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In this study, we assessed the potential synergistic effect of the Erns RNase activity and the poly-U insertion in the 39 untranslated region (UTR) of the low-virulence classical swine fever virus (CSFV) isolate Pinar de Rio (PdR) in innate and adaptive immunity regulation and its relationship with classical swine fever (CSF) pathogenesis in pigs. We knocked out the Erns RNase activity of PdR and replaced the long polyuridine sequence of the 39 UTR with 5 uridines found typically at this position, resulting in a double mutant, vPdR-H30K-5U. This mutant induced severe CSF in 5-day-old piglets and 3-week-old pigs, with higher lethality in the newborn (89.5%) than in the older (33.3%) pigs. However, the viremia and viral excretion were surprisingly low, while the virus load was high in the tonsils. Only alpha interferon (IFN-a) and interleukin 12 (IL-12) were highly and consistently elevated in the two groups. Additionally, high IL-8 levels were found in the newborn but not in the older pigs. This points toward a role of these cytokines in the CSF outcome, with age-related differences. The disproportional activation of innate immunity might limit systemic viral spread from the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms. Infection with vPdR-H30K-5U resulted in poor neutralizing antibody responses compared with results obtained previously with the parent and RNase knockout PdR. This study shows for the first time the synergistic effect of the 39 UTR and the Erns RNase function in regulating innate immunity against CSFV, favoring virus replication in target tissue and thus contributing to disease severity. IMPORTANCE CSF is one of the most relevant viral epizootic diseases of swine, with high economic and sanitary impact. Systematic stamping out of infected herds with and without vaccination has permitted regional virus eradication. However, the causative agent, CSFV, persists in certain areas of the world, leading to disease reemergence. Nowadays, low- and moderate-virulence strains that could induce unapparent CSF forms are prevalent, posing a challenge for disease eradication. Here, we show for the first time the synergistic role of lacking the Erns RNase activity and the 39 UTR polyuridine insertion from a low-virulence CSFV isolate in innate immunity disproportional activation. This might limit systemic viral spread to the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms, thus contributing to disease severity. These results highlight the role played by the Erns RNase activity and the 39 UTR in CSFV pathogenesis, providing new perspectives for novel diagnostic tools and vaccine strategies. [ABSTRACT FROM AUTHOR]

Nutrient resorption (NuR) is an important nutrient conservative strategy but little information is available about the effect of nursery fertilization on NuR in the field. In this study, diploid and triploid one-year-old plants of Populus tomentosa Carr. were fertilized with 9 g N per plant, and non-fertilized plants as control. Initial functional attributes, i.e., height, diameter, stem mass, mineral nutrients and non-structural carbohydrate (NSC) levels of each tissue, were measured before planting. Field performance (survival, total height, diameter, stem volume and their growth, leaf nutrient status, and NuR) were measured in the field. Compared to control, 9 g N per plant was benefit for plant growth, mineral nutrients and NSC accumulation of diploids, but declined plant size of triploids before planting. While in the field, fertilization effect on plant size was inversed for each ploidy level. Nursery fertilization increased nitrogen resorption efficiency (NRE) of triploids and decreased phosphorus resorption efficiency (PRE) of both ploidy levels. Initial plant size were the most effective parameters predicting field performance and NuR. Furthermore, NRE was multi-elements controlled as indicated by the correlation of N and P in green and senesced leaves, while PRE was only positively correlated with P in green leaves. However, there was no relationship between field growth and NuR. This study deepened our understanding of NuR from the perspective of artificial managements, for instance nursery fertilization. [ABSTRACT FROM AUTHOR]

With the intensification of market competition, high-tech electronic products need to be constantly updated. The accelerated elimination of outdated products has led to a waste of resources and severe environmental pollution. High-tech electronic enterprises are facing more severe problems than other industries in terms of how to coordinate environmental protection and social responsibility while maintaining their profits, because of the high product elimination rate. However, little research on this aspect exists in previous literature. In this paper, we consider the sustainable development of a high-tech product supply chain from the perspectives of profits, environmental protection efforts and social responsibility costs. Considering the hierarchical structure of the supply chain, a bi-level programming model is constructed under the guidance of the manufacturer. The corresponding hierarchical intelligent algorithm is developed to solve and analyze the model. Based on a sensitivity analysis, key research findings with management significance are obtained, as follows: (1) Compared with a carbon emission penalty strategy, changing the carbon tax exerts a greater impact on the optimal decisions and the manufacturer's and retailer's profits. (2) Social welfare costs have significant impacts on product prices, green innovation expenditure and the leader's profit in a supply chain. (3) Higher retailer carbon abatement costs could help reduce the carbon emissions per unit product. (4) The wholesale price decline rate has a greater impact on product price and manufacturer's environmental protection efforts than the component purchase cost decline rate and selling price decline rate. [ABSTRACT FROM AUTHOR]

