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A thermal multiphase lattice Boltzmann (LB) model is used to study the behavior of droplet impact on hot surface and the relevant heat transfer properties. After validating the correctness of the codes through the D2 law, the simulations of intrinsic contact angle and the temperature-dependent surface tension are performed. The LB model is then used to simulate the droplet impact on smooth and micro-hole heated surface. On the smooth surface, the impinging droplet is reluctant to rebound, unless the intrinsic wettability of the solid surface is fairly good. On the micro-hole surface, however, the micro-holes provide favorable sites for generating a high-pressure vapor cushion underneath the impinging droplet, which thereby facilitates the continuous droplet rebound. For the continuously rebounding droplet. The time evolution of volume and temperature display obvious oscillations. The achievable height of the rebounding droplet increases as the intrinsic wettability of the solid surface becomes better, and the maximum transient heat flux is found to be directly proportional to the droplet rebounding height. Within a certain time interval, the continuous rebounding behavior of the droplet is favorable for enhancing the total heat quantity/heat transfer efficiency, and the influence of intrinsic wettability on the total heat during droplet impingement is greater than that of the superheat. The LB simulations not only present different states of droplets on hot surfaces, but also guide the design of the micro-hole surface with desirable heat transfer properties. [ABSTRACT FROM AUTHOR]

Previous studies have established that cytochrome P450 enzymes (CYPs) in both liver and lung are capable of bioactivating naphthalene (NA), an omnipresent air pollutant and possible human carcinogen, in vitro and in vivo. The aim of this study was to examine the specific contribution of pulmonary CYPs in airway epithelial cells to NA-induced airway toxicity. We used a lung- Cpr -null mouse model, which undergoes doxycycline-induced, Cre-mediated deletion of the Cpr (a redox partner of all microsomal CYPs) gene specifically in airway epithelial cells. In 2-month-old lung- Cpr -null mice, Cpr deletion occurred in 75%–82% of epithelial cells of conducting airways. The extent of NA-induced acute lung toxicity (as indicated by total protein concentration and lactate dehydrogenase activity in bronchoalveolar lavage fluid collected at 24-h after initiation of a 4-h, nose-only, 10-ppm NA inhalation exposure) was substantially lower (by 37%–39%) in lung- Cpr -null mice, compared with control littermates. Moreover, the extent of cellular proliferation (as indicated by 5-bromo-2′-deoxyuridine incorporation) was noticeably lower in both proximal and distal airways (by 59% and 65%, respectively) of NA-treated lung- Cpr -null mice, compared with control littermates, at 2-day post-NA inhalation exposure. A similar genotype-related difference in the extent of postexposure cell proliferation was also observed in mice exposed to NA via intraperitoneal injection at 200 mg/kg. These results directly validate the hypothesis that microsomal CYP enzymes in airway epithelial cells play a large role in causing injury to airway epithelia following exposure to NA via either inhalation or intraperitoneal route. [ABSTRACT FROM AUTHOR]

Many constituents of tobacco smoke (TS) require bioactivation to exert toxic effects; however, few studies have examined the role of bioactivation enzymes in the adverse effects of TS exposure. This knowledge gap is a major source of uncertainty for risk assessment and chemoprevention efforts. Our aim is to test the hypothesis that cytochrome P450 (P450) enzyme-mediated bioactivation is essential to the development of TS exposure-induced lung toxicity, by determining the contributions of P450 enzymes in the mouse Cyp2abfgs gene subfamilies to environmental tobacco smoke (ETS)-induced lung inflammation. Adult female wildtype (WT) and Cyp2abfgs -null mice (both on C57BL/6J background) were exposed to filtered air or ETS, intermittently, for 1 or 2 weeks. Lung inflammation was assessed by quantification of inflammatory cells, cytokines, chemokines, and proteins in bronchoalveolar lavage fluid (BALF) and histopathological analysis. Glutathione (GSH) conjugates of 2 ETS constituents, naphthalene (NA), and 3-methylindole (3MI), were measured in mice exposed to ETS for 4 h. Persistent macrophagic and neutrophilic lung inflammation was observed in ETS-exposed WT mice; the extent of which was significantly reduced in ETS-exposed Cyp2abfgs -null mice. Levels of proinflammatory cytokines and chemokines, along with the total protein concentration, were increased in cell-free BALF from ETS-exposed WT mice, but not Cyp2abfgs -null mice. Additionally, GSH conjugates of NA and 3MI were detected in the lungs of WT, but not Cyp2abfgs -null, mice following ETS exposure. These results provide the first in vivo evidence that the mouse Cyp2abfgs gene cluster plays an important role in ETS-induced lung inflammation. [ABSTRACT FROM AUTHOR]

• Nano-texturized NiO (0 0 1) films were epitaxially grown on MgO (0 0 1) substrates. • Morphology evolution and the influence of deposition conditions were studied. • Formation mechanism of nano-texturized structure was discussed. • Optical properties of the Nano-texturized NiO films were determined. Epitaxial films with nanostructures are of great significance for some special applications. In this work, nano-texturized NiO films are epitaxially grown on MgO (0 0 1) substrates by a reactive magnetron sputtering method. The evolution in morphology is studied as a function of deposition time, and the influences of substrate temperature, oxygen partial pressure, and the substrate treatment before deposition of NiO on the formation of nano-texturized NiO films are explored. It is found that the non-symmetrically epitaxial growth of nano-texturized NiO films can be linked with the surface damages of MgO (0 0 1) substrate, which leads to the coalescence of adjacent NiO grains preferentially occurs along the direction of 〈100〉 and 〈010〉, but they do not coalesce simultaneously following the other directions. In addition, the optical property of nano-texturized NiO films is studied using the Cauchy model. [ABSTRACT FROM AUTHOR]

Molybdenum phosphide nanoparticles loaded with mesoporous carbon was facile prepared by dual-step pyrolysis of MOF template. Due to its mesoporous structure, large specific surface area, high conductivity, and good catalytic activity, the composite showed enhanced electrochemical sensing performance for acetaminophen detection. [Display omitted] • MoP loaded with mesoporous carbon was prepared by dual-step pyrolysis method. • MoP nanoparticles were uniformly dispersed in the mesoporous carbon matrix. • MoP@C-D2@GCE showed excellent performance for acetaminophen sensing. • MoP@C-D2@GCE can be used to detect acetaminophen in commercial medicine. Electrochemical methods have attracted great attention in the detection of acetaminophen (AP) due to their high sensitivity, rapidity, and simplicity. Molybdenum phosphide (MoP) with excellent catalytic activity and redox property has been widely used for electrochemical applications. In this work, MoP nanoparticles loaded with mesoporous carbon (MoP@C-D2) were successfully synthesized and characterized by powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) method, and X-ray photoelectron spectroscopy (XPS). It is shown that the temperature rising process and the amount of polyoxometalate and NaH 2 PO 2 can significantly affect the specific surface areas and pore structures of the product, thereby affecting their sensing performances. Structural studies indicated that MoP nanoparticles in MoP@C-D2 were uniformly dispersed in mesoporous carbon matrix, endowing the composite high conductivity, large specific surface area, and good catalytic activity. MoP@C-D2 modified electrode showed a wide linear detection range of 1.24–1071.4 μM, the detection of limit (LOD) of 0.008 μM, high stability, and good selectivity for AP detection. In addition, the constructed electrode can also be used to detect the content of AP in commercial medicine. This work extends the application of mesoporous MoP-based composite in electrochemical sensing. [ABSTRACT FROM AUTHOR]

