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Objective: The contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. Using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes.Research Design and Methods: About 2% of LEW*1WR1 rats develop spontaneous autoimmune diabetes, but disease penetrance is much higher if weanling rats are exposed to environmental perturbants including Kilham rat virus (KRV). We compared KRV with other viruses for diabetogenic activity.Results: Both KRV and rat cytomegalovirus (RCMV) induced diabetes in up to 60% of LEW*1WR1 rats, whereas H-1, vaccinia, and Coxsackie B4 viruses did not. Simultaneous inoculation of KRV and RCMV induced diabetes in 100% of animals. Pretreatment of rats with an activator of innate immunity increased the diabetogenicity of KRV but not RCMV and was associated with a moderate rate of diabetes after Coxsackie B4 and vaccinia virus infection. Inoculation of LEW*1WR1 dams with both KRV and RCMV prior to pregnancy protected weanling progeny from virus-induced diabetes in a virus-specific manner.Conclusions: Exposure to viruses can affect the penetrance of autoimmune diabetes in genetically susceptible animals. The diabetogenicity of infection is virus specific and is modified by immunomodulation prior to inoculation. Maternal immunization protects weanlings from virus-induced diabetes, suggesting that modification of immune responses to infection could provide a means of preventing islet autoimmunity. [ABSTRACT FROM AUTHOR]

The article presents a study on human cytomegalovirus, a pathogen that can cause life-threatening diseases. It notes that this ubiquitous beta-herpes virus carries regulatory proteins such as IE72 and IE82 during infections that affects the majority of population. It states that with this, a Tet-On system was used to measure the effect of IE86 on apoptosis. The result shows inhibition of tumor necrosis factor of IE86 and IE86 does not affect micro RNA level.

Abstract: There are two species under the monograph of Radix Paeoniae Rubrae (“Chi-shao” in Chinese) in Chinese Pharmacopoeia 2005 edition-Paeonia lactiflora Pallas and Paeonia veitchii Lynch. Due to different species and growing conditions, there are significant chemical differences between the two species, which may result in the improper clinical usage under the same name. Chemical pattern expressed by high performance liquid chromatographic (HPLC) fingerprint analysis can play an important role in species differentiation and quality control of Radix Paeoniae Rubra. In the present work, HPLC fingerprints of two kinds of Radix Paeoniae Rubra have been established and analysed with chemometric methods including similarity evaluation and principal component analysis. Both of the fingerprint common patterns of the two species comprise 13 characteristic peaks, nine of which were common peaks of the two species. However, significant differences between the roots of P. veitchii and P. lactiflora exist not only in the content of certain constituents, especially phenolic acids but also in peak-to-peak ratios expressed by the fingerprint patterns. According to the recent pharmacological studies on polyphenolic constituents, root originating from P. veitchii may possess better efficacy and quality than that from P. lactiflora. Our research reveals that further pharmacological investigation is very necessary to determine whether the two species should be embodied under the same monograph in Chinese Pharmacopoeia. [Copyright &y& Elsevier]

Abstract: A series of Thiazole Orange (TO) derivatives were synthesized and modified by introducing different substitutional groups on benzothiazole and 4-methylquinoline All the TO derivatives were confirmed by 1HNMR and MS. TO derivative bearing NH2– was modified by folic acid and used to label breast cancer cells. The phenomenon of fluorescence enhancement was shown by the fluorescence spectrums of TO derivatives and micrographs of the labeled breast cancer cells. It offered a new try in the aspect of labeling cells by the embedded dyes. [Copyright &y& Elsevier]

Abstract: The North China Plain (NCP) is one of the most water stressed areas in the world. The water consumption of winter wheat accounts for more than 50% of the total water consumption in this region. An accurate estimate of the evapotranspiration (ET) and crop water productivity (CWP) at regional scale is therefore key to the practice of water-saving agriculture in NCP. In this research, the ET and CWP of winter wheat in 83 counties during October 2003 to June 2004 in NCP were estimated using the remote sensing data. The daily ET was calculated using SEBAL model with NOAA remote sensing data in 17 non-cloud days whereas the reference daily crop ET was estimated using meteorological data based on Hargreaves approach. The daily ET and the total ET over the entire growing season of winter wheat were obtained using crop coefficient interpolation approach. The calculated average and maximum water consumption of winter wheat in these 83 counties were 424 and 475mm, respectively. The calculated daily ET from SEBAL model showed good match with the observed data collected in a Lysimeter. The error of ET estimation over the entire growing stage of winter wheat was approximately 4.3%. The highest CWP across this region was 1.67kgm−3, and the lowest was less than 0.5kgm−3. We observed a close linear relationship between CWP and yield. We also observed that the continuing increase of ET leads to a peaking and subsequent decline of CWP, which suggests that the higher water consumption does not necessarily lead to a higher yield. [Copyright &y& Elsevier]

