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A new type of explosive ink formulation that can be quickly cured was prepared with unsaturated polyester as binder, styrene as active monomer, 2,4,6-trimethylbenzoyl-diphenylphosphine oxide as photoinitiator, and hexanitrohexaazaisowurtzitane (CL-20) as the main explosive. Then the explosive ink direct writing technology was used to charge the micro-sized energetic devices, the curing mechanism of the explosive ink was discussed, and the microstructure, safety performance and explosive transfer performance of the explosive ink molded samples were tested and analyzed. Results indicate that the composite material has a fast curing molding speed, its hardness can reach 2H within 8 min. The crystal form of CL-20 in the molded sample is still e type. The CL-20 based UV-curing explosive ink formulation has good compatibility, its apparent activation energy is increased by about 3.5 kJ/mol. The composite presents a significant reduction in impact sensitivity and its characteristic drop height can reach 39.8 cm, which is about 3 times higher than the raw material. When the line width of charge is 1.0 mm, the critical thickness of the explosion can reach 0.015 mm, and the explosion velocity is 7129 m/s when the charge density is 1.612 g/cm3.

The zinc uptake regulator (Zur) is a member of the Fur (ferric uptake regulator) family transcriptional regulators that plays important roles in zinc homeostasis and virulence of bacteria. Upon zinc perception, Zur binds to the promoters of zinc responsive genes and controls their transcription. However, the mechanism underlying zinc-mediated Zur activation remains unclear. Here we report a 2.2-Å crystal structure of apo Zur from the phytopathogen Xanthomonas campestris pv. campestris (XcZur), which reveals the molecular mechanism that XcZur exists in a closed inactive state before regulatory zinc binding. Subsequently, we present a 1.9-Å crystal structure of holo XcZur, which, by contrast, adopts an open state that has enough capacity to bind DNA. Structural comparison and hydrogen deuterium exchange mass spectrometry (HDX-MS) analyses uncover that binding of a zinc atom in the regulatory site, formed by the hinge region, the dimerization domain and the DNA binding domain, drives a closed-to-open conformational change that is essential for XcZur activation. Moreover, key residues responsible for DNA recognition are identified by site-directed mutagenesis. This work provides important insights into zinc-induced XcZur activation and valuable discussions on the mechanism of DNA recognition., Graphical Abstract Graphical AbstractA proposed model of zinc-perception-induced DNA binding for XcZur. In the model, apo XcZur is in a closed inactive state. Zinc perception in the regulatory zinc binding site induces a 180° rotation of the hinge region to drive a closed-to-open conformational change of the XcZur dimer. Holo XcZur thus bears an active state, in which the putative DNA binding elements, especially the recognition helix (H4), are precisely positioned and poised for DNA binding. Subsequently, holo XcZur binds with DNA in a mechanism of mutual induced fit and regulates DNA transcription.

Hydroxyapatite (HAp) nanoparticles stabilized Pickering emulsions were prepared by dichloromethane (CH2 Cl2 ) dissolved poly(L-lactic acid) (PLLA) as the oil phase and the deionized water with different concentrations of cetyltrimethyl-ammonium bromide (CTAB) as the aqueous phase. Effect of CTAB concentration on emulsions type and stability were studied. The emulsion type underwent a two-phase inversion, and emulsion stability increased first and then decreased with increasing CTAB concentrations. Besides, effect of CTAB concentration on zeta potential, aggregate size, contact angle of HAp nanoparticles and the oil-water interfacial tension were studied. The results indicated that zeta potential value of HAp nanoparticles changed from negative to positive, and the contact angle increased to over 80° initially and then decreased to below 40° rapidly. The distribution of HAp nanoparticles on the surface of emulsion droplets with different concentrations of CTAB (5 and 20 mM) was characterized using laser-induced confocal microscope. It revealed the distribution of HAp nanoparticles changed with different CTAB concentrations. The cured PLLA materials were obtained after the solvent being volatilized using as-received emulsions as templates. Scanning electron microscope images showed both microspheres and porous materials with interconnected pore structure were obtained. In conclusion, the microstructure of microspheres or porous PLLA materials is controllable by adjusting the property of HAp nanoparticles stabilized Pickering emulsions with appropriate amount of CTAB.

The effect of lead on the catalytic performance of Mn-Ce/TiO2 catalysts in the selective catalytic reduction (SCR) of NOx with ammonia at low temperature was investigated; with the help of nitrogen sorption, XRD, FT-IR spectroscopy, H2-TPR and NH3-TPD characterization, the causes of lead poisoning and acid regeneration were clarified. The results indicate that the doping of Pb in Mn-Ce/TiO2 leads to a significant decrease of the low-temperature SCR activity; with a Pb loading of 11%, the conversion of NO over Mn-Ce/TiO2 at 180°C decreases from original 100% on the fresh catalyst to 44% on the Pd-poisoned catalyst. The presence of Pb may reduce the content of active Mn4+ and Ce3+ species on the Mn-Ce/TiO2 catalyst, which suppresses the redox cycle of Mn4+ + Ce3+ ↔ Mn3+ + Ce4+; moreover, the decrease of surface acidity on the Mn-Ce/TiO2 catalyst by the doping of Pb is also disadvantageous to the adsorption and activation of NH3. The Pd-poisoned Mn-Ce/TiO2 can be regenerated by nitric acid treatment; after the regeneration, the catalytic activity of Mn-Ce/TiO2 in NH3-SCR of NO is almost completely recovered and even exceeds that of the fresh catalyst at 80–150°C. The nitric acid treatment can restore the redox capacity of Mn-Ce/TiO2, increase the surface area, and create new acid sites, which contribute to recovery of the activity of Pb-poisoned Mn-Ce/TiO2 catalyst in NH3-SCR.

