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Nucleos(t)ide analogs (NAs) are widely used in the treatment of hepatitis B virus (HBV) and human immunodeficiency virus (HIV). The mutation L210W of HIV-1 reverse transcriptase (RT) is one of the six principal mutations which confer in vivo resistance to zidovudine. Due to the similar 3D-structure and high conservation between HIV-RT and HBV-RT, the present study aimed to clarify whether corresponding mutations in HBV may decrease its susceptibility to relevant NAs. Mutations including rtL228C/W, rtL229W and rtL228W/L229W were introduced into a HBV replication competent plasmid by fusion polymerase chain reaction. Replication capacity, HBs/e antigen (Ag) levels and susceptibility to NAs were subsequently analyzed in vitro. Single or combination mutations of rtL228 and rtL229 impaired HBV replication. Decreased HBsAg secretion in the supernatant and production in the cell lysate wasobserved with single rtL229W or in combination with rtL228W, while there was no significant difference between wild-type and mutant HBV with regard to the level of HBeAg in the supernatant and susceptibility to commonly-used NAs. Substitution mutations of rtL228 and/or L229 in HBV did not alter the susceptibility of the virus to NAs, although replication and HBsAg secretion were affected. [ABSTRACT FROM AUTHOR]

Shikonin and its derivatives are the main active components in the medicinal plant Arnebia euchroma and possess extensive pharmaceutical properties. In this study, we developed an optimized yeast system to obtain high-level production of 3-geranyl-4-hydroxybenzoate acid (GBA), an important intermediate involved in shikonin biosynthesis pathway. For host selection, recombinant expression of p-hydroxybenzoate:geranyltransferase (PGT) derived from A. euchroma was performed in Saccharomyces cerevisiae WAT11U strain and high yield monoterpene strain. In shake flask culture with 1 mM p-hydroxybenzoate acid (PHBA), they could yield GBA at 0.1567 and 20.8624 mg L-1, respectively. Additionally, AePGT6 showed higher enzymatic activity than its homologs. Moreover, by combining improvement in the homologous mevalonate pathway with reconstruction in the heterologous shikimic pathway, a de novo GBA synthesis pathway was constructed in StHP6tHC with co-overexpressed SctHMG1, optimized EcUbiC and AePGT6. A high titer of 179.29 mg L-1 GBA was achieved in StHP6tHC under shake flask fermentation with 1 mM PHBA. These results suggest that yeast could be engineered systematically to enable an efficient monoterpene-quinone or naphthoquinone production. [ABSTRACT FROM AUTHOR]

In this paper, an experimental study on exploding a copper wire in air, water, incombustible powders, and energetic materials is performed. We examined the effects of the surrounding media on the explosion process and its related phenomena. Experiments were first carried out with copper wire explosions driven by microsecond timescale pulsed currents in air, water and the half-half case. Then, the copper wires were exploded in air, water, SiO2 powders, quartz sand, NaCl powders, and energetic-material cylinders, respectively. Our experimental results indicated that the explosion process was significantly influenced by the surrounding media, resulting in noticeable differences in energy deposition, optical emission and shock waves. In particular, incombustible powders could throttle the current flow completely when a fine wire was adopted. We also found that an air or incombustible-powder layer could drastically attenuate the shock wave generated by a wire explosion. As for energetic-material loads, obvious discrepancies were found in voltage/current waveforms from vaporization when compared with a wire explosion in air/water, which meant the metal vapor/liquid drops play a significant role in the ignition process. [ABSTRACT FROM AUTHOR]

A platform SWE-2 used for single wire explosion experiments has been designed, established, and commissioned. This paper describes the design and initial experiments of SWE-2. In summary, two pulsed current sources based on pulse capacitors and spark gaps are adopted to drive sub-microsecond and microsecond time scale wire explosions in a gaseous/liquid medium, respectively. In the initial experiments, a single copper wire was exploded in air, helium, and argon with a 0.1-0.3 MPa ambient pressure as well as tap water with a 283-323 K temperature, 184-11 000 μS/cm conductivity, or 0.1-0.9 MPa hydrostatic pressure. In addition, the diagnostic system is introduced in detail. Energy deposition, optical emission, and shock wave characteristics are briefly discussed based on experimental results. The platform was demonstrated to operate successfully with a single wire load. These results provide the potential for further applications of this platform, such as plasmamatter interactions, shock wave effects, and reservoir simulations. [ABSTRACT FROM AUTHOR]

