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BACKGROUND Shift work is associated with reduced performance and efficiency, the current study aimed at investigating whether blue-enriched white light could improve workers' performance. METHODS The study, which adopted a randomized controlled trial, was conducted among 48 simulated shift workers. The participants performed sustained attention task, working memory task, and sleepiness task during night shift work. The data was analyzed using two-way repeated measure ANOVA. RESULTS The results indicated that, compared to conventional light, participants' correct responses of the sustained attention significantly increased when they were exposed to blue-enriched white light, correspondingly, the commission errors and omission errors declined. Furthermore, the blue-enriched white light had a significant effect on the decrease of sleepiness. However, the working memory was not significantly affected. CONCLUSION Exposing to blue-enriched white light can improve sustained attention and reduce sleepiness.

One immunomagnetic separation (IMS) assay based on immunomagnetic beads (IMBs) has been evaluated as a potential pretreatment tool for the separation and enrichment of target bacteria. In this study, we successfully immobilized antibodies onto magnetic bead surfaces to form IMBs through biotin and a streptavidin (SA) system to capture viable but nonculturable (VBNC) Cronobacter sakazakii (C. sakazakii) from dairy products. Various parameters that affected the capture efficiency (CE) of IMS, including the number of antibodies, IMBs dose, incubation time, magnetic separation time, and immunoreaction temperature, were systematically investigated. We further determined the optimal enrichment conditions for different dairy substrates to ensure maximum enrichment of target pathogens in the system. An IMS technique combining improved propidium monoazide (PMAxx) and droplet digital PCR (ddPCR) was established to detect the pathogenic VBNC C. sakazakii. The IMS-PMAxx-ddPCR method after IMBs enrichment showed higher accuracy when the VBNC C. sakazakii was under 1 Log10 copies/g. The detection limit for this method in a background of powdered infant formula (PIF) was 5.6 copies/g. In summary, the developed IMS-PMAxx-ddPCR method has great potential for the analysis and detection of VBNC bacteria in food.

Apelin, a peptide hormone, is an endogenous ligand for G protein-coupled receptor and has been shown to be widely expressed in human and animal tissues, such as the central nervous system and adipose tissue. Recent studies indicate that the apelin/APJ system is involved in the regulation of multiple physiological and pathological processes, and it is associated with cardiovascular diseases, metabolic disorders, neurological diseases, ischemia-reperfusion injury, aging, eclampsia, deafness, and tumors. The occurrence and development of these diseases are closely related to the local inflammatory response. Oxidative stress is that the balance between oxidation and antioxidant is broken, and reactive oxygen species are produced in large quantities, causing cell or molecular damage, which leads to vascular damage and a series of inflammatory reactions. Hence, this article reviewed recent advances in the relationship between apelin/APJ and oxidative stress, and inflammation-related diseases, and highlights them as potential therapeutic targets for oxidative stress-related inflammatory diseases.

Apelin, identified as the endogenous ligand of APJ, exerts various cardiovascular effects. However, the molecular mechanism underlying the regulation of apelin expression in vascular cells is poorly described. Pioglitazone (PIO) and Krüppel-like factor 4 (KLF4) exhibit specific biological functions on vascular physiology and pathophysiology by regulating differentiation- and proliferation-related genes. The present study aimed to investigate the roles of PIO and KLF4 in the transcriptional regulation of apelin in a high-fat diet/streptozotocin rat model of diabetes and in PIO-stimulated vascular smooth muscle cells (VSMCs). Immunohistochemistry, qRT-PCR, and Western blotting assays revealed that the aorta of the Type 2 diabetes mellitus (T2DM) rat models had a high expression of apelin, PIO could decrease the expression of apelin in the PIO-treated rats. In vitro, Western blotting assays and immunofluorescent staining results showed that the basal expression of apelin was decreased but that of KLF4 was increased when VSMCs were stimulated by PIO treatment. Luciferase and chromatin immunoprecipitation assay results suggested that KLF4 bound to the GKLF-binding site of the apelin promoter and negatively regulated the transcription activity of apelin in VSMCs under PIO stimulation. Furthermore, qRT-PCR and Western blotting assay results showed that the overexpression of KLF4 markedly decreased the basal expression of apelin, but the knockdown of KLF4 restored the PIO-induced expression of apelin. In conclusion, PIO inhibited the expression of apelin in T2DM rat models to prevent diabetic macroangiopathy, and negatively regulated the gene transcription of apelin by promoting transcription of KLF4 in the apelin promoter.

