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Background The biofilm state of pathogens facilitates antimicrobial resistance which makes difficult-to-treat infections. In this regard, it has been found that the compounds screened from plant extracts represent one category of the most promising antibiofilm agents. However, the antibiofilm activities and the active ingredients of plant extracts remain largely unexplored. In this background, the study is (1) to screen out the plant extracts with antibiofilm ability against Pseudomonas aeruginosa, and (2) to identify the active ingredients in the plant extracts and elucidate the underlying mechanism of the antibiofilm activities. Methods Micro-broth dilution method, in vitro biofilm model, LC–MS/MS analysis and P. aeruginosa-mouse infection model were adopted to assess the antibiofilm activity. GC–MS analysis was performed to detect the active ingredients in plasma. RNA-Seq, GO analysis, KEGG analysis and RT-qPCR were adopted to elucidate the underlying mechanism of antibiofilm activities against P. aeruginosa. Results Lonicerae Japonicae Flos (LJF) among 13 plants could exert significant inhibitory effects on bacterial biofilm formation, mobility and toxin release in vitro, and it could exert antibiofilm effect in vivo too. Moreover, quinic acid, as one metabolite of chlorogenic acid, was found as an active ingredient in LJF against the biofilm of P. aeruginosa. The active ingredient significantly inhibited EPS secretion in biofilm formation and maturity and could achieve synergistic antibiofilm effect with levofloxacin. It reduced the biofilm formation by regulating core targets in quorum sensing system. In GO process, it was found that the core targets were significantly enriched in multiple biological processes involving locomotion, chemotaxis and motility mediated by flagellum/cilium, which was related to KEGG pathways such as bacterial chemotaxis, oxidative phosphorylation, ribosome, biofilm formation, cyanoamino acid metabolism and quorum sensing. Finally, the binding of quinic acid with core targets rhlA, rhlR and rhlB were validated by molecular docking and RT-qPCR. Conclusions In summary, the study verified the in vitro and in vivo antibiofilm effects of LJF against P. aeruginosa and elucidated the active ingredients in LJF and its conceivable pharmacological mechanism, indicating that quinic acid could have the potential of an antibiofilm agent against P. aeruginosa and related infections. Graphic abstract

Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.

An effective regiodivergent synthesis toward 1- and 3-thiosugars was achieved through palladium and cobalt catalysis, respectively. β-1-Thiosugars were obtained from 3,4-O-carbonate-glycals and var...

Atomically thin two-dimensional molybdenum disulfide (MoS2) is well known for its excellent lubrication characteristics and is usually used as a solid lubricant in diverse micro/nanoelectromechanical systems (MEMS/NEMS). The friction on atomically thin MoS2 deposited on a SiO2/Si substrate is reduced almost five times to achieve an ultra-low friction state (coefficient of friction nearly 0.0045) by rubbing the surface with an AFM tip under the electric field. The electric field leads to a shift and accumulation of charges at the interface between MoS2 and the SiO2/Si substrate. Then, electronic tight-binding with high interfacial bonding strength is experimentally found by the charges transferring during the rubbing process. The ultra-low friction state of atomically thin MoS2 could attribute to the electronic tight-binding between MoS2 and the SiO2/Si substrate, which suppresses the atomic-scale deformation and limits the local pinning capability of MoS2. The ultra-low friction state on atomically thin MoS2 is patterned further by controllably regulating position, time, and electric field during the rubbing process. This approach can provide an additional channel to achieve ultra-low friction on MoS2 related two-dimensional materials with semiconductor properties. The nanopatterning of ultra-low friction could promote and expand engineering applications of MoS2 as lubricants in various MEMS/NEMS with nano-scale components.

Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3-arylisoquinolones 3 h [3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxyisoquinolin-1(2H)-one] and 4 a [3-(4-(benzyloxy)-3-methoxyphenyl)-4-bromo-7,8-dimethoxyisoquinolin-1(2H)-one] were found to have potent inhibitory effects on hCES2A (IC50 =0.68 μΜ, Ki =0.36 μΜ) and excellent specificity (more than 147.05-fold over hCES1 A). Moreover, 4 a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3 h, with an IC50 value of 0.41 μΜ. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3 h and 4 a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure-activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.