Due to rock masses' nonlinear failure property, it is inappropriate to investigate the stability of rock slopes using the traditional SRM (strength reduction method) which is based on the linear MC (Mohr-Coulomb) failure criterion. To conduct 3D analysis (three dimensional) of rock slopes, we propose a 3D-NSRNMM (3D nonlinear strength reduction numerical manifold method) that is based on the nonlinear GHB (Generalized Hoek-Brown) failure criterion. To effectively implement the proposed 3D-NSRNMM, two methods are adopted to convert the GHB parameters into the average and instantaneous equivalent MC parameters. With the proposed 3D-NSRNMM, the influences of different types of equivalent MC parameters, and boundary conditions on rock slopes' stability are investigated. The numerical results assessed from the proposed 3D-NSRNMM indicate that: 1) boundary conditions will significantly influence the safety factor and failure mode of a rock slope obtained from 3D analysis; 2) the safety factor from two-dimensional analysis is more conservative compared with 3D analysis; 3) Furthermore, safety factors based on the instantaneous equivalent MC parameters are very close to those based on the average equivalent MC parameters, but 3D rock slopes' failure modes based on the two different types of equivalent MC parameters are a little different from each other. • A 3D-NSRNMM that is on the basis of the nonlinear GHB criterion is proposed. • Two methods are adopted to convert GHB parameters into equivalent MC parameters. • Stability analyses of 3D rock slopes are investigated using the 3D-NSRNMM. • Boundary conditions significantly influence the safety factor and failure mode of 3D rock slopes. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) transporter C10 (ABCC10), also named multidrug resistance protein 7 (MRP7), is a member of ABC transporter superfamily and has been revealed to transport a wide range of chemotherapeutic agents including taxanes, epothilone B, Vinca alkaloids, and anthracyclines. In our previous study, a 5-cyano-6-phenylpyrimidin derivative CP55 was synthesized and found significantly reversal effect of multidrug resistance (MDR) mediated by ABCB1. In this study, we found CP55 also efficiently reversed MDR mediated by ABCC10. Our in vitro study showed that co-treatment with CP55 significantly increased the efficacy of ABCC10-substrate anticancer drugs in MDR cells overexpressing ABCC10. Furthermore, we showed that treatment with CP55 increased the intracellular accumulation of [3H]-labeled anticancer drugs and in-turn decreasing drug efflux by inhibiting the transport activity, without altering ABCC10 protein ex-pression level or cellular localization. Potential CP55-ABCC10 interactions were predicted via docking analysis using human ABCC10 homology model and obtained high docking score. Therefore, CP55 represents a promising therapeutic agent in the combinational treatment of chemo-resistant cancer related to ABCC10. Proposed mechanism of CP55 in inhibiting the multidrug resistance mediated by ABCC10 in cancer cells. [Display omitted] • Multidrug resistance (MDR) in cancer is one of the major obstacles in chemotherapy. • ABCC10 mediates resistance to wide spectrum of chemotherapeutic agents, but only limited number of studies are available. • Overexpression of ABCC10 has been linked to various types of cancers including colorectal, gastric and lung cancer. • CP55 is a potent ABCC10 inhibitor which enhances the anticancer drug sensitivity in ABCC10-overexpression MDR cells. [ABSTRACT FROM AUTHOR]

Proposed mechanism of CMP25 in inhibiting the multidrug resistance mediated by MRP7/ABCC10 in cancer cells. [Display omitted] Multidrug resistance-associated protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to mediate the cross-membrane translocation of a wide range of chemotherapeutic agents including taxanes, epothilones, Vinca alkaloids, Anthracyclines and Epipodophyllotoxins. In our previous study, a 1,2,3-triazole-pyrimidine hybrid CMP25 was synthesized and found able to efficiently reverse multidrug resistance (MDR) mediated by P-glycoprotein. In this study, we evaluated the efficacy of compound CMP25 in reversing MDR mediated by MRP7 in vitro. The results showed that CMP25 significantly sensitized MRP7-overexpressing cells to anticancer drugs that are MRP7 substrates. Mechanistic study showed that CMP25 reversed MRP7-mediated MDR by increasing the intracellular accumulation of anticancer drugs and decreasing drug efflux, without altering protein expression level or subcellular localization. Currently, very few studies on synthetic MRP7 modulators have been published. Our findings provide a valuable prototype for designing drugs to combine with conventional anticancer drugs to overcome MDR-mediated by MRP7. [ABSTRACT FROM AUTHOR]

• Novel interconnector replaces straight channel to improve SOFC performance. • Novel interconnector enhances disturbance and improves the gas velocity and vorticity. • Novel interconnector eliminates the limitation of ribs on gas diffusion. • Novel interconnector shortens the charge transfer path in SOFC. • Novel interconnector reduces activation, concentration, and contact overpotentials. This study proposes a novel interconnector, termed beam and slot interconnector (BSI), for the anode-supported planar solid oxide fuel cell (SOFC). A detailed comparative investigation is conducted on various transport characteristics and electrical performance of the SOFC stacks with conventional straight channel interconnectors (SCIs) or with novel interconnectors. Results show that the peak power density of a SOFC stack with BSIs is 24.8% higher than it with SCIs at 700 °C and a fuel–air flow rate of 16–40 Nml/(min·cm2). Moreover, BSI can reduce the fuel–air feeding and enhance the fuel–air utilization while maintaining high output power density. Compared with SCI, BSI promotes the gas disturbance, significantly increases the gas velocity and vorticity, and leads the gas to flow in the direction perpendicular to the channel. BSI eliminates the limitation of SCIs on gas diffusion in the electrode and transfers sufficient reactant gas into the electrode function layers for electrochemical reactions. BSI shortens the charge transfer path in SOFC and almost avoids the adverse effects of the electrode-interconnector contact resistance. Compared with the conventional SOFC stack, the novel SOFC stack with BSIs significantly reduces various overpotentials. At 700 °C and 0.5 A/cm2, the activation, concentration, and contact overpotentials are reduced by 8.5%, 47.4%, and 96.4% respectively, and the total overpotential finally drops by 20.0%. Overall, the electrical performance of the SOFC stack with novel interconnectors significantly exceeds the one with conventional interconnectors under the same operating conditions. [ABSTRACT FROM AUTHOR]