BACKGROUND Bone marrow mesenchymal stem cells (BMSCs) are capable of shifting the microglia/macrophages phenotype from M1 to M2, contributing to BMSCs-induced brain repair. However, the regulatory mechanism of BMSCs on microglia/macrophages after ischemic stroke is unclear. Recent evidence suggests that mesencephalic astrocyte–derived neurotrophic factor (MANF) and platelet-derived growth factor-AA (PDGF-AA)/MANF signaling regulate M1/M2 macrophage polarization. AIM To investigate whether and how MANF or PDGF-AA/MANF signaling influences BMSCs-mediated M2 polarization. METHODS We identified the secretion of MANF by BMSCs and developed transgenic BMSCs using a targeting small interfering RNA for knockdown of MANF expression. Using a rat middle cerebral artery occlusion (MCAO) model transplanted by BMSCs and BMSCs–microglia Transwell coculture system, the effect of BMSCs-induced downregulation of MANF expression on the phenotype of microglia/macrophages was tested by Western blot, quantitative reverse transcription-polymerase chain reaction, and immunofluorescence. Additionally, microglia were transfected with mimics of miR-30a*, which influenced expression of X-box binding protein (XBP) 1, a key transcription factor that synergized with activating transcription factor 6 (ATF6) to govern MANF expression. We examined the levels of miR-30a*, ATF6, XBP1, and MANF after PDGF-AA treatment in the activated microglia. RESULTS Inhibition of MANF attenuated BMSCs-induced functional recovery and decreased M2 marker production, but increased M1 marker expression in vivo or in vitro. Furthermore, PDGF-AA treatment decreased miR-30a* expression, had no influence on the levels of ATF6, but enhanced expression of both XBP1 and MANF. CONCLUSION BMSCs-mediated MANF paracrine signaling, in particular the PDGF-AA/miR-30a*/XBP1/MANF pathway, synergistically mediates BMSCs-induced M2 polarization.

Background and purpose Non-alcoholic fatty liver disease (NAFLD) is a worldwide public health problem with no established pharmacological therapy. Here, we explored the potential benefit of P7C3-A20, a novel aminopropyl carbazole compound with neuroprotective activity, in a NAFLD model, induced in mice by a high-fat diet (HFD). Experimental approach C57BL/6J mice were given a HFD (42% fat content) for 16 weeks to induce NAFLD. P7C3-A20 (20 mg·kg-1 ·day-1 ) was given by gavage for 2 weeks. Indirect calorimetry, histological analysis, immunoblotting, immunohistochemistry, and biomedical examinations were performed. Gut microbiota were determined using a 16S ribosomal RNA sequencing analysis. Key results P7C3-A20 treatment reduced body weight gain/adiposity, improved insulin resistance, promoted energy expenditure (O2 consumption/CO2 production), inhibited lipid oxidation, suppressed hepatic inflammation (Kupffer cell number and pro-inflammatory factors), decreased necroptosis/apoptosis (receptor-interacting protein kinase 3, cleaved caspase-3, and TUNEL), and alleviated liver fibrosis and injury. Mechanistically, P7C3-A20 stimulated FGF21 and FGF1 via activating liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK), which further resulted in a reduced nuclear translocation of CREB-regulated transcription coactivator 2 (CRTC2). In AMPKα2 knockout mice, the protection of P7C3-A20 against HFD-induced metabolism abnormalities and fat accumulation, as well as the elevation of blood FGF21 and FGF1, was abolished. P7C3-A20 increased the gut microbiota species richness. Moreover, it enhanced the proportions of Akkermansia, Lactobacillus, and Prevotellaceae, while reducing the proportions of Enterobacteriaceae, Escherichia, and Parasutterella. Conclusions and implications P7C3-A20 increased levels of NAD+ and alleviated NAFLD through stimulating FGF21 and FGF1 in an LKB1/AMPK/CRTC2-dependent manner and shaping gut microbiota. Linked articles This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.

It is always challenging to fabricate two-dimensional transition-metal dichalcogenides into multiple hollow micro-/nanostructures with improved properties for various potential applications. Here, hierarchically porous MoS2-C hollow rhomboids (MCHRs) have been creatively synthesized via a facile self-templated solvothermal approach. It has been clarified that the obtained MCHRs assembled beneath ultrathin γ-MnS and carbon cohybridized MoS2 nanosheets under the structural direction of the MnMoO4·0.49H2O self-template. The prepared MCHR anode of sodium-ion batteries exhibited a reversible capacity of 506 mA h g-1 at 0.1 A g-1, ultrahigh rate capabilities up to 10 A g-1 with 310 mA h g-1, and exceptional stability over 3000 cycles. This study provides inspiration for the rational design of hierarchically porous hollow nanostructures with specific geometries as an excellent electrode material for outstanding performance energy storage equipment.