Background The most common chemotherapeutic drug for triple-negative breast cancer (TNBC) treatment is 5-fluorouracil (5-FU), but its therapeutic index is low due to its toxicity. β-Elemene (ELE) possesses antitumor activity against different cancers, but it has never been used in combination with 5-FU to improve its chemotherapeutic effect against TNBC. Materials and methods We treated MDA-MB-231 and BT549 cells of TNBC with ELE alone, 5-FU alone, or their combination to investigate their treatment effects on cell viability, proliferation, migration, invasion, and colony formation. We verified the molecular mechanisms of our results through confocal immunofluorescence, immunohistochemistry, and Western blot analysis in vitro and in vivo. Results Our result revealed that ELE enhanced the 5-FU effect against cell viability, proliferation, migration, invasion, and colony formation through different mechanisms in MDA-MB-231 and BT549 cell lines. In molecular mechanisms, ELE and 5-FU in combination enhances apoptosis in both cell lines through Bl-2 family protein and caspase cascade modulation, thereby inhibiting NF-kB pathway through IKKβ, IKKα, and p65 downregulation in the cytoplasm and p50 and p65 downregulation in the nucleus. ELE and 5-FU in combination regulated the PI3K/AKT pathway through p-AKT, P-85, p110r, p-PDK1, and p110a protein and RAF-MEK-ERK pathway inhibition through the p-c-raf and p-ERK downregulation. The PI3K inhibitor LY294002 or RAF-MEK-ERK inhibitor U0126 in combination with ELE and 5-FU decreased cell viability in both cell lines significantly, thereby showing the involvement of these pathways in cell apoptosis. In mouse xenograft model, ELE and 5-FU in combination inhibited the tumor growth and modulated its molecular markers. Conclusion The conclusion obtained, considering that the results suggest that the combination may be important specifically in the treatment of TNBC.

A pair of new phenolic bisabolane-type sesquiterpenoid enantiomers (±)- phomoterpenes A and B [(±)-1] and two known analogues (2 and 3), together with two new isocoumarins, phomoisocoumarins C‒D (4‒5), were isolated from an endophytic fungus Phomopsis prunorum (F4-3). Their structures were elucidated by comprehensive spectroscopic analysis. The enantiomeric separation for (±)-1 were achieved by chiral-HPLC, and their absolute configurations were assigned by electronic circular dichroism (ECD) calculation. Compounds (+)-1 and 5 exhibited moderate antibacterial activity against plant pathogenic bacteria Pseudomonas syringae pv. Lachrymans with MIC values of 15.6 μg/mL.

A new methodology of stereoselective C-glycosylation has been developed with 3,4-O-carbonate glycals and boronic acids, catalyzed by 1,2-bis(phenylsulfinyl)ethane palladium(II) acetate under open-air conditions at room temperature. This mild method is simple in operation, wide in substrate range, and tolerant in alcoholic/phenolic hydroxyl and amino groups. High to excellent yields were observed for all substrates tested, with the driving force mainly contributed by decarboxylation. Meanwhile, the high 1,4-trans-selectivity was achieved by steric effects as proposed.

Currently, best-characterized indicators for Alzheimer's disease (AD) diagnosis are the decreased levels of amyloid-β protein 42 and increased levels of phosphorylated tau in cerebrospinal fluid (CSF). The positron emission tomography (PET) imaging with Pittsburgh compound B (PiB) is also used in AD diagnosis by visualizing amyloid deposition in the brain. These methods are invasive or expensive; therefore, less invasive and easily detectable blood biomarkers are required. Because our previous study showed that flotillin release, a marker of exosomes, was attenuated by Aβ, we designed the present study to determine whether flotillin level could be reduced in CSF and/or serum of patients with AD. In this study, we analyzed flotillin levels in CSF and serum of non-AD controls, patients with AD and mild cognitive impairment (MCI) by western blotting. Flotillin levels in cerebroventricular fluid (CVF) and serum of AD, vascular dementia (VaD), and non-AD autopsy cases were also analyzed. Flotillin levels significantly decreased in the CSF and serum of AD patients compared with those of non-AD controls, respectively. Moreover, in patients with MCI due to AD determined by PiB-PET, CSF and serum flotillin levels significantly decreased compared with those of patients with MCI due to non-AD. Flotillin levels remained unchanged in CVF and serum of autopsy cases diagnosed as VaD. Serum flotillin level is negatively associated with brain amyloid deposition indicated as PiB uptake. These results demonstrate that serum flotillin level can serve as one of the blood markers for estimation of brain amyloid deposition and early diagnosis of AD.

Exosomes are vesicles secreted by various kinds of cells, and they are rich in cholesterol, sphingomyelin (SM), phosphatidylcholine, and phosphatidylserine. Although cellular sphingolipid-mediated exosome release has been reported, the involvement of other lipid components of cell membranes in the regulation of exosome release is poorly understood. Here, we show that the level of exosome release into conditioned media is significantly reduced in cultured astrocytes prepared from apolipoprotein E (ApoE) knock-out mice when compared to those prepared from wild-type (WT) mice. The reduced level of exosome release was accompanied by elevated levels of cellular cholesterol. The addition of cholesterol to WT astrocytes significantly increased the cellular cholesterol levels and reduced exosome release. PI3K/Akt phosphorylation was enhanced in ApoE-deficient and cholesterol-treated WT astrocytes. In contrast, the depletion of cholesterol in ApoE-deficient astrocytes due to treatment with β-cyclodextrin recovered the exosome release level to a level similar to that in WT astrocytes. In addition, the reduced levels of exosome release due to the addition of cholesterol recovered to the control levels after treatment with a PI3K inhibitor (LY294002). The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.