Atmospheric pressure glow discharge (APGD) has been widely used in the industrial field. The industrial applications are based on achieving stable and diffusive APGD in a relatively large space. The existing sources only achieved stable and diffusive APGD between a short inter-electrode distance within 5 millimeters. In this paper, the effect of a transverse stationary magnetic field on the diffusion of filamentary APGD was studied in a pin-to-ring coaxial gap. The APGD was driven by a high-voltage resonant power supply, and the stationary magnetic field was supplied by a permanent magnet. The stable and diffusive APGD was achieved in the circular area, which diameter was 20 millimeters. The experimental results revealed that more collision ionization occurred and the plasma was distributed diffusively in the discharge gap by applying the external transverse magnetic field. Besides, it is likely to obtain more stable and diffusive APGD in the coaxial pin-to-ring discharge gap when adjusting the input voltage, transverse magnetic flux density and resonant frequency of the power supply. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD); however, no clinically approved vaccine or antiviral treatment is currently available for EV71 infection. In the present study, a murine model of EV71 infection was constructed. The clinical isolates of EV71 were amplified in Vero cells and used to challenge adult mice via hydrodynamic injection (HI) and intraperitoneal injection (IP). Following two challenges, >50% of the mice succumbed to EV71 infection. Surviving female mice were identified to have impaired fertility and their litter sizes were significantly decreased compared with the control group. The antibody against EV71-VP1 persisted in the sera of female mice at a high titer for >2 years after challenge. The maternal antibody in the offspring sera also persisted for ~1 year and disappeared after ~2 years. Results from the present study suggest that a high titer of active EV71 was able to impair the reproductivity of adult female mice, and that high levels of maternal antibody persisted in the offspring and protected postnatal mice from EV71-induced mortality. The promising antigenicity, immunogenicity and reactogenicity of EV71 suggests that it a potential vaccine target that may be beneficial to the control of HFMD, through immunizing infants and women of reproductive age. [ABSTRACT FROM AUTHOR]

• An energy optimization management model for adaptive control of cooling, heating and electric peak load in coastal residential areas is presented. • The charging power of electric vehicle and the controllable power of air conditioner, water heater and refrigerator are coordinated for peak load control. • The coupling relationship and storage coordination of cooling, heating and electric energy is used to enhance the optimal control of peak load. • The deep Q-learning algorithm is used to solve the energy management optimization problem of coastal residential area for peak load control with good results. Aiming at the coastal residential area, considering the natural characteristics of wind and photovoltaic energy, the supply characteristics of gas and electric energy, the energy consumption law of cold, heat and electricity and the complementary and coupling relationship of various energy sources and load, this paper studies the formation conditions and various scenarios of peak load in the residential area with CCHP systems. Using the regulation characteristics of controllable loads such as electric vehicle, air conditioner, water heater and refrigerator, considering the coordination of cooling, heating and electric energy storage, the interchangeability and controllability of air conditioner based on electric/gas energy, and the transferability, interchangeability and controllability of water heater based on electric/gas/solar/heat energy, A collaborative energy management model for coastal resident area with electricity, gas, wind and solar energy is presented for peak load adaptive control of cooling, heating and electric energy. The Q-learning algorithm is used to solve the energy management optimization problem of peak load control in coastal residential areas, and good results are achieved, such as effectively reducing load fluctuations, improving the economy of the system, and increasing the self-sufficiency of the system. [ABSTRACT FROM AUTHOR]

BACKGROUND: The potential carcinogenicity of naphthalene (NA), a ubiquitous environmental pollutant, in human respiratory tract is a subject of intense debate. Chief among the uncertainties in risk assessment for NA is whether human lung CYP2A13 and CYP2F1 can mediate NA's respiratory tract toxicity. OBJECTIVES: We aimed to assess the in vivo function of CYP2A13 and CYP2F1 in NA bioactivation and NA-induced respiratory tract toxicity in mouse models. METHODS: Rates of microsomal NA bioactivation and the effects of an anti-CYP2A antibody were determined for lung and nasal olfactory mucosa (OM) from Cyp2abfgs-null, CYP2A13-humanized, and CYP2A13/2F1-humanized mice. The extent of NA respiratory toxicity was compared among wild-type, Cyp2abfgs-null, and CYP2A13/2F1-humanized mice following inhalation exposure at an occupationally relevant dose (10 ppm for 4 hr). RESULTS: In vitro studies indicated that the NA bioactivation activities in OM and lung of the CYP2A13/2F1-humanized mice were primarily contributed by, respectively, CYP2A13 and CYP2F1. CYP2A13/2F1-humanized mice showed greater sensitivity to NA than Cyp2abfgs-null mice, with greater depletion of nonprotein sulfhydryl and occurrence of cytotoxicity (observable by routine histology) in the OM, at 2 or 20 hr after termination of NA exposure, in humanized mice. Focal, rather than gross, lung toxicity was observed in Cyp2abfgs-null and CYP2A13/2F1-humanized mice; however, the extent of NA-induced lung injury (shown as volume fraction of damaged cells) was significantly greater in the terminal bronchioles of CYP2A13/2F1-humanized mice than in Cyp2abfgs-null mice. CONCLUSION: CYP2F1 is an active enzyme. Both CYP2A13 and CYP2F1 are active toward NA in the CYP2A13/2F1-humanized mice, where they play significant roles in NA-induced respiratory tract toxicity. [ABSTRACT FROM AUTHOR]