Low-virulence classical swine fever virus (CSFV) strains make CSF eradication particularly difficult. Few data are available on the molecular determinants of CSFV virulence. The aim of the present study was to assess a possible role for CSFV virulence of a unique, uninterrupted 36-uridine (poly-U) sequence found in the 3' untranslated region (3' UTR) of the low-virulence CSFV isolate Pinar de Rio (PdR). To this end, a pair of cDNA-derived viruses based on the PdR backbone were generated, one carrying the long poly-U insertion in the 3= UTR (vPdR-36U) and the other harboring the standard 5 uridines at this position (vPdR-5U). Two groups of 20 5-day-old piglets were infected with vPdR-36U and vPdR-5U. Ten contact piglets were added to each group. Disease progression, virus replication, and immune responses were monitored for 5 weeks. The vPdR-5U virus was significantly more virulent than the vPdR-36U virus, with more severe disease, higher mortality, and significantly higher viral loads in serum and body secretions, despite similar replication characteristics in cell culture. The two viruses were transmitted to all contact piglets. Ninety percent of the piglets infected with vPdR-36U seroconverted, while only one vPdR-5U-infected piglet developed antibodies. The vPdR-5U-infected piglets showed only transient alpha interferon (IFN-α) responses in serum after 1 week of infection, while the vPdR-36U-infected piglets showed sustained IFN-α levels during the first 2 weeks. Taken together, these data show that the 3' UTR poly-U insertion acquired by the PdR isolate reduces viral virulence and activates the innate and humoral immune responses without affecting viral transmission. [ABSTRACT FROM AUTHOR]

As the largest developing country in the world, China is currently facing the contradiction between power supply shortage and demand growth. Almost three quarters of the electricity supply of China is derived from thermal power (mainly coal combustion). A proper projection of electricity consumption is helpful to deduce China's dependence on coal as a source of energy and thus will be helpful for the health of the environment. Therefore, it is necessary for the government to accurately predict the electricity demand. This paper employs both rolling mechanism and differential evolution algorithm to improve the prediction accuracy of the original grey model. Then, data from the China Federation of Electric Power Industry Development and Environmental Resources Department was adopted as database to test both the efficiency and accuracy of the improved prediction model. Experimental results show that the proposed model clearly outperforms the original grey model with regard to prediction accuracy. In addition, the future electricity consumption and power generation of China have been forecasted until 2025. The results will be useful to guide the electricity supply planning of the power department to promote the balance of power supply and demand. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1–34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2 (EIF2)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2-ATF4 signaling with two different inhibitors [AMG’44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alppositive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90- dependent PERK-EIF2-ATF4 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Kojibiose as a prebiotic and inhibitor of α-glucosidase exhibits potential for a wide range of applications in the food and medicine fields; however, large-scale separation and extraction of kojibiose from nature is difficult. Sucrose phosphorylase (SPase) can be used for the production of kojibiose, and currently, SPase is only heterologously expressed in E. coli, making it unsuitable for use in the food industry. However, Bacillus subtilis is generally considered to be a safe organism potentially useful for SPase expression. Results: Here, for the first time, we heterologously expressed Bifidobacterium adolescentis SPase in a food-grade B. subtilis strain. The results showed that SPase was efficiently secreted into the extracellular medium in the absence of a signal peptide. After culturing the recombinant strain in a 3-L bioreactor, crude SPase yield and activity reached 7.5 g/L and 5.3 U/mL, respectively, the highest levels reported to date. The optimal reaction conditions for kojibiose synthesis catalyzed by recombinant SPase were as follows: 0.5 M sucrose, 0.5 M glucose, 0.02 Uenzyme/mgall_substrates, pH 7.0, 50 °C, and 30 h. Furthermore, the substrate-conversion rate reached 40.01%, with kojibiose accounting for 104.45 g/L and selectivity for kojibiose production at 97%. Conclusions: Here, we successfully expressed SPase in B. subtilis in the absence of a signal peptide and demonstrated its secretion into the extracellular medium. Our results indicated high levels of recombinant enzyme expression, with a substrate-conversion rate of 40.01%. These results provide a basis for large-scale preparation of kojibiose by the recombinant SPase. [ABSTRACT FROM AUTHOR]