The design of high efficiency, low-cost, and long-durability bifunctional electrocatalysts for the oxygen reduction/evolution reactions (ORR/OER) is crucial to some critical energy conversion and storage systems including fuel cells and water splitting. Herein, we developed a facile strategy to fabricate a CoNx/NiFeOx/nitrogen-doped reduced graphene oxide (N-RGO) nanocomposite derived from ternary CoNiFe-layered double hydroxides (LDHs)/polypyrrole (PPy)/RGO precursor for both ORR and OER. Based on the synergistic effect among different components, the resulting CoNx/NiFeOx/N-RGO nanocomposite exhibits not only superior ORR activities (a half-wave potential (E1/2) of 0.78 V vs. RHE and a J1600 rpm of − 4.80 mA cm−2 at 0.5 V vs. RHE) but also moderate OER activities (an overpotential η10 mA cm−2 of 372 mV) in alkaline media. The overall oxygen electrode performance of CoNx/NiFeOx/N-RGO demonstrates the smallest ΔE (EOER, 10 mA cm−2-EORR, − 3 mA cm−2) value of 0.82 V compared with the benchmark (commercial 20 wt% Pt/C and RuO2/C). Furthermore, CoNx/NiFeOx/N-RGO shows good durability in ORR and OER, making it promising applications for oxygen electrocatalysis.

High metastatic propensity is a devastating challenge to effective therapy of solid tumors, including triple-negative breast cancer (TNBC). In this study, we performed a genome-scale screen and found that cholesterol homeostasis is essential for tumor progression in immunocompetent mice. In an orthotopic TNBC model, intracellular cholesterol promoted lung metastasis by sustaining the expression of keratin 14 (KRT14) and decreasing MHC II, which was indispensable for the cluster metastasis of TNBC. Mechanistic studies demonstrated that FOXO3a regulated the transcription of KRT14. FOXO3a recognized and directly bound to the promoter of KRT14 to inhibit its expression. Cholesterol disrupted the nuclear translocation of FOXO3a by sustaining its phosphorylation, which was regulated by IKK, one of the major upstream kinases of FOXO3a. Apolipoprotein A1 (ApoA1) increased cholesterol efflux and inhibited TNBC metastasis by regulating the IKK-FOXO3a-KRT14 axis. The recombinant adenovirus encoding ApoA1 (ADV-ApoA1) promoted cholesterol efflux, dampened metastasis, and prolonged survival in mice bearing TNBC. Finally, we provided preliminary data showing that high doses of ADV-ApoA1 were well tolerated in rhesus monkeys and Syrian hamsters injected both intravenously and hypodermically. Taken together, cholesterol promotes metastasis via the IKK-FOXO3a-KRT14 axis in TNBC, and facilitating cholesterol efflux from TNBC cells is a promising therapeutic strategy for TNBC clinical treatment.

Optical quantum network plays an important role in large scale quantum communication. However, different components for photon generation, transmission, storage and manipulation in network usually cannot interact directly due to the wavelength and bandwidth differences, and thus interfaces are needed to overcome such problems. We propose an optical interface for frequency down-conversion and bandwidth compression based on the counter-propagating quasi-phase-matching difference frequency generation process in the periodically-poled lithium niobate on insulator waveguide. We prove that a separable spectral transfer function can be obtained only by choosing proper pump bandwidth, thus relaxing the limitation of material, dispersion, and working wavelength as a result of the counter-propagation phase-matching configuration. With numerical simulations, we show that our design results in a nearly separable transfer function with the Schmidt number very close to 1. With proper pump bandwidth, an photon at central wavelength of 550 nm with a bandwidth ranging from 50 GHz to 5 THz can be converted to a photon at central wavelength of 1,545 nm with a much narrower bandwidth of 33 GHz.

Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (Aβ) generation in the brain. However, the potential effect of lead exposure on Aβ transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The Aβ clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-α and IL-1β in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aβ transportation, were disturbed by developmental lead exposure. All these pathologies resulted in Aβ1-40 deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for Aβ endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces Aβ deposition in BCSFB and BBB and impairs Aβ clearance in the liver, which would ultimately disturb Aβ transportation via choroid plexus/brain microvessels and facilitate Aβ deposition in the brain.

Six undescribed protoberberine derivatives including two pairs of enantiomers, named yanhusanines G-L, along with fifteen reported protoberberine alkaloids, were isolated from the tubers of Corydalis yanhusuo. Among them, yanhusanines H-L feature a unique 13,13a-seco skeleton which is rare in nature. Their structural elucidations were achieved by extensive spectroscopic analysis and quantum chemistry calculations. A biogenetic route for yanhusanines H-L was proposed. Bioassay results showed that yanhusanine J exhibited potent inhibitory effect against the nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 cells (IC50 = 2.25 ± 1.32 μM). Western blot analysis demonstrated that yanhusanine J exerted its anti-inflammatory effect via suppressing the nuclear factor kappa B (NF-κB) pathway, together with the decrease of the inflammatory factors TNF-α, IL-6 and IL-1β. Furthermore, molecular simulation docking indicated that yanhusanine J had strong interaction with the active site of the inducible nitric oxide synthase (iNOS) protein.