Canna yellow mottle virus (CaYMV) is an important badnavirus infecting Canna spp. worldwide. This is the first report of CaYMV in flowering ginger (Alpinia purpurata) in Hawaii, where it is associated with yellow mottling and necrosis of leaves, vein streaking, and stunted plants. We have sequenced CaYMV in A. purpurata (CaYMV-Ap) using a combination of next-generation sequencing and traditional Sanger sequencing techniques. The complete genome of CaYMV-Ap was 7,120 bp with an organization typical of other Badnavirus species. Our results indicated that CaYMV-Ap was present in the episomal form in infected flowering ginger. We determined that this virus disease is prevalent in Hawaii and could potentially have significant economic impact on the marketing of A. purpurata as cut flowers. There is a potential concern that the host range of CaYMV-Ap may expand to include other important tropical plants. [ABSTRACT FROM AUTHOR]

Background/Objectives: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs). Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT) was identified by confocal microscopy. Right ventricular systolic pressure (RVSP) was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH) was determined by weighing the cardiac muscle. Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH. Conclusion: Rev produced a beneficial effect partially by enhancing the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel future strategy for the treatment of PAH. [ABSTRACT FROM AUTHOR]

Purpose: To determine the chemical components of the essential oil of Elsholtizia dense in Sichuan Province and evaluate the effect of the oil on human hepatoma cells (SMMC-7721) in vitro. Methods: The essential oil was extracted using the modified steam-distillation extraction method, and its chemical components were determined by gas chromatography-mass spectrometry (GC-MS). The effect of the essential oil on proliferation of SMMC-7721 cells was studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, with L02 and HeLa cells serving as control groups. Results: GC-MS results show that the essential oil of E. dense contains 40 components. Thirty seven components were identified and accounted for 98.39% of the essential oil. The two main components were rosefuran epoxide (53.12%) and 2-ethyl imidazole (29.8%). The oil significantly inhibited cell proliferation in a concentration- and time-dependent manner (p < 0.05). SMMC-7721 cells were more inhibited than L02 and HeLa cells by the oil, with half maximal inhibitory concentration (IC50) values of 26.23 and 25.46 µg/mL after 8-h and 24-h treatments, respectively. Conclusion: Out of the 40 chemical components of the essential oil of E. dense, rosefuran epoxide and 2-ethyl imidazole were the most abundant. The oil has a significant anti-tumor effect on SMMC-7721 cells, and thus has a potential to be developed as an anti-liver cancer drug. [ABSTRACT FROM AUTHOR]

The serine/threonine kinase Unc-51-like kinase-1 (Ulk1) is thought to be essential for induction of autophagy, an intracellular bulk degradation process that is activated by various stresses. Although several proteins have been suggested as Ulk1 substrates during autophagic process, it still remains largely unknown about Ulk1's physiological substrates. Here, by performing in vitro and in vivo phosphorylation assay, we report that the co-chaperone cell division cycle protein 37 (Cdc37) is a Ulk1 substrate. Ulk1-mediated phosphorylation of Ser-339 in Cdc37 compromised the recruitment of client kinases to a complex comprising Cdc37 and heat shock protein 90 (Hsp90) but only modestly affected Cdc37 binding to Hsp90. Because the recruitment of protein kinase clients to the Hsp90 complex is essential for their stability and functions, Ser-339 phosphorylation of Cdc37 disrupts its ability as a co-chaperone to coordinate Hsp90. Hsp90 inhibitors are cancer chemotherapeutic agents by inducing depletion of clients, many of which are oncogenes. Upon treatment with an Hsp90 inhibitor in cancer cells, Ulk1 promoted the degradation of Hsp90-Cdc37 client kinases, resulting in increased cellular sensitivity to Hsp90 inhibitors. Thus, our study provides evidence for an anti-proliferative role of Ulk1 in response to Hsp90 inhibition in cancer cells. [ABSTRACT FROM AUTHOR]

Microscopic understanding of interaction between H2O and MAPbI3 (CH3NH3PbI3) is essential to further improve efficiency and stability of perovskite solar cells. A complete picture of perovskite from initial physical uptake of water molecules to final chemical transition to its monohydrate MAPbI3·H2O is obtained with in situ infrared spectroscopy, mass monitoring, and X-ray diffraction. Despite strong affinity of MA to water, MAPbI3 absorbs almost no water from ambient air. Water molecules penetrate the perovskite lattice and share the space with MA up to one H2O per MA at high-humidity levels. However, the interaction between MA and H2O through hydrogen bonding is not established until the phase transition to monohydrate where H2O and MA are locked to each other. This lack of interaction in water-infiltrated perovskite is a result of dynamic orientational disorder imposed by tetragonal lattice symmetry. The apparent inertness of H2O along with high stability of perovskite in an ambient environment provides a solid foundation for its long-term application in solar cells and optoelectronic devices. [ABSTRACT FROM AUTHOR]