Abstract: Fructose is a nutritional composition of fruits and honey. Its excess consumption induces insulin resistance-associated metabolic diseases. Hypothalamic insulin signaling plays a pivotal role in controlling whole-body insulin sensitivity and energy homeostasis. Quercetin, a natural flavonoid, has been reported to ameliorate high fructose-induced rat insulin resistance and hyperlipidemia. In this study, we investigated its regulatory effects on the hypothalamus of high fructose-fed rats. Rats were fed 10% fructose in drinking water for 10 weeks. After 4 weeks, these animals were orally treated with quercetin (50 and 100 mg/kg), allopurinol (5 mg/kg) and water daily for the next 6 weeks, respectively. Quercetin effectively restored high fructose-induced hypothalamic insulin signaling defect by up-regulating the phosphorylation of insulin receptor and protein kinase B. Furthermore, quercetin was found to reduce metabolic nutrient sensors adenosine monophosphate-activated protein kinase (AMPK) activation and thioredoxin-interacting protein (TXNIP) overexpression, as well as the glutamine–glutamate cycle dysfunction in the hypothalamus of high fructose-fed rats. Subsequently, it ameliorated high fructose-caused hypothalamic inflammatory lesions in rats by suppressing the activation of hypothalamic nuclear factor κB (NF-κB) pathway and NOD-like receptor 3 (NLRP3) inflammasome with interleukin 1β maturation. Allopurinol had similar effects. These results provide in vivo evidence that quercetin-mediated down-regulation of AMPK/TXNIP and subsequent inhibition of NF-κB pathway/NLRP3 inflammasome activation in the hypothalamus of rats may be associated with the reduction of hypothalamic inflammatory lesions, contributing to the improvement of hypothalamic insulin signaling defect in this model. Thus, quercetin with the central activity may be a therapeutic for high fructose-induced insulin resistance and hyperlipidemia in humans. [Copyright &y& Elsevier]

Abstract: Anthracnose caused by Colletotrichum spp. is one of the most destructive diseases of cultivated strawberry (Fragaria × ananassa Duchesne) worldwide. The correlation between NBS–LRR genes, the largest class of known resistance genes, and strawberry anthracnose resistance has been elusive. BLAST search in NCBI identified 94 FvNBSs in the diploid genome of strawberry Fragaria vesca, with 67 of the TIR–NBS–LRR type. At least 36 FvNBSs were expressed, with 25% being non-coding genes. Two F. vesca ecotypes, HLJ and YW, showed great variations in both morphological and physiological responses upon C. gloeosporioides infection. qRT-PCR revealed that 5 of the 12 leaf-expressed FvNBSs displaying opposite transcription responses to C. gloeosporioides infection in two ecotypes. These results showed that the transcriptional responses of several FvNBSs were involved in the ecotype-specific responses to C. gloeosporioides in F. vesca. These FvNBSs hold potential in characterizing molecular components and developing novel markers associated with anthracnose resistance in strawberry. [Copyright &y& Elsevier]

Abstract: Compared with control rats, rats under morphine exposure exhibited cannabinoid receptor 2 (CB2-R) upregulation in the spleen and periphery blood mononuclear cells (PBMCs). IgG and IgM values in the plasma were also altered. In morphine abusers, cannabinoid receptors were upregulated in the PBMCs, and the expression of IL-4 mRNA in the PBMCs as well as the IgG and IgM values in the plasma were higher compared with those in healthy people. The expression of cannabinoid receptor 1 and CB2-R in culture cells was directly affected by morphine treatment. These findings indicate that the alteration in cannabinoid receptor expression could be disturbed by morphine exposure, and it may be involved in abnormal immune function. [Copyright &y& Elsevier]

Abstract: International Vehicle Emissions (IVE) model funded by U.S. Environmental Protection Agency (USEPA) is designed to estimate emissions from motor vehicles in developing countries. In this study, the IVE model was evaluated by utilizing a dataset available from the remote sensing measurements on a large number of vehicles at five different sites in Hangzhou, China, in 2004 and 2005. Average fuel-based emission factors derived from the remote sensing measurements were compared with corresponding emission factors derived from IVE calculations for urban, hot stabilized condition. The results show a good agreement between the two methods for gasoline passenger cars'' HC emission for all IVE subsectors and technology classes. In the case of CO emissions, the modeled results were reasonably good, although systematically underestimate the emissions by almost 12%-50% for different technology classes. However, the model totally overestimated NOA emissions. The IVE NOA emission factors were 1.5-3.5 times of the remote sensing measured ones. The IVE model was also evaluated for light duty gasoline truck, heavy duty gasoline vehicles and motor cycles. A notable result was observed that the decrease in emissions from technology class State II to State I were overestimated by the IVE model compared to remote sensing measurements for all the three pollutants. Finally, in order to improve emission estimation, the adjusted base emission factors from local studies are strongly recommended to be used in the IVE model. [Copyright &y& Elsevier]

Abstract: The aim of this study was to prepare and characterize a transgenic mouse model in which CYP2A6, a human P450 enzyme, is expressed specifically in the liver. CYP2A6, which is mainly expressed in human liver, is active toward many xenobiotics. Our transgene construct contained the mouse transthyretin promoter/enhancer, a full-length CYP2A6 cDNA, and a downstream neomycin-resistance gene for positive selection in embryonic stem cells. Hepatic expression of the CYP2A6 transgene was demonstrated by immunoblotting, whereas tissue specificity of CYP2A6 expression was confirmed by RNA-PCR. The transgenic mouse was further characterized after being backcrossed to the B6 strain for six generations. Hepatic microsomes from homozygous transgenic mice had activities significantly higher than those of B6 mice toward coumarin. The in vivo activity of transgenic CYP2A6 was also determined. Systemic clearance of coumarin was significantly higher in the transgenic mice than in B6 controls, consistent with the predicted role of CYP2A6 as the major coumarin hydroxylase in human liver. The CYP2A6-transgenic mouse model should be valuable for studying the in vivo function of this polymorphic human enzyme in drug metabolism and chemical toxicity. [Copyright &y& Elsevier]

The optical properties of semispherical Ag-SiO2 nanocaps (Ag-SiO2-NCs) with Ag layers thinner than 20 nm are studied by a method of finite-difference time-domain (FDTD) simulations. The Ag-SiO2-NCs exhibit the enhanced extinction basically appearing in infrared band and the plasmon resonance can be almost linearly tuned to any given wavelength by changing the SiO2 radius. With the decrease in the thickness of Ag layers from 20 to 4 nm, the Ag-SiO2-NCs enable the local electric fields to be extremely enhanced as high as more than three orders of magnitude and to be extended into the substrate region deep to ~ 50 nm, exhibiting a great potential in the applications of enhancing infrared fluorescence. Due to the coupling of localized plasmons, the local electric fields in the gap regions between two Ag-SiO2-NCs will be further enhanced, about one order of magnitude higher than those enhanced by pure Ag nanoparticles with the same sizes. [ABSTRACT FROM AUTHOR]