Ionic polymer metal composite (IPMC) always takes big risks of electrode cracking and peeling, which lead to energy wasting, waterloss, and uneven electric field distribution, thus hamper its commercial applications. To address this issue, we propose a facile and effective technique to repair the electrode fatigue by coating polyvinylpyrrolidone (PVP) encapsulated Ag nanoparticles (PVP@AgNPs) on the long-term used IPMC surface. To improve the electrochemical stability, the silver nanoparticles (Ag NPs) with a diameter of ∼34 nm are encapsulated by a 1.3 nm thick PVP film, thus forming a shell-core structure to resist corrosion from the electrolyte solution. Physiochemical investigations reveal that, PVP@AgNPs closely attach to the interior and exterior surfaces of the original Pt nanograin electrode, thus refreshing its electronic conductivity; the repaired IPMC actuator exhibits better electromechanical properties compared to its precursor actuator: 7.62 folds in displacement output, 9.38 folds in force output, and 9.73 folds in stable working time.

Plant cytokinins (CKs) are essential for many central cellular processes and play important roles in the interaction between bacteria and plants. Perception of CK is executed by the CHASE domain in the histidine kinase sensors of a class of two-component regulatory systems. Despite advances in understanding the structural basis for CK perception by the sensor AHK4 in Arabidopsis, the molecular mechanism of CK binding by other sensors is unclear. Here, we report the crystal structure of the CHASE domain in the histidine kinase PcrK of the bacterial plant pathogen Xanthomonas campestris pathovar campestris, which senses plant CK, determined at 2.55 A resolution. The structure reveals that the PcrK has an AHK4-like overall topology and assembles into a homodimer. Strikingly, detailed structural analysis unveils two unique features of the PcrK ligand binding pocket: the size of the pocket is restricted for CK binding, and the PcrK applies a positively charged arginine but not a negatively charged aspartate to recognize the ligand. We propose a model to explain how the PcrK accommodates CK-sized compounds through conformational changes, providing a potential mechanistic framework for understanding ligand recognition by the PcrK.

The Ni-P amorphous alloy was synthesized by chemical reduction, modified by adding element Co, and characterized by XRD, SEM, XPS and DSC. The hydrodeoxygenation (HDO) performance of the amorphous alloy was investigated by hydrodeoxygenation of vanillin to 2-methoxy-4-methylphenol (MMP). It is shown that the synergy between Ni and Co not only contributes to the reduction of Ni, increases the number of active centers of the catalyst, but also improves the dispersion, disorder and thermal stability of the amorphous alloy. Under the optimized reaction conditions: nCo/(nCo + nNi) (molar ratio) = 0.08, H2 partial pressure of 2.0 MPa, reaction temperature of 150°C, reaction time of 180 min, catalyst dosage of 0.05 g, vanillin conversion and the MMP selectivity can reach 100% and 82.7%, respectively. After 5 cycles of the catalyst, the conversion of vanillin remains 100% and the selectivity of MMP decreases to 68.7%.

The interaction between an moving edge dislocation and helium bubble was studied in BCC-Fe using Molecular dynamics（MD）simulation. Edge dislocation passed the bubble via cut mechanism. A step with a length of b is left on both sides of the bubble after dislocation left away. The influence of simulation temperature, defect size and He/V ratio in bubble on critical resolved shear stress (CRSS) for dislocation to shear bubble were investigated. The CRSS increases with increasing defect sizes, and decreases with increasing temperature. When He/V ratio is at the range of 0-1, CRSS depends weakly on the He/V ratio. The estimated obstacle strength of helium bubble based on MD simulations is acceptable and reasonable agreement with one deduced from the dispersion barrier-hardening model applied to experimental results.

Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.

Membrane proteins are crucial for biological processes, and many of them are important to drug targets. Understanding the three-dimensional structures of membrane proteins are essential to evaluate their bio-function and drug design. High-purity membrane proteins are important for structural determination. Membrane proteins have low yields and are difficult to purify because they tend to aggregate. We summarized membrane protein expression systems, vectors, tags, and detergents, which have deposited in the Protein Data Bank (PDB) in recent four-and-a-half years. Escherichia coli is the most expression system for membrane proteins, and HEK293 cells are the most commonly cell lines for human membrane protein expression. The most frequently vectors are pFastBac1 for alpha-helical membrane proteins, pET28a for beta-barrel membrane proteins, and pTRC99a for monotopic membrane proteins. The most used tag for membrane proteins is the 6×His-tag. FLAG commonly used for alpha-helical membrane proteins, Strep and GST for beta- barrel and monotopic membrane proteins, respectively. The detergents and their concentrations used for alpha-helical, beta-barrel, and monotopic membrane proteins are different, and DDM is commonly used for membrane protein purification. It can guide the expression and purification of membrane proteins, thus contributing to their structure and bio function studying.