This study was undertaken to evaluate the effect of topical administration of Rubus suavissimus S. Lee (Rosaceae) (RUS), an extract of Chinese sweet leaf tea, in the prevention of experimentally induced corneal neovascularization. Corneal neovascularization was induced in 40 rat eyes (1 per animal) by a silver nitrate cauterization technique. Three concentrations (0.1%, 1%, and 10% w/v) of RUS in saline were administered topically twice a day for 7 days. The coverage of the corneal surface by neovascular vessels was measured, using photographs, as a percentage of total cornea area. A histopathologic score was assigned to each cornea. The difference in mean burn stimulus scores of treatment and placebo groups was not statistically significant (p = 0.714). The 10% RUS solution caused a significant decrease in the percentage of neovascularization in response to cauterization (p < 0.01); the 0.1% and 1% concentrations were not significantly different from controls (p = 0.173). The 10% concentration group had significantly less neovascularization than the control group (p < 0.01). It was found that topical application of 10% RUS solution caused a significant decrease in neovascular response to silver nitrate cauterization compared with control eyes. [ABSTRACT FROM AUTHOR]

Abstract: Hydro-distillated volatile oils of Ephedra sinica Stapf. from six populations of Inner Mongolia in Northeastern China were analyzed by using GC/MS. Ninety-nine compounds were identified in the oils and a relatively high variation in their contents was found. The main constituents of the essential oils were α-terpineol (19.28–52.23%), p-vinylanisole (0.59–11.64%), 3-methyl-2-buten-1-ol (0–5.44%), tetramethylpyrazine (0.63–8.99%), terpine-4-ol (1.17–4.37%), α-linalool (1.62–5.15%), phytol (1.24–15.73%), γ-eudesmol (0–7.77%), and eudesm-7(11)-en-4-ol (0.41–6.13). Six populations were divided into two chemotypes based on cluster analysis and principal component analysis (PCA); one rich in α-terpineol and p-vinylanisole, and the other rich in phytol, γ-eudesmol, and eudesm-7(11)-en-4-ol. [Copyright &y& Elsevier]

Hydrodistilled leaf oils of Pistacia chinensis Bunge from five locations in China were analyzed using GC/MS. A total of 58 compounds was identified in the oils, and a relatively high variation in their contents was found. The major compounds include β-phellandrene (0.54–53.86%), α-pinene (4.74–54.44%), β-pinene (0.49–42.90%), caryophyllene (5.64–20.01%), cis-ocimene (tr−43.93%), eudesmadiene (0–15.06%), and camphene (tr−20.57%). Cluster analysis classified the leaf oils into two chemotypes: one rich in α-pinene and β-pinene, and the other rich in β-phellandrene. [ABSTRACT FROM AUTHOR]

Volatiles were distilled from leaves of three Bergenia species collected from Yunnan, Xinjiang and Tibet in western China and analyzed using GC/MS instrumentation. The contents of extractable volatiles varied substantially among the three species with B. crassifolia having approximately 0.05% dry wt (v/w), B. purpurscens 0.01% (v/w) and B. stracheyi 0.13% (v/w), respectively. In B. crassifolia, the main components were present as 3-methyl-2-buten-1-ol (26.56%), hexadecanoic acid (16.06%), dodecanoic acid (9.99%), linalool (5.63%) and octadecadienoic acid (4.10%). In B. purpurascens, the main components were β-eudesmol (18.63%), phytol (14.50%), hexadecanoic acid (13.05%), n-nonacosane (9.19%) and 3-methyl-2-buten-1-ol (7.52%). In B. stracheyi, 3-methyl-2-buten-1-ol was the dominant sort of volatile (52.71%), whereas detected major constituents included β-eudesmol (7.44%), damascenone (3.22%), caryophyllene (2.75%) and phytol (2.57%). Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Leaf extract of Rubus suavissimus S. Lee (Rosaceae), a perennial woody shrub indigenous to southern China, was tested for its biological activity in the regulation of transcription factor NF-κB (nuclear factor kappa B) A NF-κB luciferase reporter cell line was used in this study. The crude extract inhibited NF-κB at 100–1000 µg/ml concentrations with minor cytotoxicity. This finding prompted two more rounds of fractionation toward separating the active fraction from the cytotoxic fraction. Five fractions were obtained in the first round of fractionation, of which RUS-C20 was found to be the most potent in inhibiting NF-κB without signs of cytotoxicity up to 1000 µg/ml concentration. Fraction RUS-C100 showed little inhibition to NF-κB and apparent cytotoxicity. Further fractionation of RUS-C20, using Sephadex LH-20 chromatography, resulted in three subfractions that were distinct in chemical constituents as determined by their retention times and UV absorption spectra of each component. NF-κB reporter assay indicated that one of the three subfractions of RUS-C20 retained the inhibitory activity, whereas the other two subfractions were inactive. Bioassay-guided fractionation led to a successful separation of efficacy from cytotoxicity and identification of active components. This warrants further isolation for a purified single compound, which can be used as the chemical marker to standardize the extract for inhibition of NF-κB. [ABSTRACT FROM AUTHOR]