The separation and chemical analysis of mixtures in an emergency situation represent major challenges, especially in remote or poverty-stricken areas. A novel method was developed for the rapid separation and detection of multiple components via paper centrifugal chromatography, which costs as little as $2.26 US. The method was realized based on the combination of portable paper centrifugal chromatography and surface-enhanced Raman scattering (SERS) detection. This coupled technique was successfully implemented for the separation and qualitative analysis of a rhodamine 6G-crystal violet mixture and a colorless aniline-pyrocatechol-benzidine mixture. A chromatographic mobile phase was collected using absorbent cotton, which was demonstrated to have no effect on the SERS results. The optimized device achieved rapid and effective separation of the colorless aniline-pyrocatechol-benzidine mixture with a high centrifugal force (0.3303π2 N). The newly developed method involving multicomponent paper centrifugal chromatography-SERS detection will be of great value for emergency-related substance separation and analysis in remote and poor areas.

Background: In cancers, tumor-associated macrophages (TAMs) play an important role in the progression, evasion of immunity and sensitivity to therapy. Unfortunately, radiation and hypoxia could induce the M2 macrophages infiltration and polarization. Materials and methods: In this study, we investigated the relevance of macrophage recruitment with radiation and hypoxia by transwell. We also evaluated the effect of β-elemene on the infiltration of M2 macrophages and explored its underlying molecular mechanism by a series of in vitro and in vivo experiments. Results: Irradiated or hypoxia lung cancer cells recruit macrophages, and the recruitment is MCP-1 dependent. We also found that radiation and hypoxia-induced MCP-1 secretion follows upregulation of Prx-1, which leads to nuclear accumulation of NF-κB and HIF-1α expression. In addition, β-elemene could effectively suppress this recruitment phenomenon through Prx-1/NF-κB/HIF-1α signaling. Conclusion: Our study showed that radiation and hypoxia significantly promoted the macrophages recruitment. β-elemene could effectively suppress this recruitment phenomenon and MCP-1 expression via inhibiting Prx-1/NF-κB/HIF-1α pathways.

The high cell density culture of baker's yeast FX-2 was investigated in a 50 L(A) automatic bioreactor. Herein, it was found firstly that the Crabtree effect clearly existed in batch fermentation with higher glucose content, then the critical initial glucose content range (≤2.00 g L-1 ) was reasonably ascertained to effectively avoid Crabtree effect. In the next fed-batch fermentations with different strategies, the second strategy (maintain ethanol concentration lower than 0.10% and pH around 4.80) was confirmed to be more beneficial to yeast growth than the first strategy (keep reducing sugar not more than 2.00 g L-1 and control steady Carbon/Nitrogen ratio 3.05:1.00). After that, one optimal control strategy (maintain pH around 4.80 and keep respiratory quotient in the range of 0.90-1.00) was constructed to further enhance cell yield. Under an optimal control strategy, four schemes with the aim of achieving pH-stat were compared, and yeast extract instead of other alkaline materials was selected as a better regulator. As a result, 148.37 g L-1 dry cell weight, 38.25 × 108 mL-1 living cells, and 8.24 g L-1 h-1 productivity were harvested, which respectively elevated 23.74%, 135.38%, and 24.47% compared to that obtained under the traditional scheme (regulate pH with ammonia); meanwhile, the maximum oxygen uptake rate and carbon dioxide excretion rate were both more than 250.00 mmol L-1 min-1 .

Background ErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As a membrane-embedded receptor tyrosine kinase, cell surface levels of ErbB2 are regulated dynamically by membrane physical properties. The present study aims to investigate the influence of membrane cholesterol contents on ErbB2 status and cellular responses to its tyrosine kinase inhibitors. Methods The cholesterol abundance was examined in ErbB2-positive breast cancer cells using filipin staining. Cellular ErbB2 localizations were investigated by immunofluorescence with altered membrane cholesterol contents. The inhibitory effects of the cholesterol-lowering drug lovastatin were assessed using cell proliferation, apoptosis, immunoblotting and immunofluorescence assays. The synergistic effects of lovastatin with the ErbB2 inhibitor lapatinib were evaluated using an ErbB2-positive breast cancer xenograft mouse model. Results Membrane cholesterol contents positively correlated with cell surface distribution of ErbB2 through increasing the rigidity and decreasing the fluidity of cell membranes. Reduction in cholesterol abundance assisted the internalization and degradation of ErbB2. The cholesterol-lowering drug lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. Conclusion The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.

Two new thymol derivatives (compounds 1–2) were isolated from the roots of Eupatorium chinense. Their structures were elucidated by analysis of MS data and extensive 1D and 2D NMR spectroscopy (1H-1H COSY, HMBC, HSQC and NOESY). The absolute configuration of compound 1 was assigned based on a comparison of calculated and experimental ECD. Compounds 1–2 were tested in vitro for their cytotoxic activities against three cancer cell lines CNE 2, Caski and HGC-27. Among them, compound 1 showed notable cytotoxic activities against the three cancer cell lines with IC50 values ranging from 4.2 to 11.9 μM.