V1–xMoxO2 thin films were fabricated by nanolamination of VO2/MoO3 alternating layers using atomic layer deposition (ALD) process, in which tetrakis-dimethyl-amino vanadium(IV) [V(NMe2)4] and molybdenum hexacarbonyl(VI) [Mo(CO)6] were used as vanadium and molybdenum precursors, respectively. The dopant content of V1–xMoxO2 films was controlled by adjusting MoO3 cycle percentage (PMo) in ALD pulse sequence, which varied from 2 to 10%. Effects of PMo on V1–xMoxO2 crystal structure, morphology, semiconductor-to-metal transition properties, and optical transmittance were studied. A linear reduction of phase transition temperature (Tc) by approximately −11 °C/cycle % Mo was observed for V1–xMoxO2 films within PMo ≤ 5%. Notably, dramatic enhanced luminous transmittance (Tlum = 63.8%) and solar modulation (ΔTsol = 23.5%) were observed for V1–xMoxO2 film with PMo = 7%.

Cronobacter sakazakii (C. sakazakii) in viable but nonculturable (VBNC) state might evade traditional culture detection, and pose a serious threat to food safety. The objective of this study was to establish an improved propidium monoazide (PMAxx), combined with a single intact cell droplet digital PCR (SIC ddPCR) method for rapid and absolute quantification of VBNC C. sakazakii and apply it to the detection of several infant foods. In this study, we optimized the detection conditions for C. sakazakii, and determined the optimal PMAxx final concentration (8 μM), light exposure times (10 min), annealing temperature (58 °C) and elongation time (1 min). In addition, PMAxx-SIC ddPCR demonstrated a higher detection sensitivity and accuracy relative to real-time PCR (qPCR), with 23 CFU/mL in pure culture. Furthermore, PMAxx-SIC ddPCR was used to detect VBNC C. sakazakii in the actual infant food samples. A total of 240 samples were analyzed, out of which 6 samples turned out to be positive by the traditional culture method, whereas 11 samples were found as positive by PMAxx-SIC ddPCR. These results demonstrate that the presence of VBNC may cause the conventional culture-based method to underestimate the size of microbial population.

VO2 thin films have been grown on Si(100) (VO2/Si) and fused silica substrates (VO2/SiO2) by atomic layer deposition (ALD) using tetrakis-dimethyl-amino vanadium (IV) (TDMAV) as a novel vanadium precursor and water as reactant gas. The quartz crystal microbalance (QCM) measurement was performed to study the ALD process of VO2 thin film deposition, and a constant growth rate of about 0.95 A/cycle was obtained at the temperature range of 150–200 °C. XRD measurement was performed to study the influence of deposition temperature and post-annealing condition on the crystallization of VO2 films, which indicated that the films deposited between 150 and 200 °C showed well crystallinity after annealing at 475 °C for 100 min in Ar atmosphere. XPS measurement verified that the vanadium oxidation state was 4+ for both as-deposited film and post-annealed VO2/Si film. AFM was applied to study the surface morphology of VO2/Si films, which showed a dense polycrystalline film with roughness of about 1 nm. The resistance of VO2/Si films deposited between 150 °C and 200 °C as a function of temperature showed similar semiconductor-to-metal transition (SMT) characters with the transition temperature for heating branch (Tc,h) of about 72 °C, a hysteresis width of about 10 °C and the resistance change of two orders of magnitude. The increase of Tc,h compared with the bulk VO2 (68 °C) may be attributed to the tensile stress along the c-axis in the film. Transmittance measurement of VO2/SiO2 films showed typical thermochromic property with a NIR switching efficiency of above 50% at 2 μm across the transition.

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

Apelin participates in cardiovascular functions, metabolic disease, and homeostasis disorder. However, the biological function of apelin in liver diseases, especially liver fibrosis is still under investigation. The present study aimed to investigate the expression of apelin in nonalcoholic fatty liver disease (NAFLD) and the mechanism of apelin promoting hepatic fibrosis through ERK signaling in hepatic stellate LX-2 cells. The results showed that the ALT and AST levels in serum were increased in the mice fed HFC. The histological staining revealed that hepatocellular steatosis and ballooning degeneration was severe, and fibrogenesis appeared as increased pericellular collagen deposition along with pericentral (lobular) collagen deposition in the mice fed HFC. Immunochemistry and qRT-PCR results showed that the expression of apelin and profibrotic genes was higher as compared to the control group. The in vitro experiments demonstrated that apelin-13 upregulated the transcription and translation levels of collagen type I (collagen-I) and α-smooth muscle actin (α-SMA) in LX-2 cells. The immunofluorescent staining, qRT-PCR, and Western blot results showed that the overexpression of apelin markedly increased the expression of α-SMA and cyclinD1. The LX-2 cells treated with apelin-13 displayed an increased expression of pERK1/2 in a time-dependent manner, while the pretreatment with PD98059 abolished the apelin-induced expression of α-SMA and cyclinD1. Furthermore, the in vivo and in vitro assays suggested a key role of apelin in promoting liver fibrosis, and the underlying mechanism might be ascribed to the apelin expression of profibrotic genes via ERK signaling pathway. Electronic supplementary material The online version of this article (10.1007/s11010-019-03581-0) contains supplementary material, which is available to authorized users.