Abstract: Using mtDNA sequencing and allozyme electrophoresis data, we tested the “vicariance followed by dispersal” hypothesis of the Bufo gargarizans species group and re-evaluated the species status in the general lineages species concept. A phylogenetic analysis suggested that dispersal, instead of vicariance, dominated the history of the species group. There was a general trend of west to east dispersal, while some lineages from the east subsequently returned to the west. The secondary admixture of those previously allopatric lineages produced substantial levels of sympatric genetic diversity, often as high as 7.0% pairwise difference within populations. The phylogenetic hypothesis does not support the current two species designation. Neither B. andrewsi nor B. gargarizans represents an independent evolutionary lineage, and monophyletic groups did not correspond to geographically discrete groups. Allozyme data also failed to reveal any fixed allelic difference among the populations. Therefore, we recommend regarding the complex as a single species, Bufo gargarizans, without subspecies division. [Copyright &y& Elsevier]

The treatment of sepsis is still challenging and the liver is an important target of sepsis-related injury. Macrophages are important innate immune cells in liver, and modulation of macrophages M1/M2 polarization may be a promising strategy for septic liver injury treatment. Macrophage polarization and inflammation of liver tissue has been shown regulated by pyruvate kinase M2 (PKM2)-mediated aerobic glycolysis and immune inflammatory pathways. Therefore, modulating PKM2-mediated immunometabolic reprogramming presents a novel strategy for inflammation-associated diseases. In this study, cynaroside, a flavonoid compound, promoted macrophage phenotypic transition from pro-inflammatory M1 to anti-inflammatory M2, and mitigated sepsis-associated liver inflammatory damage. We established that cynaroside reduced binding of PKM2 to hypoxia-inducible factor-1α (HIF-1α) by abolishing translocation of PKM2 to the nucleus and promoting PKM2 tetramer formation, as well as suppressing phosphorylation of PKM2 at Y105 in vivo and in vitro. Moreover, cynaroside restored pyruvate kinase activity, inhibited glycolysis-related proteins including PFKFB3, HK2 and HIF-1α, and inhibited glycolysis-related hyperacetylation of HMGB1 in septic liver. Therefore, this study reports a novel function of cynaroside in hepatic macrophage polarization, and cecum ligation and puncture-induced liver injury in septic mice. The findings provide crucial information with regard to therapeutic efficacy of cynaroside in the treatment of sepsis. [Display omitted] [ABSTRACT FROM AUTHOR]

• Binder free electrode composed of Cu 2 O/CuO/Cu/Carbon-polymer fibers are synthesized by a facile anodic electrochemical deposition method. • The Cu 2 O/CuO are uniformly dispersed on the surface of polymer fibers with fluffy morphology, which is very beneficial to the transport of Li+. • The Cu 2 O/CuO/Cu/Caron-polymer electrode exhibits excellent properties such as high capacities, good cycling stabilities and rate capacities. • The facile anodic electrochemical deposition method adopted in this work is simple, green and inexpensive. ga1 Design of Cu 2 O/CuO nanocomposites as anode materials for lithium-ion batteries has attracted extensive attention because of their potential applications in the energy field. Herein, in this work, the coordination polymers of Cu2+ and flexible chain-like α, ω-dicarboxylate (succinate and sebacate) are synthesized by a facile anodic electrochemical deposition method, in which succinic acid/sebacic acid is used as electrolyte and the copper foil is used as electrodes. The obtained Cu(α, ω-dicarboxylate) polymers grown on copper foil substrate are decomposed and oxidized to prepare a Cu 2 O/CuO/Cu/Carbon-polymer composite fibers, in which the nanoparticles of Cu 2 O/CuO/Cu are uniformly incorporated into a fibrous carbon-polymer, which can facilitate Li+ ion diffusion to active sites in the electrodes and alleviate the volume expansion during the charge and discharge process. As a result, the Cu 2 O/CuO/Cu/Carbon-polymer composite fibers can be used as novel binder free anode materials for lithium-ion batteries, which displays high capacity, excellent cycle stability and rate performance. The initial discharge capacity of composite fibers electrode derived from Cu (sebacate) polymers (Cu-C10) is as high as 508.9 mAh/g at the current densities of 50 mA·g−1. After 150 cycles, the capacity can still remain at 479.9 mAh/g with capacity retention rate of 94.3%. The preparation of electrodes by novel electrochemical deposition in this work would provide a new insight for preparing advanced binder free metal oxide/carbon-based anodes for LIBs with environmental friendliness and inexpensive. [ABSTRACT FROM AUTHOR]

[Display omitted] • Conjugation of GABA make 5b more active anti-depressant. • 5b was a better modulator on programmed cell apoptosis than DHA. • 5b was able to modulate Akt, while DHA could not. • 5b maintained activity to induce neurite outgrowth and cell differentiation. Three hybrids of dihydro-artemisinin (DHA) with β-aminopropionic acid, γ-aminobutyric acid, and histamine have been designed and synthesized. The conjugate of DHA with GABA labelled as 5b was confirmed the most active candidate against both Cort- and SNP-induced PC12 cell impairments with EC 50 value of 8.04 ± 0.35, and 9.38 ± 0.56 μM, respectively. 5b was clearly highlighted as a good modulator on protein expression of Akt, Bcl-2, and Bax, indicating its functions against programmed cell apoptosis. 5b significantly reversed the Cort-induced excessive calcium influx and release from internal organelles. It was demonstrated the ability to express increased levels of β-tubulin III and to up-regulate phosphorylation level of cAMP response element-binding protein (CREB), leading to cell differentiation. It can penetrate blood − brain barrier (BBB) with propriate stability. Altogether, these data strongly support that 5b is a potential anti-depressant. [ABSTRACT FROM AUTHOR]