A spiroconfigured phenothiazine dioxide compound 10-(2- spiro [fluorenyl-9,9′-xanthen])-phenothiazine 5,5-dioxide (SFX-PzO2) was successfully synthesized via C–N cross-coupling with Pd(PPh3)4 as a catalyst, to set up the state-of-the-art models of spiroconfigured phenothiazine dioxide-based small molecular host, which was systemically researched to understand the structure-property relationships deeply to accumulate the increase of device performance rationally and accelerate the commercialization of OLEDs. The high thermal (Td, 394 °C) and morphological stabilities of SFX-PzO2 were obtained due to its rigid spiroconfigured structure and 3D steric hindrance effect. The twisted non-conjugation connection between spiro [fluoren-9,9′-xanthen] and phenothiazine dioxide ensures the compound possesses high triplet energy level (2.87 eV), which is vital to achieve high performance devices. A blue TADF device used SFX-PzO2 as a host with the maximum EQE and lowest driving voltage of 13.9% and 6.5 V at a luminance of 1000 cd m−2, respectively, for phenothiazine dioxide derivative hosted device.

A novel Tb(III) metal–organic framework was synthesized by a multi-layer diffusion method at room temperature. Adjacent Tb(III) ions were connected together by bridging carboxylic groups to construct one-dimensional chains and the metal–organic framework based on these parallel 1D chains was formed through thiophene-2,5-dicarboxylate bridges. UV–Vis and fluorescent emission spectra as well as theoretical calculation showed that organic ligands acted as sensitizers to Tb(III) fluorescence. With the excitation of 325 nm, the emission peaks of this compound were found at 488, 545, 587, and 621 nm which were attributed to 5D4 → 7F6, 5D4 → 7F5, 5D4 → 7F4, and 5D4 → 7F3 transitions, respectively. The quantum yield for solid sample was 36.98% and this compound can emit strong green light in the solid state. One new Tb(III) metal-organic framework was synthesized by a multi-layer diffusion method at room temperature using thiophene-2,5-dicarboxylate as the bridging ligand and investigated by single-crystal structure, UV-Vis absorption, and fluorescent emission.

Two novel compounds, 2-(2-hydroxyethylthio)-5,8-dimethoxy-1,4-naphthoquinone (HEDMNQ) and 2-(6-hydroxyhexylthio)-5,8-dimethoxy-1,4-naphthoquinone (HHDMNQ), were synthesized to investigate the kill effects and mechanism of 1,4-naphthoquinone derivatives in lung cancer cells. The results of the CCK-8 assay showed that HEDMNQ and HHDMNQ had significant cytotoxic effects on A549, NCI-H23, and NCI-H460 NSCLC cells. Flow cytometry and western blot results indicated that HHDMNQ induced A549 cell cycle arrest at the G2/M phase by decreasing the expression levels of cyclin-dependent kinase 1/2 and cyclin B1. Fluorescence microscopy and flow cytometry results indicated that HHDMNQ could induce A549 cell apoptosis, and western blot analysis showed that HHDMNQ induced apoptosis through regulating the mitochondria pathway, as well as the MAPK, STAT3, and NF-κB signalling pathways. Flow cytometry results showed that intracellular reactive oxygen species (ROS) levels were increased after HHDMNQ treatment, and western blot showed that ROS could modulate the intrinsic pathway and MAPK, STAT3, and NF-κB signalling pathways. These effects were blocked by the ROS inhibitor N-acetyl-L-cysteine in A549 cells. Our findings suggest that compared with HEDMNQ, HHDMNQ had the stronger ability to inhibit the cell viability of lung cancer cells and induce apoptosis by regulating the ROS-mediated intrinsic pathway and MAPK/STAT3/NF-κB signalling pathways. Thus, HHDMNQ might be a potential antitumour compound for treating lung cancer.

All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-IXcc) from the Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-IXcc controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-IXcc expression platform not only can repress gene expression in response to SAM binding to SAM-IXcc aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species., Riboswitches consist of an aptamer domain and expression platform, which senses a signal and regulates gene expression, respectively. Here the authors show that the expression platform of a SAM-I riboswitch from the Gram-negative bacteria can sense and bind uncharged an initiator Met tRNA to control the met operon.

The present study aimed to investigate the toxic effects of different amyloidogenic light-chains (LCs) on cardiomyocytes, and demonstrate the differentially expressed genes (DEGs) and signaling pathways that participate in this process. Cultured cardiomyocytes were treated with recombinant κ LC peptide (AL-09) or with serum from a patient diagnosed with multiple myeloma (λ LC) with cardiac involvement. The 6xHis peptide or serum from healthy patients was used as peptide control or serum control, respectively. Cell viability was determined using CCK-8 assay and apoptosis was analyzed by flow cytometry. The DEGs were detected by RNA sequencing (RNA-Seq), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Changes in gene expression levels were confirmed by reverse transcription-quantitative PCR. The cell viability in the AL-09 peptide-treated (0.2 mg/ml) and patient serum-treated (1:10 dilution) cardiomyocytes decreased to 42 and -72% of the corresponding control groups. The extent of cell apoptosis increased in AL-09-treated cardiomyocytes compared with the control group. RNA-Seq showed 256 DEGs co-existed in the two paired groups, including 127 upregulated and 88 downregulated genes. The KEGG pathways for upregulated expressed genes included the ‘TGF-β signaling pathway’, the ‘Hedgehog signaling pathway’, the ‘ErbB signaling pathway’ and ‘lysine degradation’. The higher mRNA expression of bone morphogenetic protein (Bmp) 4, Bmp6, prostaglandin G/H synthase (Ptgs)1, Ptgs2, epiregulin, Tgfa and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 were confirmed. The KEGG pathways of downregulated expressed genes included genes involved with the ‘p53 signaling pathway’ and the ‘cell cycle’. The mRNA expression levels of E3 ubiquitin-protein ligase CCNB1IP1 showed significant downregulation in the AL-09 peptide group compared with those in the 6xHis peptide group. In conclusion, cardiomyocytes treated with amyloidogenic λ and κ LCs presented with decreased cell viability compared with controls. Cell apoptosis increased in κ LC-treated cells compared with controls. The gene expression profiles associated with transforming growth factor-β-bone morphogenetic protein, the receptor tyrosine-protein kinase erbB-2 signaling pathways, prostaglandins, collagen production, the p53 signaling pathway and the cell cycle were altered in light-chain-treated cardiomyocytes.