This study investigated the biodiversity, phylogeny, and antifungal activity of endophytic fungi isolated from Zanthoxylum bungeanum. A total of 940 isolates obtained were grouped into 93 morphotypes, 43 species, and 23 genera, which were authenticated by molecular identification based on rDNA internal transcribed spacer (ITS) sequence analysis. A high diversity of endophytic fungi from Z. bungeanum are observed with high species richness S (43), Margalef index D0 (6.1351), Shannon-Wiener index H0 (3.2743), Simpson diversity index Ds (0.9476), PIE index (0.9486), and evenness Pielou index J (0.8705) but a low dominant index l (0.0524). Significant tissue specificity of the endophytic fungi was observed in Z. bungeanum, and the highest species richness and diversity indexes were obtained in the stem. Phylogenetic analyses of the 93 endophytic isolates were carried out by the neighbor-joining (NJ) method to demonstrate their evolutionary processes. Antifungal activities of endophytic fungi were assayed and eight endophytic isolates showed strong and long-lasting inhibition against host pathogenic fungi Fusarium sambucinum and Pseudocercospora zanthoxyli. Here, for the first time, we systematically demonstrate the biodiversity, phylogeny, and antifungal activity of endophytic fungi associated with Z. bungeanum and reveal the value of sampling different tissues of a given plant to obtain the greatest endophyte species diversity, which might offer a framework for further investigation and utilization of endophytic fungi as aunique source of interesting and useful bioactive compounds. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential of Lonicera macranthoides Hand. -Mazz. Yulei1 suspension culture system for enhanced production of the main secondary metabolite, chlorogenic acid. Methods: The callus of L. macranthoides Hand.-Mazz. "Yulei1" was suspension cultured in B5 liquid medium supplemented with different plant growth regulators. Biomass accumulation was calculated by weight method and chlorogenic acid production was measured using high performance liquid chromatography (HPLC). HPLC was carried out on C18 analytical column at 35 °C and the detection wavelength was set at 324 nm. Results: The results showed that maximum accumulation of biomass and chlorogenic acid were achieved 15 days after culture growth. The optimized conditions for biomass accumulation and chlorogenic acid production were 50 g/L of inoculum on fresh weight basis, B5 medium supplemented with plant growth regulators, 30 - 40 g/L sucrose and initial medium pH of 5.5. Maximum accumulation of chlorogenic acid and biomass were observed when the culture medium was supplemented with 2.0 mg/L6-BA. Optimal accumulation of chlorogenic acid was observed using combination of hormones 2.0 mg/L 6-Benzyladenine (BA) + 0.5 mg/L2, 4-Dichlorophenoxyacetic acid (2,4-D), while optimal accumulation of biomass was observed with 2.0 mg/L 6-BA + 2.0 mg/L2, 4-D. In addition, phenylalanine also contributed to the synthesis of chlorogenic acid at a concentration > 50 mg/L. Conclusion: Cell suspension cultures of L. macranthoides Hand.-Mazz. "Yulei1" have successfully been established. The findings provide a potential basis for large scale production of chlorogenic acid using cell suspension cultures of L. macranthoides. [ABSTRACT FROM AUTHOR]

The first example of decarboxylative difluoroacetamidation of aα,β-unsaturated carboxylic acids by using difluoromethyl-substituted carbonyl compounds was disclosed. The procedure, which was mediated by low-cost and benign CuSO4, furnished a broad range of difluorinated alkenes in remarkable yields with only the E configuration in most of the cases. Moreover, the product could be smoothly transformed to the corresponding difluorofunctionalized ester and alcohol in high yields. [ABSTRACT FROM AUTHOR]

Background: Sperm-associated antigen 9 (SPAG9) is upregulated in several malignancies and its overexpression is positively correlated with cancer cell malignancies. However, the specific biological roles of SPAG9 in hepatocellular carcinoma (HCC) are less understood. Methods: We analyzed SPAG9 and ETS-like gene 1, tyrosine kinase (ELK1) expression in 50 paired HCC specimens and adjacent noncancerous liver specimens using immunohistochemistry. SPAG9 small interfering RNA (siRNA) was used to knockdown SPAG9 expression in HCCLM3 and HuH7 cell lines. We used plasmids to upregulate ELK1 expression and siRNA to downregulate ELK1 expression in HuH7 cells. Quantitative real-time polymerase chain reaction and Western blot were used to evaluate the expression of SPAG9 and ELK1 at the mRNA and protein level, respectively. Wound healing, matrigel migration, and invasion analyses were performed to determine the effect of SPAG9 and ELK1 on HCC metastasis. Results: SPAG9 and ELK1 were overexpressed in HCC tissue specimens and their expressions were higher in HCCLM3 and HuH7 cells compared to the low-metastatic HepG2 cells. Overexpression of SPAG9 was positively associated with tumor-node-metastasis staging (P=0.032), metastasis parameters (P=0.018) of HCC patients, and ELK1 expression (r=0.422, P<0.001) in HCC tissue specimens. In addition, knockdown of SPAG9 in HCCLM3 and HuH7 cells using siRNA significantly suppressed cell migration and invasion. Furthermore, we observed inhibition of ELK1 expression and p38 signaling. However, ELK1 overexpression reversed the inhibitory effects of SPAG9 siRNA on HCC cell metastasis and ELK1 depletion inhibited HuH7 cell migration and invasion. Conclusion: SPAG9 overexpression was positively correlated with HCC metastasis and SPAG9-induced migration and invasion were partially dependent on ELK1 expression in HCC cell lines. These results suggest that SPAG9 may be a potential anti-metastasis target effective in HCC therapy. [ABSTRACT FROM AUTHOR]