Aging increases susceptibility to lung disease, but the topic is understudied, especially in relation to environmental exposures with the bulk of rodent studies using young adults. This study aims to define the pulmonary toxicity of naphthalene (NA) and the impacts of a dietary antioxidant, ergothioneine (ET), in the liver and lungs of middle-aged mice. NA causes a well-characterized pattern of conducting airway epithelial injury in the lung in young adult mice, but NA's toxicity has not been characterized in middle-aged mice, aged 1–1.5 years. ET is a dietary antioxidant that is synthesized by bacteria and fungi. The ET transporter (ETT), SLC22A4, is upregulated in tissues that experience high levels of oxidative stress. In this study, middle-aged male and female C57BL/6 J mice, maintained on an ET-free synthetic diet from conception, were gavaged with 70 mg/kg of ET for five consecutive days. On day 8, the mice were exposed to a single intraperitoneal NA dose of 50, 100, 150, or 200 mg/kg. At 24 hours post NA injection samples were collected and analyzed for ET concentration and reduced (GSH) and oxidized glutathione (GSSG) concentrations. Histopathology, morphometry, and gene expression were examined. Histopathology of mice exposed to 100 mg/kg of NA suggests reduction in toxicity in the terminal airways of both male (p ≤ 0.001) and female (p ≤ 0.05) middle-aged mice by the ET pretreatment. Our findings in this study are the first to document the toxicity of NA in middle-aged mice and show some efficacy of ET in reducing NA toxicity. • Differential expression of Phase 2 associated genes were measured by lung location. • Microdissection allowed study of lung location naphthalene dose effects by sex. • Naphthalene pulmonary toxicity was measured in middle-aged mice for the first time. • Oral ergothioneine pretreatment led to modest reductions in naphthalene toxicity. [ABSTRACT FROM AUTHOR]

The optical properties of nanostructures are rather important for designing plasmonic devices. In this work, the plasmonic properties of Ag-coated spherical dielectric nanoparticles (NPs), namely, Ag-SiO2-NPs, Ag-ZnO-NPs, and Ag-TiO2-NPs, were studied using a method of finite-difference time-domain calculations. It was found that the Ag-coated dielectric NPs start to exhibit unique plasmonic properties different from Ag-NPs as the thickness of Ag shells is reduced to be less than a critical value, which is basically determined by the penetration depth of light in silver. On the other hand, the core–shell structures of Ag-coated dielectric NPs were found to be of benefit to the plasmonic resonance high-efficiently coupled with the incident light. In the extinction spectra of Ag-coated dielectric NPs with sufficient thin Ag shells, the dipole plasmonic resonance is predominant and exhibits a pronounced red-shift up to infrared band with increasing the NP sizes. In addition to the electromagnetic waves of emission towards the outside, the electromagnetic field in the dielectric NP inside is uniformly enhanced as well and both of dipole and quadrupole plasmonic resonances are identified. The Ag-coated dielectric NPs are suggested to have great potential in the plasmonic devices working in infrared band, such as the light emitters and SERS substrates for biosensing. [ABSTRACT FROM AUTHOR]

A diamond film was deposited using a two-step process in which nitrogen is added during the second step. We compare the defects in {001} and {111} growth sectors from the two-steps: dislocation loops found in {001} growth sectors of the first step disappear in {001} growth sectors with N-doping, whereas the density of planar defects in {111} growth sectors strongly increases. It is suggested that N-doping stops vacancies from aggregating to form dislocation loops or vacancy clusters. [Copyright &y& Elsevier]

The origin of green luminescence (GL) band is an issue long‐term pending in the research of ZnO. Herein, three GL bands (GL1, GL2, and GL‐S bands) are unambiguously identified using the single‐crystal samples with and without a SiOx passivation layer and the polycrystal samples annealed in H2 and O2 atmospheres. Solid evidence demonstrates that the GL1 band can be assigned to the optical emissions from the sample inside and the intensity is decreased with the decrease in temperature. The GL2 and GL‐S bands, which correspond to the structureless and structured GL bands of H‐ and O‐annealed samples, respectively, are found to come from the sample surface and enhanced at low temperatures. Excitons or free electrons and holes generated through interband absorption are found to play an important role in exciting both the GL2 and GL‐S bands. For the light with photon energy lower than the bandgap, however, the GL‐S and GL2 bands exhibit different excitation behaviors. The deficiency of oxygen on the sample surface is confirmed to be the reason resulting in the GL2 band and probably also the reason leading to the GL‐S band. [ABSTRACT FROM AUTHOR]

Objectives: Oligo-/polysaccharides from Cyathula officinalis Kuan (COPs) and Achyranthes bidentata Blume (ABPs) have attracted researchers' attention in the fields of healthy food supplements and traditional Chinese medicine (Niúxī) due to their multiple bioactivities combined with their nontoxic and highly biocompatible nature. The purpose of this paper was to provide a systematic and comprehensive overview of the extraction, purification, and structural analysis methods, chemical characteristics, biological activities, and structure bioactivity relationship. Furthermore, the possible development trends and perspectives for future research, and traditional uses of Niúxī are also summarized. Methods: All the information was gathered from a library search and scientific databases. Key findings: Although COPs and ABPs are derived from different plants, they have similar structural features in type, structure, and glycosidic linkage patterns and biological activities in vivo and in vitro. However, there are differences in monosaccharide compositions, which can be used as an identification mark. Conclusions: As traditional Chinese herbal medicine, C. officinalis and A. bidentata have similar pharmacological activities. The COPs and ABP possess wide pharmacological effects such as antitumor, antioxidant, anti-osteoporosis, and anti-inflammatory. Meanwhile, the biological activity and structure–activity relationship of purified COPs and ABPs are less studied, future research should focus on them. Graphical Abstract [ABSTRACT FROM AUTHOR]

• A mathematical model of rolling force imbedding the deformation penetration coefficient is established. • The rolling force is positive correlation with the deformation penetration coefficient and the roller velocity. • The larger the reduction and the ratio of the plate thickness to diameter are, the bigger the required rolling force are. The deformation characteristic of an ultra-heavy plate in thickness direction is described by introducing a parameter, called deformation penetration coefficient, and the rolling force model taking this parameter into account in the broadside stage is established. In this paper, the deformation penetration coefficient is defined as the ratio of the actual deformation depth to the overall plate thickness, which is shown as the function of the initial thickness, the pass reduction and the critical shape factor. Since the plate width speard can be neglected during broadside rolling, a two-dimensional velocity field is constructed by simplifying a classical three-dimensional velocity field. For the purpose of solving the problem of functional integration originated from the nonlinear Mises specific plastic power, the simplified velocity field is analyzed by the geometric approximation (GA) yield criterion, and the internal deformation power is obtained. Moreover, the friction power and the shear power are obtained by the inner product method of the strain vector and the mean velocity intergral method, respectively. The analytical solution of rolling force is obtained by the variational method, and its value for each pass is compared with the measured data from a domestic factory. The comparison result shows that the rolling force model in this paper has a high predictive accuracy, since the maximum error is less than 8.6%. The rolling parameter analysis shows that the deformation penetration coefficient, the pass reduction and the ratio of plate thickness to diameter affect the rolling force of the ultra-heavy plate apparently. [ABSTRACT FROM AUTHOR]

A cellular automaton-lattice Boltzmann coupled model is extended to study the dendritic growth with melt convection in the solidification of ternary alloys. With a CALPHAD-based phase equilibrium engine, the effects of melt convection, solutal diffusion, interface curvature and preferred growth orientation are incorporated into the coupled model. After model validation, the multi dendritic growth of the Al-4.0 wt%Cu-1.0 wt%Mg alloy is simulated under the conditions of pure diffusion and melt convection. The result shows that the dendritic growth behavior, the final microstructure and microsegregation are significantly influenced by melt convection in the solidification. [ABSTRACT FROM AUTHOR]