The chemical modification of the primary amino groups of amino acid derivatives and peptides is an important process in the pharmaceutical industry and the field of chemical biology. However, suitable reactions that can be carried out under mild and environmentally friendly conditions are limited. We present a versatile method to selectively modify primary amino groups using novel dihydrooxazolo[3,2-a]quinoliniums in 1-butanol as solvent under mild and metal-free conditions. The application of this method to peptides with primary amino, secondary amino, amide, alcoholic hydroxyl, phenolic hydroxyl, disulfide bond, ester and cyano groups revealed that only the primary amino groups were selectively modified, suggesting that this method is compatible with other reactive moieties. We also demonstrated that the quinolylation of existing peptides affected peptide bioactivity and stability, indicating that the novel dihydrooxazolo[3,2-a]quinoliniums can be widely applied, especially in medicinal chemistry and chemical biology.

The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20 mg/kg, orally) and ARA (10, 20 and 40 mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10 mL/kg) containing 15 mg/mL aspirin 4 h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.

Four new α-pyrone derivatives, xylariaopyrones A-D (1-4), together with four known compounds were isolated from the PDB broth of endophytic fungus xylariales sp. (HM-1). Their structures were identified by comprehensive analysis of NMR, MS and CD spectra. The absolute configurations of compounds B-D were determined by calculating their ECD spectra. Compound C (3) and D (4) was a pair of epimer with a ketal function group. The eight obtained metabolites were evaluated to four cancer cell lines, but they showed no significative data with IC50 > 50 μg/mL. And the antimicrobial assay results appeared that xylariaopyrones A-D displayed the inhibiting activity with MIC value ranging from 20.5 to 50.6 μg/mL. Finally, the results of brine shrimp inhibiting activity from eight compounds displayed different inhibiting ratio from 40% to 92%.

Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO3 or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC50 values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death.

The huge economic loss of citrus fruit after harvest called for safe and efficient preservatives, as chemically synthesized agents threatened the environment and human health. Herein a biocontrol fungus Chaetomium globosum QY-1 near the orchard in riparian area was identified to have antimicrobial, antioxidant and tyrosinase inhibition activity, which meets the requirements of an ideal preservative. Metabolite profiling based on bioassay-guided fractionation was carried out, and eight polyketones were determined by MS and NMR. The most abundant CheA exhibited strong inhibition to Penicillium digitatum, the main pathogen caused citrus fruit rot. Among these metabolites, Epicoccone and Epicoccolide B showed higher antioxidant activity, while Epicoccone and CheA had higher tyrosinase inhibitory activity. All the activities were close to or even better than the positive control (Vc; glutathione; Vc and arbutin; Bellkute), implying that the metabolites of C. globosum had comprehensive effects as natural preservatives.

The atomic-scale steps are ubiquitous on graphene. The frictional behavior of graphene at atomic-scale steps under different relative humidity (RH) is very important for application of graphene as solid lubricant in complicated environment. Frictional properties at atomic-scale graphene steps were investigated using calibrated atomic force microscopy (AFM) in various RH. Lateral force at uncovered atomic step decreased with the increase of RH, while lateral force at covered step were independent of RH. Uncovered steps possessed higher work function than graphene plane from the scanning Kelvin probe microscopy (SKPM) measurement due to the existence of dangling bonds and oxygen-containing functional groups. Then the adsorption of water molecule on hydrophilic oxygen containing functional groups at uncovered step decreased the work function and reduced the lateral force under high RH. Also, lateral force at steps increased even fast than plane after plasma treatment, because dangling bonds is easier to be oxide functionalization. The studies provide a further understanding of frictional properties at atomic scale steps and could be helpful in the applications of graphene as solid lubricant in humid environment.

Interfacial friction is of crucial importance to ensure the friction-reducing and anti-wear properties of mechanical microstructures in micro/nanoelectromechanical systems (MEMS/NEMS). An ultra-low frictional interface combining hydrophobic 1H,1H,2H,2H-perfluorodecyltrichlorosilane (FDTS) self-assembled monolayers (SAMs) coated on an AFM tip with mechanically exfoliated molybdenum disulfide (MoS2) nanosheets deposited on a planar Si/SiO2 substrate was achieved. The FDTS SAMs/MoS2 interface between the FDTS SAMs and the MoS2 nanosheets exhibits an ultra-low friction force that is independent of the relative humidity. The incommensurate contact with ultra-low energy dissipation between FDTS and MoS2 nanosheets and hydrophobic surface properties lead to this ultra-low frictional FDTS SAMs/MoS2 interface. Also, the MoS2 nanosheets have a high elastic modulus, which gives them a smaller contact area than the FDTS SAMs and contributes to the low friction. The excellent hydrophobic properties of both the FDTS SAMs and MoS2 enable them to be unaffected by the relative humidity by preventing the capillary interaction. This study paves the way for extensive applications in reducing the friction of nanoscale contact interfaces.