We investigate the electronic structure and photoexcitation dynamics of alkali atoms (Rb and Cs) chemisorbed on transition-metal Ru(0001) single-crystal surface by angle- and time-resolved multiphoton photoemission. Three- and four-photon photoemission (3PP and 4PP) spectroscopic features due to the a and n resonances arising from the ns and np states of free alkali atoms are observed from ~ 2 eV below the vacuum level in the zero-coverage limit. As the alkali coverage is increased to a maximum of 0.02 monolayers, the resonances are stabilized by formation of a surface dipole layer, but in contrast to alkali chemisorption on noble metals, both resonances form dispersive bands with nearly free-electron mass. Density functional theory calculations attribute the band formation to substrate-mediated interaction involving hybridization with the unoccupied d bands of the substrate. Time-resolved measurements quantify the phase and population relaxation times in the three-photon photoemission (3PP) process via the σ and π resonances. Differences between alkali-atom chemisorption on noble and transition metals are discussed. [ABSTRACT FROM AUTHOR]

Based on the operational regional ensemble prediction system (REPS) in China Meteorological Administration (CMA), this paper carried out comparison of two initial condition perturbation methods: an ensemble transform Kalman filter (ETKF) and a dynamical downscaling of global ensemble perturbations. One month consecutive tests are implemented to evaluate the performance of both methods in the operational REPS environment. The perturbation characteristics are analyzed and ensemble forecast verifications are conducted; furthermore, a TC case is investigated. The main conclusions are as follows: the ETKF perturbations contain more power at small scales while the ones derived from downscaling contain more power at large scales, and the relative difference of the two types of perturbations on scales become smaller with forecast lead time. The growth of downscaling perturbations is more remarkable, and the downscaling perturbations have larger magnitude than ETKF perturbations at all forecast lead times. However, the ETKF perturbation variance can represent the forecast error variance better than downscaling. Ensemble forecast verification shows slightly higher skill of downscaling ensemble over ETKF ensemble. A TC case study indicates that the overall performance of the two systems are quite similar despite the slightly smaller error of DOWN ensemble than ETKF ensemble at long range forecast lead times. [ABSTRACT FROM AUTHOR]

Background: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. Methods: EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. Results: When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c +mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. Conclusions: During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts. [ABSTRACT FROM AUTHOR]

Background: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. Methods: EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. Results: When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c +mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. Conclusions: During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts. [ABSTRACT FROM AUTHOR]

In this study, we investigate the relationship of hepatitis B virus (HBV) infection and autophagy. HepG2 cells and HepG2 cells infected with HBV (HepG2.2.15) were transfected with GFP-LC3 (green fluorescence protein conjugated with microtubule-associated protein 1 light chain 3) expression vector and autophagy status was then examined with confocal microscope. HepG2.2.15 cells were further treated with serum-free medium or 3-methyladenine (3-MA), and subjected to Hepatitis B core antigen (HBcAg), Hepatitis B surface antigen (HBsAg), or hepatitis B polymerase protein detection by immunohistochemistry. Localization of the GFP-LC3 and the HBV proteins was observed by confocal fluorescence microscope. The level of SQSTM1/p62 protein was also evaluated by Western blot analysis. In contrast to a diffuse distribution in HepG2 cells, GFP-LC3 formed distinct punctate dots, which were further enhanced by nutritional starvation, in HepG2.2.15 cells. The expression of hepatitis B polymerase and HBcAg, but not HBsAg, was positively correlated with the autophagic intensity. However, no co-localizations were observed between HBV proteins and autophagosomes. Suppression of autophagy reduced the expression of hepatitis B polymerase and HBcAg, but not HBsAg. Western blot showed that SQSTM1/p62 protein level was declined in HepG2.2.15 cells comparing HepG2 cells, and further reduced while upon serum starvation. In conclusion, HBV infection induces autophagic degradation and autophagy. Autophagy is critical for HBV replication. However HBV replication does not take place in autophagosomes. [ABSTRACT FROM AUTHOR]