[Display omitted] • A modified Ni-particle coarsening model for predicting the degradation of SOFC. • Evolution of microstructure parameters over time is quantified. • A fully-coupled model is developed for long-term DIR-SOFC. • Optimal operating conditions for improved performance and stability. Long-term stability and durability of solid oxide fuel cell (SOFC) are the major challenges for fuel flexibility and commercialization. In this study, a fully coupled multi-field model is developed by coupling a modified Ni-particle coarsening model and a microstructure model for predicting the performance degradation of methane direct reforming (DIR) SOFC due to Ni-particle coarsening. The effect of Ni-particle coarsening on percolation probability of Ni-particle, effective TPB area, effective electron-conductivity, maximum power density, and the degradation rate of DIR-SOFC are quantitatively investigated under different operating conditions. The results indicate that to enhance the electrical performance and to reduce the degradation rate, the optima of the operating conditions and anode microstructure for the long-term DIR-SOFC are as follows: 750 °C for the cell operating temperature, 1.0 for anode inlet steam to carbon ratio (S/C), 0.3 A/cm2 for the operating current density, and corresponding to Ni-particle with an initial diameter of 0.6 μm, the optimal YSZ-particle diameter is 1.0 μm. [ABSTRACT FROM AUTHOR]

Aha1 is the only co-chaperone known to strongly stimulate the ATPase activity of Hsp90. Meanwhile, besides the well-studied co-chaperone function, human Aha1 has also been demonstrated to exhibit chaperoning activity against stress-denatured proteins. To provide structural insights for a better understanding of Aha1's co-chaperone and chaperone-like activities, nuclear magnetic resonance (NMR) techniques were used to reveal the unique structure and internal dynamics features of full-length human Aha1. We then found that, in solution, both the two domains of Aha1 presented distinctive thermal stabilities and dynamics behaviors defined by their primary sequences and three-dimensional structures. The low thermal stability (melting temperature of Aha128–162: 54.45 °C) and the internal dynamics featured with slow motions on the µs-ms time scale were detected for Aha1's N-terminal domain (Aha1N). The aforementioned experimental results suggest that Aha1N is in an energy-unfavorable state, which would therefore thermostatically favor the interaction of Aha1N with its partner proteins such as Hsp90's middle domain. Differently from Aha1N, Aha1C (Aha1's C-terminal domain) exhibited enhanced thermal stability (melting temperature of Aha1204–335: 72.41 °C) and the internal dynamics featured with intermediate motions on the ps-ns time scale. Aha1C's thermal and structural stabilities make it competent for the stabilization of the exposed hydrophobic groove of dimerized Hsp90's N-terminal domain. Of note, according to the NMR data and the thermal shift results, although the very N-terminal region (M1-W27) and the C-terminal relaxin-like factor (RLF) motif showed no tight contacts with the remaining parts of human Aha1, they were identified to play important roles in the recognition of intrinsically disordered pathological α-synuclein. [ABSTRACT FROM AUTHOR]

• Tubular PCFC with effective area of 2.3 cm2 is fabricated by dip-coating technique. • It shows high performance at reduced temperature, giving 465 mW cm−2 at 600 °C. • The cell outputs 118 mW cm−2 at 450 °C and reveals detectable power at 200 °C, 3 mW. • Cell stability is tested for 30 h, at a constant voltage of 0.7 V under 600 °C. • Performance declines first and then tend to be stable during stability test. An anode-supported tubular protonic ceramic fuel cell with BaCe 0.7 Zr 0.1 Y 0.2 O 3-δ electrolyte is fabricated using dip-coating technique. Electrochemical performances of the cell are tested at temperatures from 600 to 200 °C, utilizing humidified H 2 (3 vol% H 2 O) as fuel and ambient air as oxidant. With an effective area of 2.3 cm2, the cell yields a peak power density of 465 mW cm−2 at 600 °C and 118 mW cm−2 at 450 °C. Even when the temperature is as low as 200 °C, there is still an output power of 3 mW. Stability of the cell under 600 °C is tested by operating the cell at a constant voltage of 0.7 V. The test lasts for 30 h during which the operating power density decreases rapidly in the first 10 h, then tend to be stable at 300 mW cm−2. [ABSTRACT FROM AUTHOR]

Seven tacrine/ CHR21 conjugates have been designed and synthesized. Compound 8-7 was confirmed as the most active AChE inhibitor with IC 50 value of 5.8 ± 1.4 nM, which was 7.72-fold stronger than tacrine. It was also shown as a strong BuChE inhibitor (IC 50 value of 3.7 ± 1.3 nM). 8-7 was clearly highlighted not only as an excellent ChEs inhibitor, but also as a good modulator on protein expression of AChE, p53, Bax, Bcl-2, LC3, p62, and ULK, indicating its functions against programmed cell apoptosis and decrease of autophagy. 8-7 significantly reversed the glutamate-induced dysfunctions including excessive calcium influx and release from internal organelles, overproduction of nitric oxide (NO) and Aβ high molecular weight oligomer. This compound can penetrate blood−brain barrier (BBB). The in vivo hepatotoxicity assay indicated that 8-7 was much less toxic than tacrine. Altogether, these data strongly support that 8-7 is a potential multitarget-directed ligand (MTDL) for treating Alzheimer's disease (AD). Image 1 • 8-7 was a stronger AChE and BuChE inhibitor than tacrine. • 8-7 was a better modulator on programmed cell apoptosis than tacrine. • 8-7 was able to modulate cell autophagy, while tacrine could not. • 8-7 showed much less hepatotoxicity than tacrine. [ABSTRACT FROM AUTHOR]