Membrane fouling has been a major challenge in the practical application of membrane technology for wastewater treatment and purification. In this study, a reusable membrane composed of g-C3N4@TiO2-nanowires modified graphene oxide (GO/CN@TNWs) was successfully fabricated through electrostatic interactions and a vacuum filtration-assisted self-assembly process. The as-fabricated membrane possessed higher photocatalytic activity than the pure TNWs under simulated solar light exposure, attributing to the introduction of GO with high absorption and carrier mobility, and the synergistic effects of TNWs and CN. Furthermore, the π-π stacking interactions between GO and organic pollutant molecules contribute to the excellent enrichment efficiency of GO/CN@TNWs membrane (98.77%) toward tetracycline hydrochloride (TCH). Room-temperature ESR studies indicate that the GO/CN@TNWs membrane can generate more superoxide radical, hydroxyl radical and hole species for photocatalytic degradation. Therefore, the GO/CN@TNWs membrane may be used for TCH removal from waste water and the excellent solar-light-driven photocatalytic performance endows GO/CN@TNWs membrane absorbents with recycling abilities for the realization of large-scale wastewater purification.

PA forms a biofilm resistant to antibiotics, hindering antibiotics efficacy and preventing the eradication of PA, has attracted much attention for its biofilm. In this study, we first established and validated an efficient and sensitive gas chromatography-mass spectrometry (GC–MS) method for the quantification of metabolites in biofilm. Decanoic acid was used as the internal standard. The separation of Palmitic acid, stearic acid and Decanoic acid was conducted on an Elite-5 MS column (30 m × 0.25 mm, 0.25 μm) using gradient elution condition at a flow rate of 1 mL/min. Palmitic acid, stearic acid and Decanoic acid were determined under the positive ionization mode, respectively. The calibration curve of Palmitic acid and stearic acid were established in the range of 4 to 128 μg/mL (r2 = 0.999). The recovery of palmitic acid and stearic acid were between 98.76% and 113.91%, RSD ＜ 5%. The well validated method was used to detect the metabolites of Pseudomonas aeruginosa biofilm. 54 metabolites were isolated and identified from biofilm samples, and 7 important signal pathways were identified by KEGG enrichment analysis. ABC transporters and bacterial chemotaxis signaling pathways have an important impact on the growth of PA biofilm among these metabolic pathways. This study provides valuable references for the further study of PA biofilm, especially the change of metabolite content and the search for biomarkers.

A solid-state reaction process with poly(vinyl alcohol) as the carbon source is developed to synthesize LiFePO4-based active powders with or without modification assistance of a small amount of Li3V2(PO4)3. The samples are analyzed by X-ray diffraction, scanning/transmission electron microscopy, and Raman spectroscopy. It is found that, in addition to the minor effect of a lattice doping in LiFePO4 by substituting a tiny fraction of Fe2+ ions with V3+ ions, the change in the form of carbon coating on the surface of LiFePO4 plays a more important role to improve the electrochemical properties. The carbon changes partially from sp3 to sp2 hybridization and thus causes the significant rise in electronic conductivity in the Li3V2(PO4)3-modified LiFePO4 samples. Compared with the carbon-coated baseline LiFePO4, the composite material 0.9LiFePO4·0.1Li3V2(PO4)3 shows totally different carbon morphology and much better electrochemical properties. It delivers specific capacities of 143.6 mAh g−1 at 10 C rate and 119.2 mAh g−1 at 20 C rate, respectively. Even at the low temperature of −20 °C, it delivers a specific capacity of 118.4 mAh g−1 at 0.2 C.

Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene. Moreover, β-elemene regulated the polarization of macrophages from M2 to M1. β-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate β-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy.

An inexpensive and effective cobalt coordinated conjugated microporous polymer (Co-CMP-2) made up from cross-linked an ethanediamine-based salen ligand with 1,3,5-triethynylbenzene. Co-CMP-2 exhibited extremely high catalytic efficiency in the synthesis of cyclic carbonates from CO2 and epoxides, which is superior to that of previously reported Co-CMP. Co-CMP-2 achieved a TOF of 23300 h−1 for ethylene carbonate. Moreover, the catalyst can be reused more than 10 times without significant loss in activity.