Macrophage markers in skeletal muscle of obese subjects are elevated and inversely relate to insulin sensitivity. The present study aimed to investigate whether short-term high-fat high-calorie (HFHC) diet already increases macrophage markers and affects glucose metabolism in skeletal muscle of healthy lean subjects. Muscle biopsies were obtained from 24 healthy lean young men before and after a 5-day HFHC-diet. mRNA expression levels of relevant genes in muscle and glucose, insulin, C-peptide and cholesteryl ester transfer protein (CETP) levels in plasma were measured. In addition, we assessed hepatic triacylglycerol ('triglyceride') (HTG) content by magnetic resonance spectroscopy and subcutaneous white adipose tissue (sWAT) biopsies were analysed histologically from a subset of subjects (n=8). A 5-day HFHC-diet markedly increased skeletal muscle mRNA expression of the general macrophage markers CD68 (3.7-fold, P<0.01) and CD14 (3.2-fold, P<0.01), as well as the M1 macrophage markers MARCO (11.2-fold, P<0.05), CD11c (1.8-fold, P<0.05) and MRC1 (1.7-fold, P<0.05). This was accompanied by down-regulation of SLC2A4 and GYS1 mRNA expression, and elevated plasma glucose (+4%, P<0.001) and insulin (+55%, P<0.001) levels together with homoeostasis model assessment of insulin resistance (HOMA-IR) (+48%, P<0.001), suggesting development of insulin resistance (IR). Furthermore, the HFHC-diet markedly increased HTG (+118%, P<0.001) and plasma CETP levels (+21%, P<0.001), a marker of liver macrophage content, whereas sWAT macrophage content remained unchanged. In conclusion, short-term HFHC-diet increases expression of macrophage markers in skeletal muscle of healthy men accompanied by reduced markers of insulin signalling and development of IR. Therefore, recruitment of macrophages into muscle may be an early event in development of IR in response to short-term HFHC-feeding. [ABSTRACT FROM AUTHOR]

Lipoproteins can induce complement activation resulting in opsonization and binding of these complexes to complement receptors. We investigated the binding of opsonized native LDL and acetylated LDL (acLDL) to the complement receptor 1 (CR1). Binding of complement factors C3b, IgM, C1q, mannose-binding lectin (MBL), and properdin to LDL and acLDL were investigated by ELISA. Subsequent binding of opsonized LDL and acLDL to CR1 on CR1-transfected Chinese Hamster Ovarian cells (CHO-CR1) was tested by flow cytometry. Both native LDL and acLDL induced complement activation with subsequent C3b opsonization upon incubation with normal human serum. Opsonized LDL and acLDL bound to CR1. Binding to CHO-CR1 was reduced by EDTA, whereas MgEGTA only reduced the binding of opsonized LDL, but not of acLDL suggesting involvement of the alternative pathway in the binding of acLDL to CR1. In vitro incubations showed that LDL bound C1q, whereas acLDL bound to C1q, IgM, and properdin. MBL did neither bind to LDL nor to acLDL. The relevance of these findings was demonstrated by the fact that ex vivo up-regulation of CR1 on leukocytes was accompanied by a concomitant increased binding of apolipoprotein B-containing lipoproteins to leukocytes without changes in LDL-receptor expression. In conclusion, CR1 is able to bind opsonized native LDL and acLDL. Binding of LDL to CR1 is mediated via the classical pathway, whereas binding of acLDL is mediated via both the classical and alternative pathways. Binding of lipoproteins to CR1 may be of clinical relevance due to the ubiquitous cellular distribution of CR1. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin (mTOR) integrates multiple extracellular and intracellular signals to regulate cell growth and survival. Hyperactivation of mTOR has been observed in various cancers. Regulation of mTOR activity is thus of importance in physiological processes and tumor development. Here, we present pyruvate dehydrogenase kinase 4 (PDK4) as a novel regulator of mTORC1 signaling. mTORC1 activity was augmented with PDK4 overexpression and reduced by PDK4 suppression in various cell lines. Furthermore, PDK4 bound to cAMP-response element-binding protein (CREB) and prevented its degradation. The enhanced CREB consequently transactivated the expression of Ras homolog enriched in brain (RHEB), a direct key activator of mTORC1, independent of AMP-activated protein kinase or tuberous sclerosis complex protein 2. PDK4 potentiated the mTORC1 effectors hypoxiainducible factor 1α and pyruvate kinase isozymes M2 and promoted aerobic glycolysis (Warburg effect). Knockdown ofPDK4 suppressed the tumor development of cancer cells with activated mTORC1. The abundance of PDK4 dictated the responsiveness of cells to the mTOR inhibitor, rapamycin. Combinatory suppression of mTOR and PDK4 exerted synergistic inhibition on cancer cell proliferation. Therefore, PDK4 promotes tumorigenesis through activation of the CREB-RHEBmTORC1 signaling cascade. [ABSTRACT FROM AUTHOR]

The promising endoscopic resection techniques for upper gastrointestinal submucosal tumors (SMTs) are challenged when performed in the gastric fundus. Here, we report on the development of a transcardiac endoscopic tunneling technique (TCTT) for the resection of tumors in this area. A total of 18 patients with gastric fundus SMTs arising from the muscularis propria on endoscopic ultrasound underwent TCTT. The procedure involved the excavation of a submucosal tunnel from the esophagus, through the cardia, to the gastric SMT for resection. The tunnel was closed by clips after retrieval of the tumor. The mean tumor size was 2.1cm (range 0.8-5.0 cm). The mean procedure time was 75.1 minutes (range 40-100 minutes). Complete resection was achieved in all cases. Iatrogenic perforation occurred in one case. This and one other patient developed mild pneumoperitoneum on the day after the procedure; symptoms resolved under conservative management. No patient developed gastrointestinal leakage, delayed bleeding, or secondary infection. Therefore, in this pilot study, TCTT provided a definitive histological diagnosis as well as a feasible, safe, and easy therapeutic approach for gastric fundus SMTs arising from muscularis propria in the circular area within 8cmbelow the cardia. [ABSTRACT FROM AUTHOR]