Due to an extremely low permittivity, silicone based dielectric elastomer actuator (DEA) needs to be triggered by a very high voltage, thus endures the risks of electrical breakdown and creep rupture. To address this problem, polydimethylsiloxane (PDMS) encapsulated carbon black (PCB) particles are filled in a vinylsilane-rich silicone (VRS) to obtain a hybrid PCB/VRS film with enhanced mechanical and insulation properties. The detected Young’s modulus and dielectric permittivity of the hybrid film containing 5.82 vol% PCB increase by 613 and 244% compared to the pure film, respectively. PDMS’ encapsulation effectively prevents the adjacent PCB particles forming conductive networks, thus the resultant PCB/VRS composite presents an enhanced breakdown strength of 63.31 V/μm and an attenuated dielectric loss of 0.078, which benefit DEA working. Triggered by a relatively low electrical field of 7.14 V/μm, the hybrid DEA exhibits better out-of-plane actuations compared to the pure DEA: 1.91-fold in flection amplitude, 2.79-fold in areal strain, and 4.35-fold in force output.

The high concentration of ammonium chloride in the wastewater from the precipitation of rare earth carbonate was studied by an electrolytic method in this paper. The decomposition rate of ammonium ...

Uniform, monodisperse yttrium aluminum garnet (YAG) rhombic dodecahedron micro-crystals were synthesized using coprecipitation and hydrothermal methods. The Na2SO4 as a surfactant was helpful in improving the dispersity of the crystallites and forming well-faceted, micro-sized dodecahedral YAG crystallites. The effect of the reaction time and the solvent has also been studied. The crystal growth mechanism called dissolution/crystallization was determined by analyzing the experimental and simulated results. And the specific well-developed crystal facets in the {110} family have been demonstrated by the theoretical calculation. A higher integrated emission intensity can be achieved for the YAG:Ce crystallites by improving the phase purity, morphology with better developed dodecahedrons, and dispersion. Furthermore, a rather high luminous efficacy (LE = 104.14 lm/W) for the white LED fabricated using the YAG:Ce3+ phosphor prepared in this work was realized. The correlation between the crystal growth, morphology and luminescence properties of YAG crystallites has been established, which exhibits a great importance for the synthesis and application of mono-dispersed YAG crystallites.

The synthesis of methionine is critical for most bacteria. It is known that cellular methionine has a feedback effect on the expression of met genes involved in de novo methionine biosynthesis. Previous studies revealed that Gram-negative bacteria control met gene expression at the transcriptional level by regulator proteins, while most Gram-positive bacteria regulate met genes at post-transcriptional level by RNA regulators (riboregulators) located in the 5′UTR of met genes. However, despite its importance, the methionine biosynthesis pathway in the Gram-negative Xanthomonas genus that includes many important plant pathogens is completely uncharacterized. Here, we address this issue using the crucifer black rot pathogen Xanthomonas campestris pv. campestris (Xcc), a model bacterium in microbe–plant interaction studies. The work identified an operon (met) involved in de novo methionine biosynthesis in Xcc. Disruption of the operon resulted in defective growth in methionine-limited media and in planta. Western blot analysis revealed that the expression of the operon is dependent on methionine levels. Further molecular analyses demonstrated that the 5′UTR, but not the promoter of the operon, is involved in feedback regulation on operon expression in response to methionine availability, providing an example of a Gram-negative bacterium utilizing a 5′UTR region to control the expression of the genes involved in methionine biosynthesis.

Neointimal hyperplasia as a consequence of vascular injury is aggravated by inflammatory reaction and oxidative stress. The α7 nicotinic acetylcholine receptor (α7nAChR) is a orchestrator of cholinergic anti-inflammatory pathway (CAP), which refers to a physiological neuro-immune mechanism that restricts inflammation. Here, we investigated the potential role of CAP in neointimal hyperplasia using α7nAChR knockout (KO) mice. Male α7nAChR-KO mice and their wild-type control mice (WT) were subjected to wire injury in left common carotid artery. At 4 weeks post injury, the injured aortae were isolated for examination. The neointimal hyperplasia after wire injury was significantly aggravated in α7nAChR-KO mice compared with WT mice. The α7nAChR-KO mice had increased collagen contents and vascular smooth muscle cells (VSMCs) amount. Moreover, the inflammation was significantly enhanced in the neointima of α7nAChR-KO mice relative to WT mice, evidenced by the increased expression of tumor necrosis factor-α/interleukin-1β, and macrophage infiltration. Meanwhile, the chemokines chemokine (C-C motif) ligand 2 and chemokine (CXC motif) ligand 2 expression was also augmented in the neointima of α7nAChR-KO mice compared with WT mice. Additionally, the depletion of superoxide dismutase (SOD) and reduced glutathione (GSH), and the upregulation of 3-nitrotyrosine, malondialdehyde and myeloperoxidase were more pronounced in neointima of α7nAChR-KO mice compared with WT mice. Accordingly, the protein expression of NADPH oxidase 1 (Nox1), Nox2 and Nox4, was also higher in neointima of α7nAChR-KO mice compared with WT mice. Finally, pharmacologically activation of CAP with a selective α7nAChR agonist PNU-282987, significantly reduced neointima formation, arterial inflammation and oxidative stress after vascular injury in C57BL/6 mice. In conclusion, our results demonstrate that α7nAChR-mediated CAP is a neuro-physiological mechanism that inhibits neointima formation after vascular injury via suppressing arterial inflammation and oxidative stress. Further, these results imply that targeting α7nAChR may be a promising interventional strategy for in-stent stenosis.