Excessive activation of macrophages has been implicated in various types of inflammatory injury. Suppression of macrophage activation would have therapeutic benefits, leading to the alleviation of the progression of inflammatory diseases. Eburicoic acid (EA) is one of main bioactive components isolated from Laetiporus sulphureus (Bull.:Fr.) Murrill. In our previous study, we found that EA possessed anti-inflammatory activities. However, the cellular and molecular mechanisms underlying its anti-inflammatory activities remain to be poorly understood. The present study aimed to further evaluate its effect on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophage cells. We investigated the anti-inflammatory effect by modulating LPS-induced activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/nuclear transcription factor-κB (NF-κB) pathway in RAW264.7 cells. The results showed that EA caused no obvious cytotoxicity, and its suitable concentrations on RAW264.7 cells were in the range from 0.02 to 0.08 μM. EA significantly inhibited the releases of inflammatory mediators, nitrite oxide (NO) and prostaglandin E2 (PGE2); suppressed mRNA and protein expression levels of inducible nitrite oxide synthase (iNOS) and cyclooxygenase-2 COX-2 and pro-inflammatory cytokine TNF-α, IL-6, and IL-1β; and reduced levels of phosphorylated PI3K, Akt, mTOR, and NF-κBp65 in LPS-induced RAW264.7 cells in dose- and time-dependent manners. These aforementioned results indicated that EA executed anti-inflammatory effect on LPS-induced RAW264.7 cells, and this effect might be achieved via suppressing the PI3K/Akt/mTOR/NF-κB signaling pathway and inhibiting the LPS-induced productions of inflammatory mediators and pro-inflammatory cytokines.

Peniopyranone ( 1 ) and 2-methoxyl- β - l -Arabinofuroside uracil ( 2 ), together with six known compounds were isolated from the broth of Penicillium sp. (NO. 64). And their structures were established by comprehensive analysis of NMR, MS and CD spectra, the absolute configurations of Peniopyranone ( 1 ) were determined as 7 S , 8 S and 9 R by calculating its ECD. The eight obtained metabolites were subjected to evaluate the preliminary cytotoxic activities to four cancer cell lines, but they showed no significant data with IC 50 > 50 μmol/mL. The results of acetylcholinesterase inhibiting assay showed that peniopyranone ( 1 ) displayed the inhibition activity to acetylcholinesterase with IC 50 at 15.2 μmol/mL.

Three new terpenoids compounds ( 1–3 ) were obtained from ethyl acetate fraction, which was yielded from Eupatorium chinense ’ s ethanol extract . Their structures were determined on the basis of 1D and 2D NMR spectroscopy, including 1 H- 1 H COSY, HMBC, HSQC and NOESY experiments. All of the isolated compounds were tested in vitro for their cytotoxic activities against the HepG 2 , HGC-27 and MDA-MB-231 cancer cell lines.

A complete and ordered layered structure on the surface of LiNi0.815Co0.15Al0.035O2 (NCA) has been achieved via a facile surface-oxidation method with Na2S2O8. The field-emission transmission electron microscopy images clearly show that preoxidation of the hydroxide precursor can eliminate the crystal defects and convert Ni(OH)2 into layered β-NiOOH, which leads to a highly ordered crystalline NCA, with its (006) planes perpendicular to the surface in the sintering process. X-ray photoelectron spectroscopy and Raman shift results demonstrate that the contents of Ni2+ and Co2+ ions are reduced with preoxidization on the surface of the hydroxide precursor. The level of Li+/Ni2+ disordering in the modified NCA determined by the peak intensity ratio I(003)/I(104) in X-ray diffraction patterns decreases. Thanks to the complete and ordered layered structure on the surface of secondary particles, lithium ions can easily intercalate/extract in the discharging–charging process, leading to greatly improved electroc...

It has been widely recognized that inflammation, particularly chronic inflammation, can increase the risk of cancer and that the simultaneous treatment of inflammation and cancer may produce excellent therapeutic effects. Berberine, an alkaloid isolated from Rhizoma coptidis, has broad applications, particularly as an antibacterial agent in the clinic with a long history. Over the past decade, many reports have demonstrated that this natural product and its derivatives have high activity against both cancer and inflammation. In this review, we summarize the advances in studing berberine and its derivatives as anti-inflammatory and anti-tumor agents in the digestive system; we also discuss their structure-activity relationship. These data should be useful for the development of this natural product as novel anticancer drugs with anti-inflammation activity.

Chromium (Cr)-based coatings have been widely used to strengthen the friction reduction and wear resistance on various kinds of surface. Here, the stable aqueous dispersion of oxidized multi-walled carbon nanotube (MWCNT) and graphene oxide nanosheets (GOS) was obtained by ultrasonic oxidation treatment. Then, MWCNT-Cr and GOS-Cr composite coatings were prepared using the direct current electrochemical co-deposition process on 420 stainless steel in the electrolyte with the addition of MWCNT and GOS under different current density and temperature. The morphology, structure, hardness and tribological properties of MWCNT-Cr and GOS-Cr composite coating are comparatively studied using pure Cr coating as a baseline. The friction reduction performance of MWCNT-Cr and GOS-Cr composite coatings was improved at optimum current density and temperature. The anti-wear properties of MWCNT-Cr and GOS-Cr composite coatings were enhanced by uniform embedment of MWCNT and GOS in coatings increasing the hardness and lubricity. This study suggests that the introduction of oxidized MWCNT and GOS with good dispersion could enhance the wear resistance and friction reduction of pure Cr coating due to their excellent dispersion, mechanical, and lubricant properties.