The ε-β fishlike phase diagram of the system [C16mim]Br/[Omim]Tf2N/water was constructed in the presence of different additives (alcohol and inorganic salt). From the diagram some additive-dependent characteristic physicochemical parameters were obtained. Results show that with the increase of the alkyl chain length of alcohols, the solubility of the alcohol in [Omim]Tf2N, and the optimum solubilization parameter (SP*) decrease, while the maximum alcohol width (△ε) for the phase inversion and the mass fraction of the alcohol in the balanced interfacial film (Ain) increase. For inorganic salts, an increase in [NaCl], or an increase of the radius of halides (X-) at constant [NaX], or the substitution of the divalent anion SO42- by the same molar concentration of monovalent anion Cl- makes both SP* and △ε increase, but Ain decrease. Overall, the alcohol effect on the phase behavior of the microemulsion is greater than the salt effect, and the composition effect of an inorganic salt is greater than the concentration effect. These effects could be rationalized based on their influence on the dissolution and aggregation behavior of the surfactant [C16mim]Br in the system. [ABSTRACT FROM AUTHOR]

Since a representative dataset of the climatological features of a location is important for calculations relating to many fields, such as solar energy system, agriculture, meteorology and architecture, there is a need to investigate the methodology for generating a typical meteorological year (TMY). In this paper, a hybrid method with mixed treatment of selected results from the Danish method, the Festa-Ratto method, and the modified typical meteorological year method is proposed to determine typical meteorological years for 35 locations in six different climatic zones of China (Tropical Zone, Subtropical Zone, Warm Temperate Zone, Mid Temperate Zone, Cold Temperate Zone and Tibetan Plateau Zone). Measured weather data (air dry-bulb temperature, air relative humidity, wind speed, pressure, sunshine duration and global solar radiation), which cover the period of 1994-2015, are obtained and applied in the process of forming TMY. The TMY data and typical solar radiation data are investigated and analyzed in this study. It is found that the results of the hybrid method have better performance in terms of the long-term average measured data during the year than the other investigated methods. Moreover, the Gaussian process regression (GPR) model is recommended to forecast the monthly mean solar radiation using the last 22 years (1994-2015) of measured data. [ABSTRACT FROM AUTHOR]

Serum samples collected from California women at different time periods: 1960s (n = 40), 1980s (n = 30), and 2009 (n = 35) were examined for the presence of 12 perfluorinated compounds (PFCs) using an online SPE-HPLC-MS/MS method. At each time period, perfluorooctane sulfonate (PFOS) was present at the highest concentration, followed by perfluorooctanoic acid (PFOA, except in the 1960s). We found the highest levels of PFOS (median = 42.1 ng/mL) and perfluorohexane sulfonate (PFHxS, median = 1.56 ng/mL) in the 1960s samples, possibly reflecting widespread use of precursor PFCs. PFOS showed a statistically significant drop from the 1960s to the 1980s (28.8 ng/mL ) and to 2009 (9.0 ng/mL ), the latter being in agreement with national data. For PFOA, there was an approximately 10-fold increase in median concentrations from the 1960s (0.27 ng/mL) to the 1980s (2.71 ng/mL), and a slight drop in the 2009 samples (2.08 ng/mL). For longer chain perfluorocarboxylic acids (PFCAs), there was a continuous build-up in serum from the 1960s to 2009. To our knowledge, this is the first study to investigate temporal changes of PFCs over the past 50 years. [ABSTRACT FROM AUTHOR]

A method to optimize the thermal deformation of an indirectly cryo-cooled silicon crystal monochromator exposed to intense X-rays at a low-emittance diffraction-limited synchrotron radiation source is presented. The thermalinduced slope error of the monochromator crystal has been studied as a function of heat transfer efficiency, crystal temperature distribution and beam footprint size. A partial cooling method is proposed, which flattens the crystal surface profile within the beam footprint by modifying the cooling contact area to optimize the crystal peak temperature. The optimal temperature varies with different photon energies, which is investigated, and a proper cooling strategy is obtained to fulfil the thermal distortion requirements over the entire photon energy range. At an absorbed power up to 300 W with a maximum power density of 44.8 W mm-2 normal incidence beam from an in-vacuum undulator, the crystal thermal distortion does not exceed 0.3 mrad at 8.33 keV. This method will provide references for the monochromator design on diffraction-limited synchrotron radiation or free-electron laser light sources. [ABSTRACT FROM AUTHOR]

