M.

Ethnopharmacological relevance The roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously. Aim of the study This work was carried out to investigate the anticancer and anti-angiogenic activities of AER. Materials and methods The growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A. eriantha on human gastric carcinoma SGC7901 cells, human nasopharyngeal carcinoma CNE2 cells, human breast carcinoma MCF7 cells and human umbilical vein endothelial cells (HUVECs) were evaluated by MTT assay. The ethyl acetate fraction from EER (EA-EER) was further investigated for the anticancer activity against SGC7901 cells and the anti-angiogenic activity in HUVECs in vitro . The apoptosis in SGC7901 cells and HUVECs was confirmed by DAPI nuclear staining and flow cytometry analysis, the effect on cellular DNA fragmentation was detected in SGC7901 cells. And the cell cycle-arresting activity in HUVECs was determined by flow cytometry. Moreover, the inhibitory effect of EA-EER on cell migration in HUVECs was observed by both wound-healing and Transwell migration assays. RT-PCR and Western-blotting were performed to determine the mRNA and protein expression levels, respectively, including Bax, Bcl-2 and caspase-3 in SGC7901 cells, as well as VEGF-A and VEGFR-2 in HUVECs. Furthermore, the in vivo anti-angiogenic activity of EA-EER was evaluated by using chick embryo chorioallantoic membrane (CAM) assay. Ultimately, the chemical components in EA-EER were isolated and purified by repeated column chromatography followed by structure characterization using 1 H and 13 C nuclear magnetic resonance and mass spectroscopy. Results Compared with EEL and EES, EER displayed the strongest growth inhibitory effect on SGC7901 cells, CNE2 cells and HUVECs. Among the EER fractions, EA-EER exhibited the most potent growth inhibitory activity against SGC7901 cells, CNE2 cells and HUVECs. Moreover, EA-EER induced obvious apoptosis in SGC7901 and HUVECs, and significantly inhibited the proliferation of HUVECs via blockade of cell cycle G1 to S progression. Furthermore, EA-EER suppressed the expression of Bcl-2 and improved the expression Bax and caspase-3 in SGC7901 cells. EA-EER not only inhibited migration of HUVECs, but also down-regulated the expression of VEGF-A and VEGFR-2 in HUVECs. In vivo, EA-EER exposure reduced the formation of blood vessels in chick embryos. A bio-guided isolation of EA-EER led to the isolation of three compounds for the first time, namely (6R, 7E, 9S)-6, 9-hydroxy-megastigman-4, 7-dien-3-one-9-O-β- D -glucopyranoside, Oleanolic acid-23-O-β- D -glucopyranoside, 3β, 23, 24-trihydroxyl-12-oleanen-28-oic acid. Conclusion The present research demonstrated that the significant anticancer and anti-angiogenic effects of AER, providing the supportive evidence for its traditional use in the treatment for cancer. It was suggested that AER could be use as a potential source of cancer therapeutic drug.

The development of direct-acting antivirals (DAAs) has significantly improved hepatitis C virus (HCV) treatment. However, drug resistance remains a potential concern in the real-world DAA-based therapies. We previously developed a novel full-length genotype 2a HCVcc clone PR63cc directly from clinical isolates. Here in this study, we compared the sensitivity of PR63cc and JFH1 to 12 different DAAs most of which are either already in clinical use or in the late clinical development phase. For NS5B inhibitors, PR63cc and JFH1 displayed comparable sensitivity to nucleoside/nucleotide analogues sofosbuvir and 2'-C-methyladenosine, while PR63cc was 4-fold more sensitive than JFH1 to nesbuvir, a non-nucleoside inhibitor. Interestingly, PR63cc and JFH1 were both completely resistant to dasabuvir which efficiently inhibited the replication of genotype 1b HCV replicon. For NS5A inhibitors, while PR63cc was as sensitive as JFH1 to ombitasvir and velpatasvir, it was much more resistant than JFH1 to daclatasvir and ledipasvir, which was mainly due to methionine at amino acid residue 31 of NS5A. For NS3 inhibitors, PR63cc was generally less sensitive than JFH1 to simeprevir, grazoprevir, asunaprevir and paritaprevir. Serine at residue 67 of NS3 was identified to be a resistance-associated variant (RAV) for asunaprevir. Finally, we showed that PR63cc was more resistant than JFH1 to the asunaprevir/daclatasvir combination treatment. In summary, our study systemically analyzed the DAA sensitivity of a new HCVcc strain and identified critical RAVs. These results are not only important for monitoring the emergence of drug-resistant mutations of current DAA therapies, but also valuable for developing next-generation DAAs.