Naturally fractured carbonate reservoirs have been discovered in many oilfields around the world and are characteristic of a complex, heterogeneous porosity system. The presence of large-scale cavities will have a noticeable effect on the transient pressure behavior, especially, when a well is drilled through them. The cavities are usually filled with loose materials, such as gravel, sand, and mud, due to the physical or chemical processes. Therefore fluid flow in a filled cavity may range from low-velocity Darcy flow to high-velocity non-Darcy flow. It is necessary to incorporate cavity filling effect in the type curve matching for flow behavior in fractured carbonate reservoirs. The objective of this work is to develop an efficient well testing model to analyze and interpret the transient pressure responses observed in a naturally fractured carbonate reservoir, in which a well is drilled through a filled cavity. To this end, a radial composite reservoir model including the inner and outer regions with different characteristics is proposed. The inner region is a filled cavity with a well drilled into. The outer region, a naturally fractured reservoir, is considered as a dual-porosity model in this work. The Barree-Conway model, initially proposed for a proppant-packed fracture, is applied to simulate the non-Darcy flow in the inner region. The corresponding mathematical model is developed, and a numerical solution is then obtained based on the finite difference method, which is further verified by the analytical solution under simplified flow condition. Several standard log-log type curves are provided to reveal the flow characteristics. The flow process is shown to have six flow stages in general. Subsequently, sensitivity analyses of the type curves are carried out. The calculated results show that the characteristics of the well testing type curves are influenced significantly by non-Darcy coefficients, the size of the filled cavity, and the petrophysic property ratio between inner and outer areas. Finally, the proposed model is applied to analyze and interpret two field testing examples.

Accurate and rapid identification of the live fraction of pathogenic bacteria in beef food samples has emerged as a pressing issue due to the serious threat posed by pathogens to human health. Escherichia coli O157: H7, one of the most common pathogens in beef, causes hemorrhagic colitis or hemolytic uremic syndrome and subsequently a viable but nonculturable (VBNC) state under low temperatures in which the bacteria do not grow in culture medium but remain potentially virulent. The objective of this study was to establish and evaluate a method that combines improved propidium monoazide (PMAxx) treatment with real-time loop-mediated isothermal amplification (qLAMP) for the detection and quantification of VBNC E. coli O157: H7 in beef. In this study, E. coli O157: H7 was induced to enter the VBNC state by simulating food storage conditions at −20 °C. The respiratory activity of VBNC E. coli O157: H7 was measured by flow cytometry. The optimal PMAxx final concentration was 10 μM with exposure to light for 10 min for photoactivation, which was found to completely inhibit amplification of DNA derived from dead cells. When there were low levels of VBNC microorganisms in beef samples, PMAxx was significantly more accurate and effective at distinguishing between viable and dead E. coli O157: H7 cells. The developed PMAxx-qLAMP assay remarkably exhibited both high sensitivity in pure culture and beef (30 colony-forming units/mL and 300 CFU/g, respectively) and rapidity (60 min). Especially for frozen beef samples, positive ratio was 4.71% (four out of eighty-five were positive) by PMAxx-qLAMP method and the mean measured value of positive samples was 2.04 ± 0.08 Log10 CFU/g. Therefore, PMAxx-qLAMP is an effective means for improving the detection and quantification accuracy of VBNC E. coli O157: H7 in beef.

Immunomagnetic separation (IMS) is an effective method for specific enrichment and purification of target food-borne pathogens from complex food samples. To detect viable but non-culturable (VBNC) Vibrio parahaemolyticus (V. parahaemolyticus) with greater accuracy and sensitivity, we used an improved propidium monoazide (PMAxx) dye to eliminate dead cell interference in an IMS-PMAxx-real-time (quantitative) polymerase chain reaction (IMS-PMAxx-qPCR) assay. We prepared immunomagnetic beads (IMBs) using streptavidin-conjugated magnetic nanoparticles and biotinylated polyclonal antibodies, and optimized the reaction conditions to establish an IMS method for VBNC V. parahaemolyticus. We determined the optimal antibody amount (30 μg), IMBs volume (150 μL), incubation time (45 min), immunomagnetic separation time (4 min), and separation temperature (25 °C). The IMS-PMAxx-qPCR method could detect VBNC V. parahaemolyticus in raw shrimp samples at levels as low as 1.85 CFU/g without any pre-enrichment. The IMS-PMAxx-qPCR assay is highly sensitive, selective, simple, and rapid (

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Apelin is an endogenous peptide that is a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1). The apelin/APJ system is distributed in diverse periphery organ tissues. It has been shown that the apelin/APJ system plays various roles in physiology and pathophysiology of many organs. It regulates cardiovascular development or cardiac disease, glycometabolism and fat metabolism as well as metabolic disease. The apelin/APJ system participates in various cell activities such as proliferation, migration, apoptosis or inflammation. However, apelin/APJ function in the liver is still under investigation. In the liver, the apelin-APJ system could play an inhibitory role in liver regeneration and promote Fas-induced apoptosis. It may participate in the formation of hepatic fibrosis or cirrhosis, and even cancer. In this review, we summarize the role of the apelin/APJ system in liver disease.