Cervical cancer is still one of the leading causes of cancer deaths in women worldwide, especially in the developing countries. It is a major metabolic character of cancer cells to consume large quantities of glucose and derive more energy by glycolysis even in the presence of adequate oxygen, which is called Warburg effect that can be exaggerated by hypoxia. The high risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. Hypoxia-inducible factor 1α (HIF-1α), a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth, is highly increased by HPV E6. HIF-1α is a best-known target of the von Hippel-Lindau tumor suppressor (VHL) as an E3 ligase for degradation. In the present work, we found that HPV16 E6 promotes hypoxia induced Warburg effect through hindering the association of HIF-1α and VHL. This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation. These results suggest that oncoprotein E6 plays a major role in the regulation of Warburg effect and can be a valuable therapeutic target for HPV-related cancer. [ABSTRACT FROM AUTHOR]

When an object is placed on a water surface, the air-water interface deforms and a meniscus arises due to surface tension effects, which in turn produces a lift force or drag force on the partly submerged object. This study aims to investigate the underlyingmechanism of the vertical force acting on spindly cylinders in contact with a water surface. A simplified 2-D model is presented, and the profile of the curved air-water interface and the vertical force are computed using a numerical method. A parametric study is performed to determine the effects of the cylinder center distance, inclined angle, static contact angle, and radius on the vertical force. Several key conclusions are derived from the study: (1) Although the lift force increases with the cylinder center distance, cylinders with smaller center distances can penetrate deeper belowthewater surface before sinking, thereby obtaining a larger maximum lift force; (2) An increase in the inclined angle reduces the lift force, which can enable the lower cylinders fall more deeply before sinking; (3)While the effect of static contact angle is limited for angles greater than 90?, hydrophobicity allows cylinders to obtain a larger lift force and load capacity on water; (4) The lift force increases rapidly with cylinder radius, but an increase in radius also increases the overall size and weight of cylinders and decreases the proportion of the surface tension force. These findings may prove helpful in the design of supporting legs of biologically-inspired miniature aquatic devices, such as water strider robots. [ABSTRACT FROM AUTHOR]

Long-period stacking ordered (LPSO) phases play an essential role in the development of magnesium alloys because they have a direct effect on mechanical and corrosion properties of the alloys. The LPSO structures are mostly divided to 18R and 14H. However, to date there are no consistent opinions about their degradation properties although both of them can improve mechanical properties. Herein we have successfully obtained two LPSO phases separately in the same Mg-Dy-Zn system and comparatively investigated the effect of different LPSO phases on degradation behavior in 0.9 wt.% NaCl solution. Our results demonstrate that a fine metastable 14H-LPSO phase in grain interior is more effective to improve corrosion resistance due to the presence of a homogeneous oxidation film and rapid film remediation ability. The outstanding corrosion resistant Mg-Dy-Zn based alloys with a metastable 14H-LPSO phase, coupled with low toxicity of alloying elements, are highly desirable in the design of novel Mg-based biomaterials, opening up a new avenue in the area of bio-Mg. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study describing the use of placenta slice culture and Ussing chamber for the development of an in vitro model of the human placental barrier. The authors mentioned the presence of syncytiotrophoblast cells with several endoplasmic reticulum and mitochondria covered with a dense microvillus in the placenta slice. The ß-human chorionic gonadotropin levels, mRNA, and fluorescent market permeability in the Ussing chamber and placenta slice are cited.

An eddy covariance system and other atmospheric and oceanic parameters were measured simultaneously from a fixed Platform-A in the Bohai Gulf during early mid-August 2011. One of the main goals of the comprehensive observation was to reveal the basic meteorological and hydrological characteristics of the Bohai Gulf. The results indicated that the diurnal characteristic curve for the air temperature (AT) was steeply unimodal, while the curve of the SST was a bimodal valley type and mainly influenced by tides with its valley value corresponding to the high water level during the observation period. Southeasterly winds dominated and the wind speed was generally lower than 8 m/s, and the atmospheric stability over the Bohai Gulf was generally unstable. The wave strength levels were generally below level 3, with a greater number of swell waves than wind waves. The latter were usually associated with more momentum transport, a larger difference between AT and SST, and less heat transport. During the observational period, the mean momentum, sensible, and latent heat turbulent fluxes were 0.21, 21.6, and 27.8W/m2, respectively. The ratio of the mean latent and sensible turbulent fluxes was about 1.3 and much lower than that in the South China Sea during the summer. [ABSTRACT FROM AUTHOR]