We determined whether a decrease in hepatic microsomal cytochrome P450 activity would impact lung toxicity induced by inhalation exposure to naphthalene (NA), a ubiquitous environmental pollutant. The liver-Cpr-null (LCN) mouse showed decreases in microsomal metabolism of NA in liver, but not lung, compared to wild-type (WT) mouse. Plasma levels of NA and NA-glutathione conjugates (NA-GSH) were both higher in LCN than in WT mice after a 4-h nose-only NA inhalation exposure at 10 ppm. Levels of NA were also higher in lung and liver of LCN, compared to WT, mice, following exposure to NA at 5 or 10 ppm. Despite the large increase in circulating and lung tissue NA levels, the level of NA-GSH, a biomarker of NA bioactivation, was either not different, or only slightly higher, in lung and liver tissues of LCN mice, relative to that in WT mice. Furthermore, the extent of NA-induced acute airway injury, judging from high-resolution lung histopathology and morphometry at 20 h following NA exposure, was not higher, but lower, in LCN than in WT mice. These results, while confirming the ability of extrahepatic organ to bioactivate inhaled NA and mediate NA's lung toxicity, suggest that liver P450-generated NA metabolites also have a significant, although relatively small, contribution to airway toxicity of inhaled NA. This hepatic contribution to the airway toxicity of inhaled NA may be an important risk factor for individuals with diminished bioactivation activity in the lung. [ABSTRACT FROM AUTHOR]

[Display omitted] • DSF inhibited necrosis in both freshly isolated acinar cells and pancreatic tissue of AP mice. • DSF inhibited the activation of RIPK1 in acinar cells and pancreas of AP mice. • DSF strikingly inhibited the formation of NETs induced by DAMPs released by necrotic acinar cells. Acute pancreatitis (AP) is a frequent abdominal inflammatory disease. Despite the high morbidity and mortality, the management of AP remains unsatisfactory. Disulfiram (DSF) is an FDA-proved drug with potential therapeutic effects on inflammatory diseases. In this study, we aim to investigate the effect of DSF on pancreatic acinar cell necrosis, and to explore the underlying mechanisms. Cell necrosis was induced by sodium taurocholate or caerulein, AP mice model was induced by nine hourly injections of caerulein. Network pharmacology, molecular docking, and molecular dynamics simulation were used to explore the potential targets of DSF in protecting against cell necrosis. The results indicated that DSF significantly inhibited acinar cell necrosis as evidenced by a decreased ratio of necrotic cells in the pancreas. Network pharmacology, molecular docking, and molecular dynamics simulation identified RIPK1 as a potent target of DSF in protecting against acinar cell necrosis. qRT-PCR analysis revealed that DSF decreased the mRNA levels of RIPK1 in freshly isolated pancreatic acinar cells and the pancreas of AP mice. Western blot showed that DSF treatment decreased the expressions of RIPK1 and MLKL proteins. Moreover, DSF inhibited NF-κB activation in acini. It also decreased the protein expression of TLR4 and the formation of neutrophils extracellular traps (NETs) induced by damage-associated molecular patterns released by necrotic acinar cells. Collectively, DSF could ameliorate the severity of mouse acute pancreatitis by inhibiting RIPK-dependent acinar cell necrosis and the following formation of NETs. [ABSTRACT FROM AUTHOR]

Surface enhanced Raman scattering (SERS) has been developed as a powerful tool for detection of ultra-trace molecules, thus at foundation of a number of important technologies, such as chemical analysis and biosensor. Photocatalytic growth of Ag nanoparticles (NPs) by TiO 2 film is a cost-effective, facile and surfactantless way to fabricate SERS substrates with high stability and reproducibility, but the SERS activity still needs to be improved. In this work, we report a facile way to improve SERS activity of TiO 2 -catalyzed Ag NPs by additionally depositing a layer of Ag film using magnetron sputtering. Combining with the advantages of liquid and vapor environment, the Ag NPs size increase to the resonance size without decrease of density, so the spacing of Ag NPs decrease and high-density hotspots can be formed. By optimizing the sputtering time of Ag films, the SERS activity of the Ag NPs/films is improved by a factor of ∼400. This work not only establish a low-cost method for fabricating high-quality SERS substrate, more importantly, propose a novel way to prepare plasmonic nanostructures with high-density hotspots. [ABSTRACT FROM AUTHOR]

Depression is an inflammatory disorder. Pro-inflammatory cytokine interleukin-1 beta (IL-1β) may play a pivotal role in the central nervous system (CNS) inflammation of depression. Here, we investigated IL-1β alteration in serum, cerebrospinal fluid (CSF) and prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS)-exposed rats, a well-documented model of depression, and further explored the molecular mechanism by which CUMS procedure induced IL-1β-related CNS inflammation. We showed that 12-week CUMS procedure remarkably increased PFC IL-1β mRNA and protein levels in depressive-like behavior of rats, without significant alteration of serum and CSF IL-1β levels. We found that CUMS procedure significantly caused PFC nuclear factor kappa B (NF-κB) inflammatory pathway activation in rats. The intriguing finding in this study was the induced activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome with the increased IL-1β maturation in PFC of CUMS rats, suggesting a new grade of regulatory mechanism for IL-1β-related CNS inflammation. Moreover, microglial activation and astrocytic function impairment were observed in PFC of CUMS rats. The increased co-location of NLRP3 and ionized calcium binding adaptor molecule 1 (Iba1) protein expression supported that microglia in glial cells was the primary contributor for CUMS-induced PFC NLRP3 inflammasome activation in rats. These alterations in CUMS rats were restored by chronic treatment of the antidepressant fluoxetine, indicating that fluoxetine-mediated rat PFC IL-1β reduction involves both transcriptional and post-transcriptional regulatory mechanisms. These findings provide in vivo evidence that microglial NLRP3 inflammasome activation is a mediator of IL-1β-related CNS inflammation during chronic stress, and suggest a new therapeutic target for the prevention and treatment of depression. [ABSTRACT FROM AUTHOR]

TRAM-34, a clotrimazole analog characterized as a potent and selective inhibitor of intermediate-conductance, calcium-activated K+ (IKCa) channels, has been used extensively in vitro and in vivo to study the biological roles of these channels. The major advantage of TRAM-34 over clotrimazole is the reported lack of inhibition of the former drug on cytochrome P450 (CYP) activity. CYPs, a large family of heme-containing oxidases, play essential roles in endogenous signaling and metabolic pathways, as well as in xenobiotic metabolism. However, previously published work has only characterized the effects of TRAM-34 on a single CYP isoform. To test the hypothesis that TRAM-34 may inhibit some CYP isoforms, the effects of this compound were presently studied on the activities of four rat and five human CYP isoforms. TRAM-34 inhibited recombinant rat CYP2B1, CYP2C6 and CYP2C11 and human CYP2B6, CYP2C19 and CYP3A4 with IC50 values ranging from 0.9 µM to 12.6 µM, but had no inhibitory effects (up to 80 µM) on recombinant rat CYP1A2, human CYP1A2, or human CYP19A1. TRAM-34 also had both stimulatory and inhibitory effects on human CYP3A4 activity, depending on the substrate used. These results show that low micromolar concentrations of TRAM-34 can inhibit several rat and human CYP isoforms, and suggest caution in the use of high concentrations of this drug as a selective IKCa channel blocker. In addition, in vivo use of TRAM-34 could lead to CYP-related drug-drug interactions. [ABSTRACT FROM AUTHOR]