Previous studies have demonstrated that both retinoids and apelin possess potent cardiovascular properties and that retinoids can mediate the expression of many genes in the cardiovascular system. However, it is not clear whether and how retinoids regulate apelin expression in rat VSMCs (vascular smooth muscle cells). In the present study, we investigated the molecular mechanism of apelin expression regulation by the synthetic retinoid Am80 in VSMCs. The results showed that Am80 markedly up-regulated apelin mRNA and protein levels in VSMCs. Furthermore, KLF5 (Krüppel-like factor 5) and Sp1 (stimulating protein-1) co-operatively mediated Am80-induced apelin expression through their direct binding to the TCE (transforming growth factor-β control element) on the apelin promoter. Interestingly, upon Am80 stimulation, the RARα (retinoic acid receptor α) was recruited to the apelin promoter by interacting with KLF5 and Sp1 prebound to the TCE site of the apelin promoter to form a transcriptional activation complex, subsequently leading to the up-regulation of apelin expression in VSMCs. An in vivo study indicated that Am80 increased apelin expression in balloon-injured arteries of rats, consistent with the results from the cultured VSMCs. Thus the results of the present study describe a novel mechanism of apelin regulation by Am80 and further expand the network of RARα in the retinoid pathway.

Optical properties and electronic structures of VO2 films obtained by magnetron sputtering method on quartz and sapphire substrates were analyzed by transmission spectrum and spectroscopic ellipsometry (SE). The metal-to-insulator transition (MIT) characteristics of the two thin films were compared and discussed correlating with their structural details. By fitting spectroscopic ellipsometric data, the dielectric functions, electronic transitions, and optical bandgap of VO2 films can be tuned by substrate effects. On quartz substrate, the VO2 film exhibits a lower transition temperature and broader thermal hysteresis (ΔH). It is found that the lowest order transition (E1) on quartz substrate does not reduce to zero in the metallic phase as expected. There are two reasons: one is the slight decrease in the filled a1g bands compared to the bands due to a greater compressive stress in the quartz films; the other is associated with the donor level (ED) and acceptor level (EA).

A numerical procedure for the evaluation of equivalent permeability tensor for fractured vuggy porous media is presented. At first we proposed a new conceptual model, i.e., discrete fracture-vug network model, to model the realistic fluid flow in fractured vuggy porous medium on fine scale. This new model consists of three systems: rock matrix system, fractures system, and vugs system. The fractures and vugs are embedded in porous rock, and the isolated vugs could be connected via discrete fracture network. The flow in porous rock and fractures follows Darcy’s law, and the vugs system is free fluid region. Based on two-scale homogenization theory, we obtained an equivalent macroscopic Darcy’s law on coarse scale from fine-scale discrete fracture-vug network model. A finite element numerical formulation for homogenization equations is developed. The method is verified through application to a periodic model problem and then is applied to the calculation of equivalent permeability tensor of porous media with complex fracture-vug networks. The applicability and validity of the method for these more general fractured vuggy systems are assessed through a simple test of the coarse-scale model.

Modeling and numerical simulations of fractured vuggy porous media is a challenging problem due to the presence of cavities called macro vugs which are connected via discrete fractures networks. The main difficulty is the co-existence of porous and free-flow region in such media on macro scale. In this study, a novel conceptual discontinuum model i.e. discrete fracture-vug network (DFVN) model has been proposed to this problem. In DFVN conceptual model, naturally fractured vuggy porous rock masses are considered as a composite porous material, consisting of (1) macro fractures system, (2) porous rock matrix system, and (3) macro vugs system. Macro fractures and vugs are embedded in porous rock, and the isolated vugs are connected via discrete fracture network. We model the fractured vuggy media on macroscopic scale using Navier-Stokes equations within the vugular region, Darcy's law within the porous flow region including porous rock matrix system and macro fractures system, and a Beavers-Joseph-Saffman boundary on the interface between two regions. A standard Galerkin finite element method is implemetated for the solution of DFVN model. A good match with analytical and numerical solutions for Poiseuille flow in a free/porous channel was achieved, which verified the accuracy of our finite element numerical scheme. Both 2D DFVN models with homogeneous isotropic rock matrix and heterogeneous anisotropic rock matrix are simulated and studied. The numerical results have shown that DFVN model provides a natural way of modeling realistic fluid flow in fractured vuggy porous media.