This paper reports the tandem reaction strategy of the Passerini/Staudinger/aza-Wittig reaction based on the in situ capture of isocyanides. According to this strategy, isocyanides are synthesized in situ and immediately work as the substrate for the Passerini reaction and postmodification tandem reaction in one pot. In addition, two types of new compounds, 5-oxo-3,5-dihydrobenzo[ e][1,4]oxazepines and 6-oxo-5,6-dihydro-2 H-1,4-oxazines, were synthesized using the tandem reaction strategy that includes five-step transformations in one pot.

Ten new ambuic acid derivatives, pestallic acids H–Q including one new iodinated natural product along with two known compounds, ambuic acid and ambuic acid 18-acetate, were obtained through fermentation of the endophytic fungus Pestalotiopsis lespedezae on solid rice medium with 3.5% NaI. Pestallic acids H–Q were undetectable in cultures of the fungus grown on solid rice medium lacking NaI or in those where NaI had been replaced by NaCl or NaBr. The structures of the new metabolites were established on basis of 1D/2D NMR and HRESIMS data. Their absolute configurations were determined by Mosher’s method and TDDFT-ECD calculations. The compounds failed to show antibacterial activity against S. aureus (ATCC29213), drug-resistant Acinetobacter baumannii (BAA1605) or Mycobacterium tuberculosis, as well as cytotoxicity against the mouse lymphoma cell line L5178Y.

7-epi-Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7-hydroxyl group simply using Ag2O as catalyst and DMF as solvent. The catalyst could be quantitatively recovered by filtration without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives (e.g., docetaxel and paclitaxel) to 7-epi-taxane derivatives (e.g., 7-epi-docetaxel and 7-epi-paclitaxel). Furthermore, 33 ester derivatives of 7-epi-taxane with different amino acid moieties at the position of C-13 were successfully synthesized via esterification without protecting C-7-OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with IC50 value as low as 15.9 nmol/L for 18.

Asymmetric synthesis of 3,4-dihydro-2 H -1,2,4-benzothiadiazine-1,1-dioxides (DHBDs) was realized using readily available scandium(III)- inda -Pybox as the catalyst. It represents the first example focusing on systematic study of asymmetric synthesis of DHBDs, and a series of enantioselective 3-alkyl, or 3-aryl DHBDs were obtained with up to 93% ee.

A concise approach for the synthesis of 2-substituted quinazolinones using an iron-catalyzed tandem reaction of 2-aminobenzamides with acyclic or cyclic 1,3-diketones via condensation, intramolecular nucleophilic addition, C–C bond cleavage in an aqueous solution of poly(ethylene glycol) under oxidant-free conditions has been developed.

Graphene is a two-dimensional nanomaterial with high specific surface area, excellent physical and chemical properties with great potential in sensor applications. Uniform nanocrystalline Pt–Pd nanoparticle-decorated reduced graphene oxide (Pt–Pd/RGO) has been synthesized via a one-step chemical reduction. Dielectrophoresis applied to Pt–Pd/RGO fabricated the sensor. The hydrogen sensing properties of Pt–Pd/RGO were studied by recording the resistance changes following exposure to hydrogen at different concentrations, temperatures, flow rate and with different carrier gases. The Pt–Pd/RGO sensor has a stable and repeatable response due to carrier donation and crystal lattice expansion over hydrogenation and dehydrogenation. The maximum response tends to increase with the increase of hydrogen concentration or decrease of operating temperature, but remained almost unaffected by the flow rate. The nitrogen as carrier gas possesses higher response and longer recovery time than air because oxygen participates in the reaction. These studies have potential for the development of novel H2 sensors.

Nano-spherical Li-rich cathodes and MnxCo1−xO anodes are synthesized from as-solvothermal MnxCo1−xCO3 (x = 1, 0.8, and 0.5) precursors. Based on the half-cell studies of these materials, Li-rich 0.5Li2MnO3·0.5LiMn0.5Ni0.5O2 with a high reversible capacity of 247 mA h g−1 and binary transition metal oxide Mn0.8Co0.2O with a reversible capacity of 759 mA h g−1 are selected respectively as the optimal positive and negative electrodes to construct a full cell. Such an electrode match-up, i.e. Li-rich/Mn0.8Co0.2O full cell (“N-cell”), allows no need for pre-activation of the metal oxide anode. This “N-cell” can deliver a high reversible capacity of 205 mA h g−1 and particularly rather high volumetric energy density, which is about 31% higher than that of a Li-rich/graphite full cell (“T-cell”). The special coulombic efficiency match-up and tailored microstructures and compositions of the electrode materials are all crucial to achieve such a high energy density.

Graphene-decorated Na3V2(PO4)3 (NVP@G) material is synthesized through an in situ catalytic process using the intermediate product component VOx as a catalyst and polyvinyl alcohol as the graphene source. NVP@G shows a superb rate performance and an ultralong cycle life.