4-(3-Carboxyphenyl)picolinic acid (H2cppa) was applied as a new and virtually unexplored building block for the synthesis of eleven new coordination compounds, namely [M(Hcppa)2(H2O)2]·2H2O {M = Ni (1) and Zn (2)}, [M(μ3-cppa)(H2O)2]n {M = Ni (3) and Co (4)}, {[Co(μ-cppa)(2,2′-bipy)(H2O)]·H2O}n (5), [Zn(μ-cppa)(2,2′-bipy)]n (6), [M(μ-cppa)(phen)(H2O)]n {M = Co (7), Zn (8), Mn (9), and Cu (10)}, and {[Cd3(μ3-cppa)3(phen)2]·4H2O}n (11). All these compounds were generated by a hydrothermal self-assembly method using the corresponding metal(II) chlorides, H2cppa, and two types of N-donor ancillary ligands, selected from 2,2′-bipyridine (2,2′-bipy) or 1,10-phenanthroline (phen). The obtained products 1–11 were characterized by standard methods, including IR spectroscopy, elemental and thermogravimetric analyses, and powder and single-crystal X-ray diffraction. They represent the first structurally characterized compounds derived from H2cppa. The structures of 1–11 vary from a complex 3D metal–organic framework (MOF) 11 to 2D coordination polymers 3 and 4, 1D coordination polymers 5–10, and discrete 0D monomers 1 and 2. Such a structural diversity is guided by the nature of the metal(II) node, level of deprotonation of 4-(3-carboxyphenyl)picolinic acid, and type of applied ancillary ligand. In addition, the structures of 1, 2, 5, and 7–10 are further extended [0D → 3D (1 and 2), 1D → 2D (5), and 1D → 3D (7–10)] into various H-bonded supramolecular networks. Both the supramolecular (in 1, 2, 5, and 7–10) and metal–organic (in 3, 4, 6, and 11) underlying networks were analyzed and classified from the topological viewpoint, revealing the distinct pcu (in 1 and 2), fes (in 3 and 4), gek1 (in 5), 2C1 (in 6), and srs (in 7–10) topological nets, whereas a topologically unique framework was identified in MOF 11. The magnetic behavior of 3–5, 7, 9, and 10 and luminescence properties of 2, 6, 8, and 11 were also investigated and discussed.

In this work, a trifunctional N,O-building block, 5-(4-carboxyphenoxy)nicotinic acid (H2cpna), that combines three distinct types of functional groups (COOH, N-pyridyl, and O-ether) was used for the hydrothermal assembly of thirteen new coordination compounds: [Co(μ3-Hcpna)2]n (1), [Mn(μ4-cpna)(H2O)]n (2), [Mn(μ4-cpna)(H2O)2]n (3), [Mn(μ-cpna)(2,2'-bipy)(H2O)2]n (4), {[Ni(μ3-cpna)(2,2'-bipy)(H2O)]2·H2O}n (5), {[Cd(μ3-cpna)(2,2'-bipy)]·2H2O}n (6), [Zn2(μ-cpna)2(2,2'-bipy)2] (7), [Cu(μ-cpna)(2,2'-bipy)(H2O)]n (8), {[Mn(μ-cpna)(phen)2]·6H2O}n (9), {[Ni(μ3-cpna)(phen)(H2O)]·H2O}n (10), [Zn2(μ-cpna)2(phen)2] (11), {[Pb(μ3-cpna)(phen)]·H2O}n (12), and [Ni(μ3-cpna)(4,4'-bipy)0.5(H2O)]n (13). These products were synthesized from the corresponding metal(ii) chlorides, H2cpna, NaOH, and optional N-donor supporting ligands or templates {bis(4-pyridyl)amine (bpa), 2,2'-bipyridine (2,2'-bipy), 4,4'-bipyridine (4,4'-bipy), or 1,10-phenanthroline (phen)}. Products 1-13 were characterized in the solid state by standard methods, including elemental and thermogravimetric analysis (TGA), IR spectroscopy, and powder (PXRD) and single-crystal X-ray diffraction. The structures of 1-13 feature distinct structural types, namely the 3D metal-organic frameworks (MOFs 1-3), the 2D coordination polymers (5, 6, 10, 12, and 13), the 1D coordination polymers (4, 8, and 9), and the 0D discrete cyclic dimers (7 and 11). Such a wide structural diversity of 1-13 is driven by various factors, including the type of the metal(ii) node, the deprotonation degree of H2cpna, and/or the type of supporting ligand or template. Notably, an addition of bpa can tune the structure of MOF 3 by the template effect. Topological classification of underlying metal-organic networks was performed, leading to several distinct topological nets: rtl (in 1), hxg-d-4-C2/m (in 2), sra (in 3), 2C1 (in 4, 8 and 9), fes (in 5, 10, and 12), hcb (in 6), and 3,4L83 (in 13). The magnetic behavior of 1-5, 8-10, and 13 was studied and theoretically modeled, disclosing antiferromagnetic interactions. The luminescence behavior of 6, 7, 11, and 12 was also investigated.