• Phosphorylation of RssB happens on the interface thus weakens the interaction σS. • IraD interacts with the RssB at higher affinity regardless of phosphorylation. • A new two-tier mechanism for controlled proteolysis of σS is proposed. RssB is fully activated during logarithmic growth, promoting σS degradation. Phosphorylation on D58 partially switches the degradation off as the phosphorylation reduces RssB affinity for σS. The binding of anti-adaptor protein IraD to RssB prevents any RssB- σS interaction and shuts off σS degradation completely. Regulation of bacterial stress responding σS is a sophisticated process and mediated by multiple interacting partners. Controlled proteolysis of σS is regulated by RssB which maintains minimal level of σS during exponential growth but then elevates σS level while facing stresses. Bacteria developed different strategies to regulate activity of RssB, including phosphorylation of itself and production of anti-adaptors. However, the function of phosphorylation is controversial and the mechanism of anti-adaptors preventing RssB-σS interaction remains elusive. Here, we demonstrated the impact of phosphorylation on the activity of RssB and built the RssB-σS complex model. Importantly, we showed that the phosphorylation site - D58 is at the interface of RssB-σS complex. Hence, mutation or phosphorylation of D58 would weaken the interaction of RssB with σS. We found that the anti-adaptor protein IraD has higher affinity than σS to RssB and its binding interface on RssB overlaps with that for σS. And IraD-RssB complex is preferred over RssB-σS in solution, regardless of the phosphorylation state of RssB. Our study suggests that RssB possesses a two-tier mechanism for regulating σS. First, phosphorylation of RssB provides a moderate and reversible tempering of its activity, followed by a specific and robust inhibition via the anti-adaptor interaction. [ABSTRACT FROM AUTHOR]

• Fluid elasticity deforms CO 2 bubbles into elongated bubbles with cusp-like trailing ends. • Dissolution of CO 2 bubbles in polyacrylamide aqueous solutions leads to progressive decrease in rise velocity. • The presence of polymer drastically reduces the mass transfer in water due to low bubble velocity and high bubble contamination. • Mobile gas–liquid interface prevails in tap water, while bubbles behave as rigid particles in polyacrylamide aqueous solutions. Single CO 2 bubbles rising in quiescent viscoelastic polyacrylamide (PAA) aqueous solutions of different weight percentages (wt. %) were studied to obtain insight into the impact of fluid elasticity on the rising dynamics of dissolving bubbles. A random abrupt fall and rise in velocity was observed as the bubble velocity gradually and progressively decreased throughout the journey. This is the first time this observation is reported. In the most viscoelastic medium in which this phenomenon occurred, CO 2 bubbles decreased in diameter by at least 20% over 1m of height. Mass transfer analysis of the system indicated significant reduction of mass transfer coefficient with increase in weight percentage of the polymer solution. Comparison of experimental mass transfer coefficients with predictions for mobile and immobile gas-liquid interfaces were consistent with theoretical predictions from Higbie's and Frössling's equations respectively. The rising dynamics was correlated using dimensional analysis, and the prediction by a developed empirical correlation considering the combined effect of fluid elasticity and shear-thinning property showed a satisfactory agreement with experimental data in all liquids studied. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

A mechanically rechargeable direct carbon fuel cell stack, with 12 cells electrically connected in series on a single YSZ electrolyte plate, can directly use carbon-rich fuels to generate electrical power of over 10 W at 800 °C, revealing a specific energy of 2000 Wh kg−1. • A 12-cell-stack of direct carbon fuel cell is made on a single electrolyte plate. • The stack is mechanically rechargeable. • Output power of the stack using Fe-loaded activated carbon is over 10 W at 800 °C. • Specific energy of the 12-cell-stack can reach 2000 Wh kg−1. • A stack directly using sawdust of tree branch outputs a power of 13.1 W at 800 °C. The direct carbon solid oxide fuel cell is a potential technology that efficiently and cleanly converts the chemical energy of solid carbon into electricity. Its superiority of all-solid-state configuration and unique operating mechanism indicate that it has a good application prospect in high energy density portable or backup power supplys. It can also be used to convert coal into electrical power. Here, for the first time, we report a compact direct carbon solid oxide fuel cell stack with 12 cells fabricated on a single 10 × 10 cm electrolyte plate. The plate covers a container filled with solid carbon-rich fuel to form a stack. No sealant and pipelines are needed and the carbon-rich fuel can be reloaded. Both activated carbon and sawdust of bauhinia tree branch are used as the fuel. The output power of such a stack approaches more than 10 W at 800 °C. Using 15 g of 5 wt% Fe-loaded activated carbon as the fuel, a stack discharging at a constant current of 1.5 A outputs an energy of 29 Wh, correspongding to an energy desnity of carbon of ∼2000 Wh kg−1. This work shows the feasibility of developing direct carbon solid oxide fuel cell into a compact electricity generator using readily available carbon-rich fuels. It also shows promise of using this technology in clean and efficient conversion of coal to electricity. [ABSTRACT FROM AUTHOR]