Summary: Epidemiological evidence demonstrates the neuroendocrine link between stress, depression and diabetes. This study observed glucose intolerance of rats exposed to chronic unpredictable mild stress (CUMS) in oral glucose tolerance test (OGTT). CUMS procedure significantly up-regulated corticotropin-releasing factor (CRF)-related peptide urocortin 2 expression and elevated cAMP production, resulting in over-expression of suppressor of cytokine signaling 3 (SOCS3) in hypothalamic arcuate nucleus (ARC) of rats. Furthermore, SOCS3 activation blocked insulin signaling pathway through the suppression of insulin receptor substrate 2 (IRS2) phosphotyrosine and phosphatidylinositol-3-kinase (PI3-K) activation in hypothalamic ARC of CUMS rats after high-level of insulin stimulation. These data indicated that CUMS procedure induced the hyperactivity of CRF system, and subsequently produced conditional loss of insulin signaling in hypothalamic ARC of rats. More importantly, icariin and fluoxetine with the ability to restrain CRF system hyperactivity improved insulin signaling in hypothalamic ARC of CUMS rats, which were consistent with the enhancement of glucose tolerance in OGTT, showing anti-diabetic efficacy. Although effective in OGTT, anti-diabetic drug pioglitazone failed to restore hypothalamic ARC CRF system hyperactivity, paralleling with its inability to ameliorate the loss of insulin signaling and depression-like behavior in CUMS rats. These observations support the hypothesis that signal cross-talk between hypothalamic CRF system and insulin may be impaired in depression with glucose intolerance and suggest that icarrin and fluoxetine aiming at CRF system may have great potential in the prevention and treatment of depression with comorbid diabetes. [ABSTRACT FROM AUTHOR]

Background: Despite the innovations in total knee arthroplasty (TKA), there is still a subset of patients who do not acquire significant relief or expected satisfaction after primary TKA. However, this subgroup of patients still gains improvements more or less in terms of objective or quantified assessments after the procedure. The purpose of our study is to explore the factors that correlate with patients' satisfaction and identify minimal clinically important difference (MCID) and minimum important change (MIC) in clinical parameters. Methods: We conducted a retrospective study of 161 patients diagnosed with osteoarthritis who underwent unilateral total knee arthroplasty from January 2017 to December 2017. We collected the following parameters: body mass index (BMI), duration of disease, education level, depression state, preoperative flexion contracture angle of knee, HSS scores, 11-point NRS scores, and radiological parameters (preoperative minimal joint space width and varus angle of knee). The satisfaction was graded by self-reported scores in percentage (0–100). Results: We revealed that 80.8% of patients were satisfied 3 years overall after primary TKA. HSS score change, NRS-Walking score change, age, and pre-mJSW showed significant difference between satisfied and dissatisfied group. The varus angle change revealed statistical significance according to the levels of satisfaction. Simple linear regression identified the MCID for HSS score to be 5.41 and for the NRS-Walking to be 1.24. The receiver operating characteristics (ROC) curve identified the MIC for HSS score to be 25.5 and for the NRS-Walking score to be 6.5. Conclusions: In summary, we identified several factors that correlated with patients' satisfaction independently after TKA in a long term. In addition, we revealed the minimal clinically important difference (MCID) and minimum important change (MIC) for HSS and NRS score in these patients. [ABSTRACT FROM AUTHOR]

The optical property of three-dimensional (3D) hybrid nanostructures consisting of Ag-coated SiO2 nanorods (Ag-SiO2 NRs) is studied by a method of finite-difference time-domain calculations. In the visible-light to infrared band, the extinction spectra of single Ag-SiO2 NRs are basically dominated by three surface plasmon resonance (SPR) peaks. By calculating the electric fields of Ag-SiO2 NRs excited by the incident light in resonance with the three SRP peaks, the plasmons are identified to originate from the electronic oscillation located at the bottom, the side surface, and the top, respectively, different from the extinction behavior of spherical or semispherical Ag-coated SiO2 nanostructures. The extinction behavior of Ag-SiO2 NRs is also found to become obviously different from that of pure Ag NRs when the thickness of Ag layers is less than the penetration depth of incident light in pure silver. The plasmon coupling between the Ag-SiO2 NRs is investigated using the parallel and fork-like configurations. It is found that the parallel configurations exhibit the extinction spectra similar to those of single Ag-SiO2 NRs, while the plasmon coupling enables the local electric fields to be obviously enhanced, especially in the gap regions. For the fork-like configurations, the plasmon coupling between the Ag-SiO2 NRs results in the enhanced electromagnetic radiation normal to the polarization direction of incident light, forming the hybridized plasmons generated by the electronic oscillations with different nodes.Graphical Abstract: The optical property of three-dimensional (3D) hybrid nanostructures consisting of Ag-coated SiO2 nanorods (Ag-SiO2 NRs) is studied by a method of finite-difference time-domain calculations. In the visible-light to infrared band, the extinction spectra of single Ag-SiO2 NRs are basically dominated by three surface plasmon resonance (SPR) peaks. By calculating the electric fields of Ag-SiO2 NRs excited by the incident light in resonance with the three SRP peaks, the plasmons are identified to originate from the electronic oscillation located at the bottom, the side surface, and the top, respectively, different from the extinction behavior of spherical or semispherical Ag-coated SiO2 nanostructures. The extinction behavior of Ag-SiO2 NRs is also found to become obviously different from that of pure Ag NRs when the thickness of Ag layers is less than the penetration depth of incident light in pure silver. The plasmon coupling between the Ag-SiO2 NRs is investigated using the parallel and fork-like configurations. It is found that the parallel configurations exhibit the extinction spectra similar to those of single Ag-SiO2 NRs, while the plasmon coupling enables the local electric fields to be obviously enhanced, especially in the gap regions. For the fork-like configurations, the plasmon coupling between the Ag-SiO2 NRs results in the enhanced electromagnetic radiation normal to the polarization direction of incident light, forming the hybridized plasmons generated by the electronic oscillations with different nodes. [ABSTRACT FROM AUTHOR]

Pyrrolizidine alkaloids (PAs) are common phytotoxins with both hepatotoxicity and pneumotoxicity. Hepatic cytochrome P450 enzymes are known to bioactivate PAs into reactive metabolites, which can interact with proteins to form pyrrole-protein adducts and cause intrahepatic cytotoxicity. However, the metabolic and initiation biochemical mechanisms underlying PA-induced pneumotoxicity remain unclear. To investigate the in vivo metabolism basis for PA-induced lung injury, this study used mice with conditional deletion of the cytochrome P450 reductase (Cpr) gene and resultant tissue-selective ablation of microsomal P450 enzyme activities. After oral exposure to monocrotaline (MCT), a pneumotoxic PA widely used to establish animal lung injury models, liver-specific Cpr-null (LCN) mice, but not extrahepatic Cpr-low (xh-CL) mice, had significantly lower level of pyrrole-protein adducts in the serum, liver and lungs compared with wild-type (WT) mice. While MCT-exposed LCN mice had significantly higher blood concentration of intact MCT, compared to MCT-exposed WT or xh-CL mice. Consistent with the MCT in vivo bioactivation data, MCT-induced lung injury, represented by vasculature damage, in WT and xh-CL mice but not LCN mice. Furthermore, reactive metabolites of MCT were confirmed to exist in the blood efflux from the hepatic veins of MCT-exposed rats. Our results provide the first mode-of-action evidence that hepatic P450s are essential for the bioactivation of MCT, and blood circulating reactive metabolites of MCT to the lung causes pneumotoxicity. Collectively, this study presents the scientific basis for the application of MCT in animal lung injury models, and more importantly, warrants public awareness and further investigations of lung diseases associated with exposure to not only MCT but also different PAs. [ABSTRACT FROM AUTHOR]