Min pigs and Large White pigs are two breeds that vary significantly in thickness of adipose tissue. In this study, transcriptome profiling was used to examine the fat tissues of both breed...

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2+ macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease. Electronic supplementary material The online version of this article (10.1007/s13238-018-0527-6) contains supplementary material, which is available to authorized users.

A novel ion-exchange polymer-metal composite (IPMC) actuator is fabricated by sandwiching sulfonated fluorene blocked polysulfone (SDPF- b -PSU) between two Pt nanograin sheets. With increased concentration of chlorosulfonic acid, the SDPF- b -PSU film with more sulfonic groups exhibits strong ion exchange capacity, high Li + ion conductivity, and ordered phase separation, which may contain an increased number of cations and possess larger and better interconnected inner channels for ion migration, thus providing the power to produce large force and power outputs. The SDPF- b -PSU film also exhibits enhanced mechanical performance and water uptake when compared to the pure Nafion film, providing a strong, hydrated matrix to support IPMC functions. At the driving voltage of 4 V, the SDPF- b -PSU actuator exhibits a strong force output which is 11 folds higher than that of the pure Nafion actuator.

The effect of genistein on Bcl-2 and Bax protein expression in the ovarian tissue of rats with polycystic ovarian syndrome (PCOS) was evaluated. Sixty rats were divided into six groups. Rats in the Dose group received genistein at a concentration of either 5 (L-gen), 10 (M-Gen) or 20 (H-Gen) mg per kg of body weight per day. The expression of Bcl-2 mRNA and Bax mRNA was determined by in situ hybridization. Bcl-2 and Bax protein concentration was quantified by ELISA. The results showed that the expression of Bcl-2 mRNA and Bcl-2 protein was significantly higher in the high genistein Dose group (H-Gen) when compared to the Model group (MG) (P

Background/Aims: Loss of endothelial barrier function plays an important role in the development of ventilator-induced lung injury (VILI). This study aimed to investigate the effects of miR135a on VILI in a model of mechanical stretch (MS)-induced human umbilical vein endothelial cell (HUVEC) injury. Methods: HUVECs were randomly assigned to 7 groups: blank, negative control (NC), NC+MS, miR135a over-expression (mi-miR135a), mi-miR135a + MS, miR135a silencing (si-miR135a) and si-miR135a + MS groups. MS was induced by subjecting cells to cyclic stretch at 20% stretch for 4 h. After 24 h, levels of reactive oxygen species (ROS) were measured by DCFH-DA fluorescence intensity. Apoptosis was measured using annexin V-FITC/propidium iodide assay with flow cytometry. Inflammatory cytokine levels were determined by ELISA. Barrier integrity was determined using FITC-conjugated dextran assay. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2 and Bax were examined using western blotting. The interaction between miR135a and PHLPP2 was evaluated by dual-luciferase reporter assay. Results: Our results showed that MS reduced cell numbers, increased the number of apoptotic cells, increased ROS, barrier dysfunction and inflammatory cytokines in HUVECs, and reduced p-PI3K and p-Akt expression; silencing of miR135a worsened MS-induced HUVEC injury. However, miR135a over-expression protected HUVECs against MS-induced increases in apoptotic cells, ROS, barrier dysfunction and inflammatory cytokines, which were accompanied by activation of the PI3K/Akt signaling pathway. Simultaneous silencing of miR135a and PHLPP2 partially salvaged the effects of miR135a silencing, and miR135a was found to interact with PHLPP2. Conclusion: miR135a may protect HUVECs from MS-induced injury by inhibiting PHLPP2 to activate PI3k/Akt signaling pathway.