• An electrochemiluminescent biosensor based on Au@CDs for detection of CTCs is described. • The prepared Au@CDs possess significant enhanced electrochemiluminescence emission. • The proposed method was sensitive, separation-free and label-free strategy. In this work, new gold@carbon dots nanoalloys (Au@CDs) were synthesized by directly heating carbon dots (CDs) and HAuCl 4 aqueous solution to boiling. The as-synthesized Au@CDs exhibited 12-fold enhancement in the ECL emission compared to the single CDs. The high luminous efficiency Au@CDs was further used to fabricate an ECL cytosensor for the direct detection of circulating tumor cells (CTCs) in serum by ligation of a cell-specific aptamer. Briefly, human mucin1 protein (MUC1) aptamer was immobilized onto the surface of Au@CDs on the electrode for capturing MUC1-positive MCF-7 cells (a type of CTCs). On the basis of the increased steric hindrance, the captured MCF-7 cells can be quantitatively detected. Our strategy was free from complicated separation and labeling treatment, and realized the detection of MCF-7 cells (a type of CTCs) from 100 to 10,000 cells/mL with a detection limit of 34 cells/mL, offering promising applications in ultrasensitive routine clinical analysis and point-of-care testing. [ABSTRACT FROM AUTHOR]

Through the bursting of microbubbles prepared by a T-junction microfluidic device with uniform particle size, bio-inspired alginate nanoparticles were obtained via shell disintegration process. The high-speed microscopy and digital image technology were used to observe the evolution of the microbubble raft before bubble bursting. To investigate the mechanism of nanoparticle formation, a theoretical approach combining the shell disintegration theory and the rule of the ligament breakup was developed through which the size of nanoparticles could be predicted. Such analysis showed that the bubble size and the viscosity of the alginate solution to generate bubbles were both key factors for determining the average particle size and size distribution and such results were proved experimentally. Also, the size distribution of the nanoparticles were found to be very well represented by gamma distributions , underlying the crucial role played by the ligament dynamics in building up the broad statistics of sprays. [ABSTRACT FROM AUTHOR]

Natural rubusoside (RUB) efficiently encapsulates NBD C6-Ceramide, a short chain ceramide to form RUB-assisted nanomicelles (∼29 nm) in aqueous solution. This novel nanomicelles can make water insoluble NBD C6-Ceramide bioavailable in vivo following drug administration, especially by intravenous administration for cancer treatments. • A novel rubusoside-assisted solubilization system for NBD C 6 -Ceramide was developed to efficiently enhance its solubility. • This new solubilization system can be easily delivered in vivo and applied for a pilot pharmacokinetic study. • This technique is a great option to enhance solubility for lipophilic molecules besides organic solvents and surfactants. Although C 6 -Ceramide has attracted much attention as a possible tumor suppressor, the delivery of C 6 -Ceramide is still challenging due to its inherent hydrophobicity and insolubility. In this study we explored the use of a natural compound rubusoside (RUB) as a solubilizer to enhance the solubility of a fluorescence-labeled C 6 -Ceramide (NBD C 6 -Ceramide) and to characterize its pharmacokinetics and tissue distribution in an animal model. RUB significantly enhanced the solubility of NBD C 6 -Ceramide by forming nanomicelles, and efficiently delivered NBD C 6 -Ceramide in rats by oral and intravenous administration. RUB loaded 1.96 % of NBD C 6 -Ceramide in the nanomicelles and solubilized it to a concentration of 3.6 mg/mL in water. NBD C 6 -Ceramide in nanomicelles remained stable in aqueous solutions, allowing intravenous administration without the use of any organic solvents or surfactants. After oral administration, NBD C 6 -Ceramide rapidly rose to peak plasma concentrations within the first 90 min, distributed to tissues, and remained in vivo for more than 24 h. Tissular levels of NBD C 6 -Ceramide from high to low were associated with heart, lung, cerebellum, testicle, spleen, liver, kidney, and brain. Altogether, our study demonstrated that RUB-assisted nanomicelles can serve as an efficient and convenient delivery system for short-chain C 6 -Ceramide and enable in vivo evaluation of potential new cancer treatments. [ABSTRACT FROM AUTHOR]

The phase transformation and precipitation mechanism of Nb microalloyed offshore platform steel during continuous cooling are studied by the thermal expansion method and transmission electron microscopy. The results show that a large amount of NbC is precipitated in the investigated steel during phase transformation and is classified into three types according to its size: Type I (>100 nm) is randomly generated in the austenitization stage; type II (20–100 nm) is precipitated by stress induction during thermal deformation; and type III (≈10 nm) is formed by the combination of segregated C and Nb during the cooling process after the formation of bainitic ferrite matrix. In addition, herein, a model of phase transition and precipitation behavior at different cooling rates is designed. At a low cooling rate (0.5 °C s−1), the microstructure consists of a granular structure formed by diffusion and granular bainite formed by shearing, which is a diffusion phase transformation. At a medium cooling rate (3 °C s−1), the orientation relationship of ferrite and austenite is [001]α//[011]γ and (110)α//(−1−11)γ, which is semidiffusion and a half‐shear mechanism. At a high cooling rate (15 °C s−1), there are a large number of intertwined dislocations in martensite, which is a shear mechanism. [ABSTRACT FROM AUTHOR]