The effect of variations in the expression of cytochrome P450 reductase (CPR or POR) is determined in mice with decreased POR expression to identify potential vulnerabilities in people with low POR expression. There is an age-dependent appearance of increasing vacuolization in the proximal tubules of the renal cortex in 4- to 9-month-old male (but not female) Cpr-low (CL) mice. These mice have low POR expression in all cells of the body and upregulation of lysosome-associated membrane protein 1 expression in the renal cortex. Vacuolization is also seen in extrahepatic CL and extrarenal CL male mice, but not in mice with tissue-specific Por deletion in liver, intestinal epithelium, or kidney. The occurrence of vacuolization is accompanied by increases in serum blood-urea-nitrogen levels. Male CL mice are hypersensitive to cisplatin- and gentamicin-induced renal toxicity at 3 months of age, before proximal tubular (PT) vacuoles are detectable. At doses that do not cause renal toxicity in wild-type mice, both drugs cause substantial increases in serum blood-urea-nitrogen levels and PT vacuolization in male but not female CL mice. The hypersensitivity to drug-induced renal toxicity is accompanied by increases in circulating drug levels. These novel findings demonstrate deficiency of renal function in mice with globally reduced POR expression and suggest that low POR expression may be a risk factor for drug-induced nephrotoxicity in humans. [ABSTRACT FROM AUTHOR]

• A twin elliptical die whose junction is smoothly connected is designed. • The drawing force of the twin elliptical die is the smallest compared with those based on the conical die and the single elliptical die. • A higher reduction leads to the increase of the optimal die angle at a specific friction factor. According to the stream function requirement, a twin elliptical die for rod or wire drawing is designed, and the subsequent plastic mechanical analysis is carried out. In terms of the volume constant condition, a kinematically admissible velocity field describing the drawing process is constructed. Based on the velocity field, the analytical expression of internal plastic deformation energy rate accounting for the non-zero shear strain rate is obtained by using the mean value theorem of integral. Then, the analytical expression of friction energy rate is also derived by the mean value theorem of integral. Ultimately, the analytical expression of the drawing force is obtained based on the upper bound method. It is found that there exists the optimal die semi-angle which depends on the relative reduction and friction factor. The analytical drawing force based on the twin elliptical die is validated by the corresponding simulated results, and a very agreement is found since the relative errors between them are less than 9.2%. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp) is an important factor leading to multidrug resistance (MDR) in cancer treatment. The co-administration of anticancer drugs and P-gp inhibitors has been a treatment strategy to overcome MDR. In recent years, tyrosine kinase inhibitor Lapatinib has been reported to reverse MDR through directly interacting with ABC transporters. In this work, a series of P-gp inhibitors (1–26) was designed and synthesized by integrating the quinazoline core of Lapatinib into the molecule framework of the third-generation P-gp inhibitor Tariquidar. Among them, compound 14 exhibited better MDR reversal activity than Tariquidar. The docking results showed compound 14 displayed the L-shaped molecular conformation. Importantly, compound 14 increased the accumulation of Adriamycin (ADM) and rhodamine 123 (Rh123) in MCF7/ADM cells. Besides, compound 14 significantly increased ADM-induced apoptosis and inhibited the proliferation, migration and invasion of MCF7/ADM cells. It was also demonstrated that compound 14 significantly inhibited the growth of MCF7/ADM xenograft tumors by increasing the sensitivity of ADM. In summary, compound 14 has the potential to overcome MDR caused by P-gp. [Display omitted] • Novel P-gp inhibitors were designed, synthesized and bioevaluated. • Compound 14 exhibits better MDR reversal activity than third-generation P-gp inhibitor Tariquidar. • Compound 14 inhibited the efflux function of P-gp. • Compound 14 significantly inhibited the growth of MCF7/ADM xenograft tumors. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 15 (FGF15) was previously identified to be highly expressed in the ileum and functions as an endocrine factor to regulate bile acid synthesis in the liver. FGF15 targets its receptor fibroblast growth factor receptor 4 in the liver and serves important roles in energy metabolism, including bile acid homeostasis, glucose metabolism and protein synthesis. The expression of FGF15 is known to be regulated by the transcription factor farnesoid X receptor (FXR). In the present study, reverse transcription-quantitative polymerase chain reaction was used for measuring Fgf15 expression from the animal and tissue culture experiments, and it was identified that dexamethasone, a drug widely used in anti-inflammation therapy, and a classical inducer of glucocorticoid receptor (GR)- and pregnane X receptor (PXR)-target genes, may downregulate Fgf15 expression in the ileum. GR was identified to be highly expressed in the ileum by western blot analysis. Furthermore, it was demonstrated that the downregulation of Fgf15 by dexamethasone is due to the repression of ileal FXR activity via GR; however, not PXR, in the ileum. The present results provide insight for a better understanding of the adverse effects associated with dexamethasone therapy. [ABSTRACT FROM AUTHOR]

Many flaviviruses, such as Zika virus (ZIKV), Dengue virus (DENV1-4) and yellow fever virus (YFV), are significant human pathogens. Infection with ZIKV, an emerging mosquito-borne flavivirus, is associated with increased risk of microcephaly in newborns and Guillain-Barré syndrome and other complications in adults. Currently, specific therapy does not exist for any flavivirus infections. In this study, we found that erythrosin B, an FDA-approved food additive, is a potent inhibitor for flaviviruses, including ZIKV and DENV2. Erythrosin B was found to inhibit the DENV2 and ZIKV NS2B-NS3 proteases with IC 50 in low micromolar range, via a non-competitive mechanism. Erythrosin B can significantly reduce titers of representative flaviviruses, DENV2, ZIKV, YFV, JEV, and WNV, with micromolar potency and with excellent cytotoxicity profile. Erythrosin B can also inhibit ZIKV replication in ZIKV-relevant human placental and neural progenitor cells. As a pregnancy category B food additive, erythrosin B may represent a promising and easily developed therapy for management of infections by ZIKV and other flaviviruses. [ABSTRACT FROM AUTHOR]

• The alternating magnetic field changes arc morphology and reduces droplet size. • Appropriate excitation current effectively reduces surface roughness. • The alternating magnetic field can effectively refine the grains and deflect the grains growth direction. In this paper, the bead geometric characteristics, droplet transfer behavior and microstructure of wire arc additive manufactured Inconel 718 alloy using cold metal transfer process assisted by an alternating magnetic field (AMF) are investigated by varying the excitation current. The results show that the AMF reduces the droplet size from 1.7 mm to 1.4 mm, and changes the arc shape from bell shape to "broom shape". With increasing excitation current, the surface roughness first drops from 0.14 at 0 A to 0.08 at 20 A and then rises to 0.25 at 40 A, finally reaching a maximum value of 0.39 at 60 A. The grain growth direction is deflected along the build direction by the AMF, and the average grain size decreases to 69.5 μm. [ABSTRACT FROM AUTHOR]

In this work, a serial of Fe/Fe 3 N based nanocomposites were synthesized by high-temperature pyrolytic method. Structural characterizations show that the small Fe/Fe 3 N nanoparticles uniformly dispersed on the surface of carbon films, where thin carbon may effectively enhance the stability of Fe/Fe 3 N and the carbon films can accelerate the migration of electrons. Moreover, Fe/Fe 3 N based composite can significantly increase the effective area of bare GCE because of its high conductivity, large surface area, and good catalytic property. These structural advantages enhance the electrochemical performance of the constructed electrodes toward simultaneous dopamine (DA) and acetaminophen (AP) sensing. Under optimum condition, the linear ranges for DA and AP detection were 0.05–66.4 μM and 0.05–56.9 μM, respectively. In addition, due to its high sensitivity, good selectivity and strong stability, Fe/Fe 3 N-900@GCE can also be applied for detecting DA and AP in real samples. This work provides a simple and effective strategy for constructing new electrode materials for small biomolecule sensing. Core-Shell Fe/Fe 3 N/carbon nanocomposites were synthesized by high-temperature pyrolytic method, and were developed as electrochemical sensors for dopamine and acetaminophen detection. [Display omitted] • Core-shell Fe/Fe 3 N/carbon composite was prepared by high-temperature pyrolytic method. • The carbon shells enhance the stability of Fe/Fe 3 N@C and accelerate the migration of electrons. • The construct electrode reveals high sensitivity toward simultaneous sensing of DA and AP. • The construct electrode can be used to detect DA and AP in commercial medicines. [ABSTRACT FROM AUTHOR]