In fish immunity, the regulatory role of transforming growth factor-b1 (TGF-b1) has not been fully characterized. Here we examined the immunoregulatory effects of TGF-b1 in grass carp peripheral blood leukocytes (PBL) and head kidney leukocytes (HKL). It is interesting that TGF-b1 consistently stimulated the cell viability and the mRNA levels of proinflammatory cytokines (Tnfa and Ifnc) and T/B cell markers [Cd4-like (Cd4l), Cd8α, Cd8β and Igm] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-α1 type I receptor, activin receptor-like kinase 5 (ALK5), was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes. [ABSTRACT FROM AUTHOR]

To explore environmentally benign solvents for the absorption of NO and NO2, a series of caprolactam tetrabutyl ammonium halide ionic liquids were synthesized. The solubility of NO and NO2 was measured at temperatures ranging from 298.2 to 363.2 K and atmospheric pressure, and the following trend in the solubility of NO and NO2 in ionic liquids with various halide anions was observed, respectively: F > Br > Cl and Br > Cl > F. Moreover, as the temperature increased from 308.15 to 363.15 K and the mole ratio of caprolactam increased from 2:1 to 6:1, the solubility of NO increased. Alternatively, the solubility of NO2 decreased as the temperature increased from 298.15 to 363.15 K, and the mole ratio of caprolactamincreased from 2:1 to 6:1. The absorption and desorption of NO and NO2 was practically reversible in the ionic liquids, which was characterized by nuclear magnetic resonance. The method, which is at least partially reversible, offers interesting possibilities for the removal of NO and NO2. [ABSTRACT FROM AUTHOR]

Although aerobic glycolysis (the Warburg effect) is a hallmark of cancer, key questions, including when, how, and why cancer cells become highly glycolytic, remain less clear. For a largely unknown regulatory mechanism, a rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) isoform is exclusively expressed in embryonic, proliferating, and tumor cells, and plays an essential role in tumor metabolism and growth. Because the receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) signaling cascade is a frequently altered pathway in cancer, we explored its potential role in cancer metabolism. We identified mTOR as a central activator of the Warburg effect by inducing PKM2 and other glycolytic enzymes under normoxic conditions. PKM2 level was augmented in mouse kidney tumors due to deficiency of tuberous sclerosis complex 2 and consequent mTOR activation, and was reduced in human cancer cells by mTOR suppression. mTOR up-regulation of PKM2 expression was through hypoxia-inducible factor 1α (HIF1α)-mediated transcription activation, and c-Myc-heterogeneous nuclear ribonucleoproteins (hnRNPs)-dependent regulation of PKM2 gene splicing. Disruption of PKM2 suppressed oncogenic mTOR-mediated tumorigenesis. Unlike normal cells, mTOR hyperactive cells were more sensitive to inhibition of mTOR or glycolysis. Dual suppression of mTOR and glycolysis synergistically blunted the proliferation and tumor development of mTOR hyperactive cells. Even though aerobic glycolysis is not required for breach of senescence for immortalization and transformation, the frequently deregulated mTOR signaling during multistep oncogenic processes could contribute to the development of the Warburg effect in many cancers. Components of the mTOR/HIF1α/Myc-hnRNPs/PKM2 glycolysis signaling network could be targeted for the treatment of cancer caused by an aberrant RTK/PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Hydrophilic Ti-MCM-41 was modified by alkylsilyl groups using n-octadecyltrichlorosilane as the precursor, yielding an amphiphilic molecular sieve denoted as OTS-Ti-MCM-41. The sample retained mesoporous structure and morphology, as confirmed by XRD, N2 adsorption–desorption, and SEM. The presence of surface alkylsilyl groups was confirmed by infrared spectroscopy. The amphiphilic OTS-Ti-MCM-41 located at the boundary between aqueous and organic phases acted as a phase-boundary catalyst for the photooxidation of dibenzothiophene (DBT) without the need of adding a co-solvent to drive liquid–liquid phase transfer. With H2O2 as the oxidant, the conversion of DBT on OTS-Ti-MCM-41 was up to 98% at 2 h, much higher than that on Ti-MCM-41. When air was used instead of H2O2 as the oxidant, the conversion of DBT on OTS-Ti-MCM-41 was up to 85% at 2 h. Hydrophilic Ti-MCM-41 was modified by alkylsil groups using n-octadecyltrichlorosilane as the precursor. The resulting OTS-Ti-MCM-41 sample located at the boundary between aqueous and organic phases acted as a phase-boundary catalyst for the photooxidation of dibenzothiophene (DBT).[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The article presents information on heptamethine cyanine dyes. Heptamethine cyanine dyes employed as fluorescence labels and sensors of biomolecules in vivo have attracted immense interest because their spectra reach the near-infrared region, where a biological matrix exhibits the least absorption and autofluorescence background. However, most polymethine cyanine dyes have the fatal disadvantage that their Stokes shifts are less than 25 nm. The authors have synthesized two heptamethine cyanine dyes by introducing alkylamino groups at the central position. The new dyes are suggested to be a new paradigm for excited-state ICT. Significantly, they have a large Stokes shift and strong fluorescence which make them more suitable for use as fluorescence probes than do common cyanine dyes.