NDM-1-producing Enterobacteriaceae are multidrug-resistant bacteria, also called superbacteria, that have become important global human health threats in recent years. However, data about NDM-1-producing bacteria in animals are rare. In this study, an NDM-1-producing Escherichia coli isolate (designated E120413) was obtained from pigs in Henan province, China in 2012. The susceptibility of E. coli E120413 to antimicrobial agents was determined using Kirby-Bauer disk diffusion and micro-dilution methods. Susceptibility tests indicated that E. coli E120413 was resistant to almost all common antibiotics with high MIC values obtained for most antibiotics tested. E. coli E120413 was detected in the heart, liver, spleen, lung, kidney, brain, stomach, duodenum, mesenteric lymph nodes, and fecal samples of piglets in both cohabitation and experimental groups and the bacteria persisted for more than 2 weeks. However, no obvious clinical symptoms or serious pathological lesions were observed. This is the first investigation of NDM-1-producing E. coli isolate from pigs in China. Although no significant pathological lesions were observed, NDM-1-producing E. coli was found to be highly transmissible and to cause persistent infection in pigs. • First investigation of NDM-1-producing E. coli isolate from pigs in China. • NDM-1-producing E. coli persisted for more than 2 weeks in piglets. • No significant pathological lesions were observed in piglets infected with NDM-1-producing E. coli. [ABSTRACT FROM AUTHOR]

Summary Receptor clustering on the cell membrane is critical in the signaling of many immunoreceptors, and this mechanism has previously been attributed to the extracellular and/or the intracellular interactions. Here, we report an unexpected finding that for death receptor 5 (DR5), a receptor in the tumor necrosis factor receptor superfamily, the transmembrane helix (TMH) alone in the receptor directly assembles a higher-order structure to drive signaling and that this structure is inhibited by the unliganded ectodomain. Nuclear magnetic resonance structure of the TMH in bicelles shows distinct trimerization and dimerization faces, allowing formation of dimer-trimer interaction networks. Single-TMH mutations that disrupt either trimerization or dimerization abolish ligand-induced receptor activation. Surprisingly, proteolytic removal of the DR5 ectodomain can fully activate downstream signaling in the absence of ligand. Our data suggest a receptor activation mechanism in which binding of ligand or antibodies to overcome the pre-ligand autoinhibition allows TMH clustering and thus signaling. Graphical Abstract Highlights • Transmembrane helix of death receptor 5 oligomerizes to drive downstream signaling • The transmembrane helix in lipid bilayer forms dimer-trimer interaction network • Receptor ectodomain in pre-ligand state inhibits receptor clustering and activation • Ligand binding overcomes the pre-ligand autoinhibition Unlike traditional receptor clustering mediated by intracellular and extracellular domain oligomerization, the transmembrane domain alone of some TNF family receptors can form higher-order structures competent to drive signaling, basally inhibited by the unliganded ectodomain. [ABSTRACT FROM AUTHOR]

Epidemiological data from the Center of Disease Control (CDC) and the World Health Organization (WHO) statistics in 2017 show that 10.0 million people around the world became sick with tuberculosis. Mycobacterium tuberculosis (MTB) is an intracellular parasite that mainly attacks macrophages and inhibits their apoptosis. It can become a long-term infection in humans, causing a series of pathological changes and clinical manifestations. In this review, we summarize innate immunity including the inhibition of antioxidants, the maturation and acidification of phagolysosomes and especially the apoptosis and autophagy of macrophages. Besides, we also elaborate on the adaptive immune response and the formation of granulomas. A thorough understanding of these escape mechanisms is of major importance for the prevention, diagnosis and treatment of tuberculosis. [ABSTRACT FROM AUTHOR]

The intrinsically disordered protein, Tau, is abundant in neurons and contributes to the regulation of the microtubule (MT) and actin network, while its intracellular abnormal aggregation is closely associated with Alzheimer's disease. Here, using in-cell Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated the conformations of two different isoforms of Tau, Tau40 and k19, in mammalian cells. Combined with immunofluorescence imaging and western blot analyses, we found that the isotope-enriched Tau, which was delivered into the cultured mammalian cells by electroporation, is partially colocalized with MT and actin filaments (F-actin). We acquired the NMR spectrum of Tau in human embryonic kidney 293 (HEK-293T) cells, and compared it with the NMR spectra of Tau added with MT, F-actin, and a variety of crowding agents, respectively. We found that the NMR spectrum of Tau in complex with MT best recapitulates the in-cell NMR spectrum of Tau, suggesting that Tau predominantly binds to MT at its MT-binding repeats in HEK-293T cells. Moreover, we found that disease-associated phosphorylation of Tau was immediately eliminated once phosphorylated Tau was delivered into HEK-293T cells, implying a potential cellular protection mechanism under stressful conditions. Collectively, the results of our study reveal that Tau utilizes its MT-binding repeats to bind MT in mammalian cells and highlight the potential of using in-cell NMR to study protein structures at the residue level in mammalian cells. [ABSTRACT FROM AUTHOR]

Summary The mitochondrial uncoupling protein 1 (UCP1) generates heat by causing proton leak across the mitochondrial inner membrane that requires fatty acid (FA). The mechanism by which UCP1 uses FA to conduct proton remains unsolved, and it is also unclear whether a direct physical interaction between UCP1 and FA exists. Here, we have shown using nuclear magnetic resonance that FA can directly bind UCP1 at a helix-helix interface site composed of residues from the transmembrane helices H1 and H6. According to the paramagnetic relaxation enhancement data and molecular dynamics simulation, the FA acyl chain appears to fit into the groove between H1 and H6 while the FA carboxylate group interacts with the basic residues near the matrix side of UCP1. Functional mutagenesis showed that mutating the observed FA binding site severely reduced UCP1-mediated proton flux. Our study identifies a functionally important FA-UCP1 interaction that is potentially useful for mechanistic understanding of UCP1-mediated thermogenesis. [ABSTRACT FROM AUTHOR]