In this study, the microstructure, mechanical properties and fracture mechanism of wire arc additive manufactured Inconel 718 alloy fabricated by cold metal transfer process under the action of the alternating magnetic field (AMF) are studied by changing the excitation current. The results show that the AMF deflects the droplet and changes the direction of the molten pool maximum temperature gradient, which inhibits the growth of large columnar crystals and refines the grains so that the index of {100}<001> texture decreases significantly. The microstructure of the 0 A and 40 A samples is composed of γ(Ni) + (TiN) [nucleus]/(NbC + TiC)[shell] + NbC + Laves. The length of γʹʹ-Ni 3 Nb of the 0 A sample (98 nm) is greater than that of the 40 A sample (84 nm). The AMF suppresses the large columnar crystals, and the average grain size is reduced to 161 μm. The volume fraction of the Laves phases is significantly reduced from 2.4% to 1.3%, and the Laves phases morphology changes from long stripe to granular under the action of the AMF. AMF increases the ultimate tensile strength and decreases the anisotropy. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant-based interventions can inhibit the ROS-TXNIP pathway. Antioxid. Redox Signal. 22, 848-870. [ABSTRACT FROM AUTHOR]

Using a patterned sapphire substrate with a hemisphere array, flower-like ZnO nanorods grouped in a highly ordered array were fabricated on the wafer scale by routine solution growth. After decorating with high-density Ag nanoparticles (NPs), the ZnO nanoflower arrays were used as the substrates for surface enhanced Raman scattering (SERS). Using Rhodamine 6G as the probe molecules with a concentration down to 10−10 M, the SERS substrates present an as high as 1010 Raman enhancement with good reproducibility. The influence of Ag NP decoration on the SERS activity was explored and the sub-10 nm nanogaps between the adjacent Ag NPs were proved to be the primary electromagnetic “hot spots” responsible for the significant Raman enhancement. The Ag-NP-decorated ZnO nanoflower arrays were demonstrated to possess a self-cleaning function enabled by UV irradiation via photocatalytic degradation of the analyte molecules. In addition, the SERS substrate exhibited an extremely long service lifetime, possibly due to its superhydrophobicity and storage in the dark and a dry environment. [ABSTRACT FROM AUTHOR]

P450-mediatedbioactivation of azoxymethane (AOM), a colon carcinogen,leads to the formation of DNA adducts, of which O6-methylguanine (O6-mG) is the most mutagenicand contributes to colon tumorigenesis. To determine whether P450enzymes of the liver and intestine both contribute to AOM bioactivation in vivo, we compared tissue levels of AOM-induced DNA adducts,microsomal AOM metabolic activities, and incidences of colonic aberrantcrypt foci (ACF) among wild-type (WT), liver-specific P450 reductase(Cpr)-null (LCN), and intestinal epithelium-specific Cpr-null (IECN)mice. At 6 h following AOM treatment (at 14 mg/kg, s.c.), O6-mG and N7-mG levels were highest in the liver, followedby the colon, and then small intestine in WT mice. As expected, hepaticadduct levels were significantly lower (by >60%) in LCN mice butunchangedin IECN mice, whereas small-intestinal adduct levels were unchangedor increased in LCN mice but lower (by >50%) in IECN mice comparedto that in WT mice. However, colonic adduct levels were unchangedin IECN mice compared to that in WT mice and increased in LCN mice(by 1.5–2.9-fold). The tissue-specific impact of the CPR lossin IECN and LCN mice on microsomal AOM metabolic activity was confirmedby rates of formation of formaldehyde and N7-mG in vitro. Furthermore, the incidence of ACF, a lesion precedingcolon cancer, was similar in the three mouse strains. Thus, AOM-inducedcolonic DNA damage and ACF formation is not solely dependent on eitherhepatic or intestinal microsomal P450 enzymes. P450 enzymes in boththe liver and intestine likely contribute to AOM-induced colon carcinogenesis. [ABSTRACT FROM AUTHOR]

Highlights: [•] GPs pre-treatment reduces the infarct volume and improve motor function in MCAO rats. [•] GPs pre-treatment promotes cellular proliferation within the SVZ. [•] GPs pre-treatment enhances the neurogenesis within the SVZ. [ABSTRACT FROM AUTHOR]

Cerous phosphate (CePO 4) is attracting increasing attentions due to its potential sensing properties. But so far, the effect of morphology on its electrochemical sensing performance is scarcely reported. In this work, a bowknot-like CePO 4 (B–CePO 4) has been hydrothermally synthesized and characterized using XRD, BET, SEM, TEM, FT-IR spectroscopy and UV–Vis spectroscopy. It was shown that both the reaction time and the amount of urea had an important influence on the formation of CePO 4 bowknots. The constructed B–CePO 4 showed hierarchical structure and enhanced electron transfer ability. Then, it was utilized as an effective sensor for electrochemical sensing of ascorbic acid (AA) with wide linear range of 5.0–2150 ​ μ M, low detect limitation of 0.51 ​ μ M, high selectivity, good repeatability, and high stability. Furthermore, the B–CePO 4 can also be used to detect AA in commercial vitamin tablets. In addition, due to its good fluorescent performance, B–CePO 4 was used for fluorescence detecting of AA. This work provides an effective strategy for exploring new nanomaterials for sensing biomolecules. A bowknot-like cerous phosphate was prepared using a simple hydrothermal method, and was developed as a bifunctional sensor for electrochemical and fluorescent detection of AA. [Display omitted] • Bowknot-like CePO 4 with hierarchical structure was hydrothermally synthesized. • The formation of bowknot-like CePO 4 is closely related to reaction time and the amount of urea. • The bowknot-like CePO 4 was used as a bifunctional sensor for electrochemical and fluorescent AA sensing. • This work provides an effective strategy for exploring new nanomaterials for sensing biomolecules. [ABSTRACT FROM AUTHOR]

Reactive sputtering deposition has been widely applied to the preparation of oxide films, but a method is still needed to stably control the deposition process and the film growth. In this work, the plasma in the vicinity of sputtering target is studied by optical emission spectroscopy and the atomic oxygen density ([O]) is linked to the sputtering mode and the growth of NiO films. The NiO films can be deposited either in oxide mode or in the transition region, whereas the [O] value plays an important role in determining the growth behavior of NiO films and the crystallinity. In the transition region, the (111)-oriented growth of NiO films is preferential and the crytallinity is improved with the decrease in the [O] value. In the oxide mode, the NiO films are preferentially (001)-oriented and exhibit a relatively good crystallinity. By fixing the O 2 /Ar flow ratio at a constant, the [O] value is explored as a function of substrate temperature, showing that the oxygen desorption may have significant impacts on the [O] value as the substrate temperature is higher than 400 °C. • Determining the role of atomic oxygen in reactive sputtering deposition of NiO films. • Establishing an OES method of determining atomic oxygen density. • Linking the growth behavior of NiO films being to atomic oxygen density. [ABSTRACT FROM AUTHOR]