The cardiovascular diseases (CVD) associated with the highest rates of morbidity are coronary heart disease and stroke, and the primary etiological factor leading to these conditions is atherosclerosis. This long-lasting inflammatory disease, characterized by how it affects the artery wall, results from maladaptive immune responses linked to the vessel wall. Tryptophan (Trp) is oxidized in a constitutive manner by tryptophan 2,3-dioxygenase in liver cells, and for alternative cell types, it is catalyzed in the presence of a differently inducible indoleamine 2,3-dioxygenase (IDO1) in the context of a specific pathophysiological environment. Resultantly, this leads to a rise in the production of kynurenine (Kyn) metabolites. Inflammation in the preliminary stages of atherosclerosis has a significant impact on IDO1, and IDO1 and the IDO1-associated pathway constitute critical mediating agents associated with the immunoinflammatory responses that characterize advanced atherosclerosis. The purpose of this review is to survey the recent literature addressing the kynurenine pathway of tryptophan degradation in CVD, and the author will direct attention to the function performed by IDO1-mediated tryptophan metabolism.

In this work, an ether-bridged aromatic carboxylic acid, 2-(2-carboxyphenoxy)terephthalic acid (H3cpta), was applied as an unexplored building block for the generation of a novel series of coordination compounds, which represent the first examples of structurally characterized products derived from H3cpta, thus opening up its use as a versatile building block in crystal engineering research. The obtained products were formulated as [Cd(μ-Hcpta)(phen)(H2O)]n (1), [Mn(μ-Hcpta)(phen)(H2O)]n (2), {[Cd3(μ3-Hcpta)(μ4-cpta)(μ-Cl)(H2O)4]·2H2O}n (3), {[Cd3(μ6-cpta)2(py)2]·5H2O}n (4), [Mn3(μ5-cpta)2(2,2′-bipy)2]n (5), [Mn3(μ4-cpta)2(phen)3(H2O)2]n (6), {[Zn3(μ3-cpta)2(phen)3]·3H2O} (7), [Cd2(μ4-cpta)(μ-Cl)(phen)2]n (8), [Cd3(μ5-cpta)2(phen)2(H2O)2]n (9), [Cd3(μ4-cpta)2(phen)3(H2O)2]n (10), [Cd3(μ5-cpta)2(H2biim)2]n (11), [Zn2(μ6-cpta)(μ-Hbiim)]n (12), and [Ni3(μ3-cpta)2(phen)3(py)3(H2O)3]n (13). These compounds were assembled in the presence of an optional N-donor ancillary ligand, which was selected from 1,10-phenanthroline (phen), pyridine (py), 2,2′-bipyridine (2,2′-bipy), or 2,2′-biimidazole (H2biim). The obtained compounds 1–13 were fully characterized, including by IR spectroscopy, elemental analysis, thermogravimetric analysis (TGA), powder (PXRD) and single-crystal X-ray diffraction. The structures of 1–13 vary from a discrete 0D dimer (1) to the 1D (2, 3, 7, and 13) and 2D (5, 6, and 8–11) coordination polymers, as well as to the 3D metal–organic frameworks (MOFs 4 and 12). Such a wide structural diversity of 1–13 is guided by the following factors: a type of metal(II) node and counter anion, a deprotonation degree of the principal H3cpta block, and/or a type of an auxiliary ligand. Topological classification of H-bonded (in 1) and metal–organic (in 2–13) underlying networks was performed, disclosing the following topological types: sql (in 1), 2C1 (in 2 and 7), 3,4,5L45 (in 5, 9, and 11), 3,4L128 (in 6 and 10), 3,3,4L29 (in 8), and SP 1-periodic net (in 13), as well as some topologically unique nets (in 3, 4, and 12). Besides, magnetic properties of 2, 5, 6, and 13 were studied and modeled, revealing antiferromagnetic interactions between adjacent metal(II) centers. In addition, luminescence properties were investigated for 1, 3, 4, and 7–12; MOF 4 can be used as a sensitive material for the detection of Fe3+ ions in aqueous solution through the luminescence quenching effect.