Excessive manganese (Mn) accumulation in the brain may induce an extrapyramidal disorder known as manganism. Inflammatory processes play a critical role in neurodegenerative diseases. Therapeutically, non-steroidal anti-inflammatory drugs or analogous anti-inflammatory therapies have neuroprotective effects. As a non-steroidal anti-inflammatory drug, p-aminosalicylic acid (PAS) has anti-inflammatory effects, which are mediated by decreased prostaglandins E2 (PGE2) levels. The aim of the current study was to investigate whether PAS-Na treatment prevents Mn-induced behavioral changes and neuroinflammation in vivo. Male Sprague-Dawley rats were intraperitoneally (i.p.) injected with MnCl2·4H2O (15mg/kg) for 12 weeks, followed by 6 weeks PAS-Na treatment. Sub-chronic Mn exposure increased Mn levels in the whole blood, cortex, hippocampus and thalamus, and induced learning and memory deficits, concomitant with astrocytes activation in the cortex, hippocampus and thalamus. Moreover inflammatory cytokine levels in serum and brain of Mn-treated group were increased, including IL-1β, IL-6, TNF-αand PGE2, especially in the hippocampus and thalamus. Furthermore, sub-chronic Mn exposure also increased inflammatory cytokines and COX-2 in transcription levels concomitant with increased MAPK signaling and COX-2 in the same selected brain regions. PAS-Na treatment at the highest doses also decreased Mn levels in the whole blood and selected brain tissues, and reversed the Mn-induced learning and memory deficits. PAS-Na inhibited astrocyte activation as well as the Mn-induced increase in inflammatory cytokine levels, reducing p38, ERK MAPK pathway and COX-2 activity. In contrast PAS-Na had no effects on the JNK MAPK pathway. These data establish the efficacy of PAS-Na not only as a chelating agent to mobilize whole blood Mn, but also as an anti-inflammatory agent.

Plasma electrolytic oxidation (PEO) and a subsequent direct electroless nickel (EN) plating were carried out on magnesium (Mg) alloy AZ31B. The influences of additives of fluoride ions in the electrolyte on the growth of PEO/Ni-P composite coating were investigated. Results show that addition of fluoride ions in the electrolyte plays a dual role in the formation of PEO coating, i.e. uniformly increasing the thickness of PEO coating and the compactness of inner layer. Fluoride is enriched in the inner PEO layer as an amorphous phase. For the subsequent EN plating, extension of PEO time is beneficial to the deposition of Ni P layer, whilst fluoride ions in the PEO electrolyte are detrimental to the direct EN plating. It is evident that Ni P nodules selectively nucleate and grow in the micro-pores of the PEO layer. Electrochemical tests reveal that the PEO/Ni-P composite coating provides superior corrosion protection to the underlying Mg substrate. A nucleation mechanism of the Ni P nodules on the PEO layer was proposed.

In order to solve the problem of low sample forming efficiency and uncontrollable crystal type in inkjet printing, a formula of explosive ink suitable for micro-spraying is designed by using hexanitrohexaazaisowurtzitane (CL-20) as the main explosive, the compound of polyazide glycidyl ether and ethyl cellulose as the bonding system, ethyl acetate as the solvent, and the refined e-CL-20 as the seed crystal in this paper. The optimal process conditions were determined, and under the optimal process conditions, the explosive ink is written on an aluminum substrate or a glass substrate by micro-spraying direct writing technology, and CL-20 based energetic thin film forming samples are characterized. The results show that the CL-20 crystal form in the sample is e type and the molding effect is good. The optimum process conditions are as follows: the nozzle has an air pressure of 0.02 MPa, the height is 40 mm, the spraying rate is 0.4 ml min−1, and the substrate temperature is 50°C. The explosive particles in the energetic thin films are spherical. The particle size is about 10 µm, and the particle size distribution is relatively uniform. The density of the composite is 1.567 g cm−3, and the molding density can reach 80.2% of the theoretical density. The activation energy is 242.07 kJ mol−1. The characteristic drop height H50 is 38.5 cm. When the charge width is 0.8 mm, the critical size of the detonation is 0.8 × 0.03 mm2. The detonation wave formed after the shaped sample is detonated in a small groove with a cross-sectional dimension of 1.0 × 1.0 mm2 can successfully pass through multiple continuous 90° charging corners.

// Ying Wang 1, 4 , Xue Han 2 , Yan Dong Li 3 , Yabing Wang 2 , Shi Yang Zhao 2 , Dong Jie Zhang 1 and Yu Lu 5 1 College of Food, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China 2 College of Biological Science and Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, PR China 3 Hebei Institute of Veterinary Drugs Control, Shijiazhuang 050000, PR China 4 National Coarse Cereals Engineering Research Center, Daqing 163319, PR China 5 Huabei Petroleum Administration Bureau, Huasheng Integrated Service, Tianjin 300000, PR China Correspondence to: Xue Han, email: hanxue_h@163.com Keywords: lentinan; dose dependence; liver cancer; immunoprophylaxis; promotion Received: March 12, 2017 Accepted: April 21, 2017 Published: August 01, 2017 ABSTRACT Lentinan could exhibit significant biological activity favorable for human health and disease control such as the recovery of patients with liver cancer. In order to investigate the effect of lentinan dose dependence between immunoprophylaxis and promotion of cancer cell proliferation of the murine liver cancer, different concentrations of lentinan were prepared for the test in vitro (MTT assay) and in vivo (cumulative survival assay, spleen lymphocyte proliferation tests and peritoneal macrophage phagocytosis assays). New emerging proteins of the H22 cell incubated with lentinan was demonstrated by MS analysis and protein database searching. Lentinan was non-toxic for HL7702 cells but inhibited H22 cells proliferation obviously in a dose-dependent manner. In vivo , the proliferation of H22 hepatocarcinoma cells was inhibited by lentinan 0.4mg/kg body weight (L2, survival rate, 20%, P