Abstract: ZnO films are hydrothermally grown on ZnO-buffered c-plane sapphire substrates at a low temperature of 70°C. A radio-frequency (RF) reactive magnetron sputtering has been used to grow the ZnO buffer layers. X-ray diffraction, scanning electron microscopy, and room temperature photoluminescence are carried out to characterize the structure, morphology and optical property of the films. It is found that the films are stress-free. The epitaxial relationship between the ZnO film and the c-plane sapphire substrate is found to be ZnO (0001)||Al2O3 (0001) in the surface normal and in plane. Sapphire treatment, as such acid etching, nitridation, and oxidation are found to influence the nucleation of the film growth, and the buffer layers determine the crystalline quality of the ZnO films. The maximum PL quantum efficiency of ZnO films grown with hydrothermal method is found to be about 80% of single-crystal ZnO. [Copyright &y& Elsevier]

Abstract: An ab initio calculation based on density functional theory is applied to study the doping stability and electronic structure of wurtzite Zn1−x Cd x O alloys. It is found that the different alloy configurations of Zn1−x Cd x O with a given Cd content are possible thermodynamically, but having different band gaps. With increasing Cd content, the formation enthalpy of Zn1−x Cd x O alloy increases sharply. The Cd-content dependence of the band-gap values can be fitted with a second-order polynomial. The reduction of band gap can be attributed to the contributions of the hybridization of Zn-4s and Cd-5s, the enhancement of p–d repulsion, and the tensile strain due to Cd-doping. [Copyright &y& Elsevier]

Background: MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology. Methods: The human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay. Results: Upregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222. Conclusion: These results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR- 221 and miR-222 might form a novel therapeutic strategy for human gastric cancer. [ABSTRACT FROM AUTHOR]

Nickel nanoparticles loaded with carbon nanorods were facile synthesized by pyrolysis of a Ni-based coordination compound. The constructed composite shows outstanding sensing performance for dopamine and uric acid. In addition, the constructed composite can also be utilized for real sample analysis. [Display omitted] • Rod-shape Ni@CNRs were facile synthesized by pyrolysis of a Ni-based coordination compound. • The high special surface area of Ni@CNRs can increase the exposure of active sites. • Uniformly distribution of Ni nanoparticles on the surface of CNRs is beneficial to the electron migration. • The Ni@CNRs was used as an effective electrochemical probe for simultaneous dopamine and uric acid detection. • The application of Ni@CNRs provides an effective strategy for exploring new electrical sensing materials. Nickel nanoparticles loaded with carbon nanorods (Ni@CNRs) were facile synthesized by pyrolysis of a Ni-based coordination compound. The constructed Ni@CNRs hybrid showed a high special surface area with Ni nanoparticles uniformly distributing on its surface. It is expected that the high special surface area of Ni@CNRs may increase the exposure of active sites, whereas the uniformly distribution of Ni nanoparticles may shorten the gap between Ni nanoparticles and CNRs, and then speeds up the electron migration. Then, Ni@CNRs were used as effective electrochemical sensor for simultaneous dopamine (DA) and uric acid (UA) detection. It is found that Ni@CNRs modified electrode exhibited two linear ranges of 0.5–30 μM and 35–100 μM for both single detection of DA and UA. The detection limits (S/N = 3) were calculated to be 0.056 μM for DA and 0.166 μM for UA, respectively. In addition, due to its high sensitivity and stability, Ni@CNRs was successfully applied for DA and UA analysis in human urine. These results show that Ni@CNRs is an effective electrode material for DA and UA detection. This work provides an effective strategy for exploring new electrical sensing materials. [ABSTRACT FROM AUTHOR]

Abstract: Knowing the atomistic processes of low-energy impact is crucial for understanding the mechanisms of energetic deposition. In this study, molecular dynamics techniques were used to simulate the impact of low-energy Pt atoms on Pt (111) doped with Cu, Ag, Au, Ni, and Pd atoms using an atomic interaction potential with an embedded atom method. We studied the dependence of adatom creation, sputtering behavior, and vacancy creation on the incident energy of Pt atoms in the range 0.1 to 200 eV. It is found that doping with noble metal atoms may enable adatom yields, sputter yields, and vacancy yields to be changed. This variation can be attributed to the mass effect of dopants. Preferential sputtering of light dopants results in a reduction in the threshold energy for sputtering. We also found the cohesive energy of Pt atoms and the threshold energy for sputtering to be the measures dominating the interaction of low-energy Pt atoms with doped Pt (111) surfaces. A model based on a reflection mechanism of incident atoms in the framework of binary collision theory is suggested to describe the interaction of low-energy atoms with the doped Pt (111) surface. [Copyright &y& Elsevier]

The aim of the present study was to further characterize the expression of the CYP2A genes in human nasal mucosa. Fetal nasal tissues at 12–26 weeks of gestational age and surgical biopsy tissues from various regions of nasal cavity of adult patients were studied to determine whether CYP2A proteins can be detected by immunoblot in adults, whether higher levels of CYP2A proteins are present in adult than in fetal nasal mucosal microsomes, and whether CYP2A13 mRNA is more abundant than CYP2A6 mRNA in fetal nasal mucosa. In adults, immunoblot analysis detected CYP2A proteins in microsomes of the olfactory region from 8 of 10 individuals, but in none of the nasal microsomes of the respiratory region from 47 patients. Quantitative immunoblot analysis confirmed that CYP2A proteins are selectively expressed in the olfactory region in both adult and fetal tissues. Interestingly, the levels of CYP2A proteins in nasal microsomes were generally higher in fetuses than in adults. In the fetus, the level of CYP2A13 mRNA was much higher than that of CYP2A6 mRNA, as has been previously found in adult nasal mucosa. Immunohistochemical studies confirmed that, in the fetus, the CYP2A proteins are expressed in the supporting cells in the olfactory epithelium and in the Bowman’s glands in the lamina propria. The prenatal expression of the CYP2A proteins in the olfactory mucosa suggests potential risks of developmental toxicity from maternally derived xenobiotics, since both CYP2A6 and CYP2A13 are known to be efficient in the metabolic activation of tobacco-specific nitrosamines and other respiratory toxicants. [Copyright &y& Elsevier]

R3063 --> CYP19A1 (the aromatase) is a key enzyme in the biosynthesis of estrogens, which have important regulatory functions, including roles as a major mitogenic stimulus for cellular proliferation. Using a new myeloid cell‐specific Cyp19a1‐null (Cyp19a1‐null) mouse model, we tested the role of macrophage CYP19A1 in pulmonary regenerative response to naphthalene‐induced bronchiolar epithelial cell injury. Wild‐type and Cyp19a1‐null mice were treated with naphthalene (200 mg/kg, IP) to induce acute lung injury, or with corn oil as a vehicle control. Mouse lung was examined at 24 hour, 72 hours, or 14 days after the treatment, for extent of acute airway injury, post‐injury cellular proliferation, and tissue repair, respectively. At 24 hours, a genotype difference in the extent of naphthalene‐induced airway injury was not detected. At 72 hours, the fraction of airway epithelial cells that are positive for the cell proliferation marker Ki67 was higher in naphthalene‐treated wild‐type mice (40%‐70%) than in naphthalene‐treated Cyp19a1‐null mice (20‐30%); whereas the fraction was much lower in corn oil treated control mice (3‐5%). At 14 days, the bronchiolar epithelium was recovered to a greater extent in wild‐type (~80%) than in the Cyp19a1‐null mice (<30%), as indicated by the abundance of Club cells (positive for Club cell secretary protein) in the airway epithelium. Further studies of isolated macrophages indicated that Cyp19a1‐null macrophages had reduced phagocytosis (by ~70%) and migration (by ~50%) activities, compared to wild‐type controls. Thus, the loss of macrophage CYP19A1negativelyimpacted macrophage function and impeded the post‐injury cellular proliferation and tissue repair in the lung airways. [ABSTRACT FROM AUTHOR]