Lactobacillus plantarum is a versatile bacterium with significant adaptability to harsh habitats containing excessive ethanol concentrations. It was found that the L. plantarum NF92-TetR/AcrR family regulator, AcrR, significantly enhanced the growth rate of this lactic acid bacterium in the presence of ethanol. Through screening 172 ethanol-resistant related genes by electrophoretic mobility shift and quantitative reverse transcription-PCR (RT-qPCR) assays, six genes were identified to be regulated by AcrR under ethanol stress. Among these was a gene coding for a 3-hydroxyacyl-ACP dehydratase (fabZ1) regulated by AcrR under ethanol stress. AcrR regulated fabZ1 under ethanol stress by binding to its promoter, P(fabZ1). DNase I footprinting analysis indicated that there were two specific AcrR binding sites on P(fabZ1). RT-PCR results showed fabZ1 could cotranscribe with its downstream 12 genes and conform a fatty acid de novo biosynthesis (fab) gene cluster under the control of P(fabZ1). Both RT-qPCR of the fab gene cluster in acrR knockout and overexpression strains and fatty acid methyl ester analysis of the acrR knockout strain showed that AcrR could promote fatty acid synthesis in L. plantarum NF92. Membrane fluorescence anisotropy analysis of acrR knockout and overexpression strains showed that AcrR could increase membrane fluidity under ethanol stress. Thus, AcrR could regulate fatty acid synthesis and membrane fluidity to promote the adaption of L. plantarum NF92 to a high ethanol concentration. IMPORTANCE Ethanol tolerance is essential for L. plantarum strains living in substances with more than 9% ethanol, such as wine and beer. The details regarding how L. plantarum adapts to ethanol are still lacking. This study demonstrates that AcrR regulates the de novo synthesis of fatty acids in L. plantarum adapting to toxic levels of ethanol. We also identified the ability of the TetR/AcrR family regulator to bind to the fatty acid biosynthesis gene promoter, P(fabZ1), in L. plantarum and defined the binding sites. This finding facilitates the induction of the adaptation of L. plantarum strains to ethanol for food fermentation applications.

Furfural is an important renewable precursor for multiple commercial chemicals and fuels; a main inhibitor existing in cellulosic hydrolysate, which is used for bioethanol fermentation; and a potential carcinogen, as well. Using a genetic system in Saccharomyces cerevisiae that allows detection of crossover events, we observed that the frequency of mitotic recombination was elevated by 1.5- to 40-fold when cells were treated with 0.1 g/liter to 20 g/liter furfural. Analysis of the gene conversion tracts associated with crossover events suggested that most furfural-induced recombination resulted from repair of DNA double-strand breaks (DSBs) that occurred in the G1 phase. Furfural was incapable of breaking DNA directly in vitro but could trigger DSBs in vivo related to reactive oxygen species accumulation. By whole-genome single nucleotide polymorphism (SNP) microarray and sequencing, furfural-induced genomic alterations that range from single base substitutions, loss of heterozygosity, and chromosomal rearrangements to aneuploidy were explored. At the whole-genome level, furfural-induced events were evenly distributed across 16 chromosomes but were enriched in high-GC-content regions. Point mutations, particularly the C-to-T/G-to-A transitions, were significantly elevated in furfural-treated cells compared to wild-type cells. This study provided multiple novel insights into the global effects of furfural on genomic stability. IMPORTANCE Whether and how furfural affects genome integrity have not been clarified. Using a Saccharomyces cerevisiae model, we found that furfural exposure leads to in vivo DSBs and elevation in mitotic recombination by orders of magnitude. Gross chromosomal rearrangements and aneuploidy events also occurred at a higher frequency in furfural-treated cells. In a genome-wide analysis, we show that the patterns of mitotic recombination and point mutations differed dramatically in furfural-treated cells and wild-type cells.

Recent studies have shown that metabolites produced by microbes can be considered as mediators of host-microbial interactions. In this study, we examined the production of tryptophan metabolites by Bifidobacterium strains found in the gastrointestinal tracts of humans and other animals. Indole-3-lactic acid (ILA) was the only tryptophan metabolite produced in bifidobacteria culture supernatants. No others, including indole-3-propionic acid, indole-3-acetic acid, and indole-3-aldehyde, were produced. Strains of bifidobacterial species commonly isolated from the intestines of human infants, such as Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Bifidobacterium bifidum, produced higher levels of ILA than did strains of other species. These results imply that infant-type bifidobacteria might play a specific role in host−microbial cross-talk by producing ILA in human infants.