Three new sesquiterpenoids (1–3) and four new benzofuran dimers (+)-4 and (−)-4, (+)-5 and (−)-5, and four known benzofuran dimers (+)-6 and (−)-6, (+)-7 and (−)-7 were isolated from the underground parts of Eupatorium chinense. The enantiomers of racemates (±)-4 ~ (±)-7 were separated by chiral HPLC columns, and their absolute configurations were determined by circular dichroism experiments. The structures of all new compounds were elucidated on the basis of their NMR, and MS data as well as by comparison with literature values. The all of the isolated compounds were tested in vitro for their cytotoxic activities against the Caski, MDA-MB-231 and HepG2 cancer cell lines.

Homocysteine-inducible endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible membrane protein involved in ER-associated degradation. Herp expression is maintained at low levels through a strict regulatory mechanism, but the details of this mechanism and the reasons why Herp expression is restricted in this manner remain unclear. Here, we show that Herp degradation involves synoviolin, an ER-resident E3 ubiquitin ligase. Herp protein levels were found to be markedly elevated in synoviolin-null cells, and Herp expression decreased when synoviolin was overexpressed. However, the lysine residues of Herp, which are ubiquitinated by E3 ubiquitin ligase, were not sufficient for regulation of Herp degradation. These results suggest that Herp degradation is mediated via synoviolin and that Herp ubiquitination involves amino acids other than lysine.

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their NMR (Nuclear Magnetic Resonance), MS (Mass Spectrum) and CD (Circular Dichroism) spectra. Aspergoterpenin A (1) was the first example with a characteristic ketal bridged-ring part in the degraded natural bisabolane-type sesquiterpene structures. The compounds 1–12 displayed no significant activities against four cancer cell lines (A549, Caski, HepG2 and MCF-7). Further, the antimicrobial activities to Erwinia carotovora sub sp. Carotovora were evaluated, and the results showed that compounds 1–12 displayed antimicrobial activities with MIC values ranging from 15.2 to 85.2 μg/mL.

Graphene and functionalized graphene are promising candidates as ultrathin solid lubricants for dealing with the adhesion and friction in micro- and nanoelectromechanical systems (MEMS and NEMS). Here, the dynamic friction and adhesion characteristics of pristine graphene (PG), graphene oxide (GO), and fluorinated graphene (FG) were comparatively studied using atomic force microscopy (AFM). The friction as a function of load shows nonlinear characteristic on GO with strong adhesion and linear characteristic on PG and FG with relatively weak adhesions. An adhesion enhancement phenomenon that the slide-off force after dynamic friction sliding is larger than the pull-off force is observed. The degree of adhesion enhancement increases with the increasing surface energy, accompanied by a corresponding increase in transient friction strengthening effect. The dynamic adhesion and friction enhancements are attributed to the coupling of dynamic tip sliding and surface hydrophilic properties. The atomic-scale stick-slip behaviors confirm that the interfacial interaction is enhanced during dynamic sliding, and the enhancing degree depends on the surface hydrophilic properties. These findings demonstrate the adhesive strength between the contact surfaces can be enhanced in the dynamic friction process, which needs careful attention in the interface design of MEMS and NEMS.

Five new guaiane-type sesquiterpene lactones, caroguaianolide A–E (1–5), along with nine known sesquiterpene lactones (6–14) were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic date, HRESIMS analysis, and comparison of experimental and calculated ECD data. All isolated compounds (1–14) were tested in vitro for their cytotoxic activities against the MDA-MB-231, HGC-27 cancer cell lines, of which compounds 1–3, 6, 7, 11 and 12 showed significant cytotoxic activities with IC50 values ranging from 2.67 to 12.34 μM.

A novel gold-catalyzed C-glycosylation has been developed to gain access to α,(Z)-selective C-vinyl glycosides, starting from readily available glycals and propargylic carboxylate. This reaction involves a tandem intermolecular gold-catalyzed 1,3-acyloxy migration/Ferrier rearrangement with the involvement of allenic ester as the glycosyl acceptor. A wide range of substrate scope with good to excellent yields was achieved with complete diastereoselectivity. Ministry of Education (MOE) National Research Foundation (NRF) Accepted version We thank the Ministry of Education (MOE 2013-T3-1-002), National Research Foundation (NRF2016NRF-NSFC002-005), Nanyang Technological University, Singapore (RG14/16), China Scholarship Council (No. 201508420062), and Youth Talent Development Foundation of China Three Gorges University for their financial support. Dr. Yongxin Li and Dr. Ganguly Rakesh in the division of chemistry and biological chemistry, Nanyang Technological University are also acknowl-edged for X-ray analysis.

A high-efficient and stereo-specific approach for the preparation of biologically important (E)-2-styryl-tetrahydrobenzo[d]thiazoles has been developed via TMSCl promoted direct sp3 C-H alkenylation of 2-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one under metal-free conditions. Seventeen target compounds were synthesized in excellent yields of 82% –98% under the optimal conditions of 300 mol% TMSCl at 110°C for 2 h, and their chemical structures were elucidated by IR, NMR, ESI-MS, elemental analyses and X-ray crystallography analysis. A plausible mechanism was also proposed, and this method provided a good functional group conversion for the sp3 C-H substrates.