Propanol stimulates erythromycin biosynthesis by increasing the supply of propionyl coenzyme A (propionyl-CoA), a starter unit of erythromycin production in Saccharopolyspora erythraea. Propionyl-CoA is assimilated via propionyl-CoA carboxylase to methylmalonyl-CoA, an extender unit of erythromycin. We found that the addition of n-propanol or propionate caused a 4- to 16-fold increase in the transcriptional levels of the SACE_3398-3400 locus encoding propionyl-CoA carboxylase, a key enzyme in propionate metabolism. The regulator PccD was proved to be directly involved in the transcription regulation of the SACE_3398-3400 locus by EMSA and DNase I footprint analysis. The transcriptional levels of SACE_3398-3400 were upregulated 15- to 37-fold in the pccD gene deletion strain (ΔpccD) and downregulated 3-fold in the pccD overexpression strain (WT/pIB-pccD), indicating that PccD was a negative transcriptional regulator of SACE_3398-3400. The ΔpccD strain has a higher growth rate than that of the wild-type strain (WT) on Evans medium with propionate as the sole carbon source, whereas the growth of the WT/pIB-pccD strain was repressed. As a possible metabolite of propionate metabolism, methylmalonic acid was identified as an effector molecule of PccD and repressed its regulatory activity. A higher level of erythromycin in the ΔpccD strain was observed compared with that in the wild-type strain. Our study reveals a regulatory mechanism in propionate metabolism and suggests new possibilities for designing metabolic engineering to increase erythromycin yield. [ABSTRACT FROM AUTHOR]

It will be demonstrated that the electron tunneling spectroscopy (ETS), obtained by taking the second derivative of the current-voltage (I–V) characteristic of a tunnel barrier, is an effective technique to probe traps in ultra-thin gate dielectrics where significant tunneling currents flow. By taking the electron tunneling spectra in both polarities, one can determine the locations and energy levels of traps that appear in the ETS spectra. The procedure for the above and the associated derivation will be presented. Examples are shown to demonstrate the use of ETS to track the evolution of traps in high-k gate dielectrics under electrical stress. [ABSTRACT FROM AUTHOR]

Reports on the novel binding and efficient cellular uptake of guanidine-based peptide nucleic acid (GPNA). Characterization of the binding properties of GPNA by circular dichroism; Evaluation of the uptake properties of GPNA with human colon and osteosarcoma cell lines using fluorescence microscope.

BACKGROUND: Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications. OBJECTIVES: We characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco. METHODS: We collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures. RESULTS: We detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between -0.1 and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (coefficient=0.9, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [OR=1.33 (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [OR=1.28 (95% CI: 0.90, 1.86)]. DISCUSSION: We identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. [ABSTRACT FROM AUTHOR]

After several decades of widespread use, some per- and polyfluoroalkyl substances (PFASs) were phased-out of use due to concerns raised by their persistent, bioaccumulative, and toxic properties. Our objective was to evaluate temporal trends in serum PFAS levels among 1257 middle-aged and older California women (ages 40-94) during a four year period, beginning approximately 5-10 years after these phase-outs began. An online SPE-HPLC-MS/MS was used to measure 10 long-chain PFASs in serum from blood collected cross-sectionally during 2011-2015 from a subset of participants in the California Teachers Study. Results from multivariable linear regression analyses indicated that serum concentrations of nearly all PFASs declined on average 10% to 20% per year. Serum levels of perfluorohexanesulfonic acid (PFHxS) did not significantly decline. With the exception of PFHxS, the downward trend in serum concentrations was evident for all PFASs across all ages, although declines were comparatively steeper among the oldest women. These findings suggest that the phase-out of some common PFASs has resulted in reduced human exposures to them. The lack of a decline for PFHxS suggests that these exposures may be ongoing and underscores the importance of continued biomonitoring and research efforts to elucidate current pathways of exposure. [ABSTRACT FROM AUTHOR]

Drought stress is one of the major environmental obstacles that limit the production and development of apples (Malus domestica Borkh.). The role of melatonin is well known in the protection of plants under environmental stresses. In this study, we investigated the effect of melatonin on apple rootstock M. hupehensis Rehd under drought stress. The results showed that drought inhibited the growth of M. hupehensis and dramatically reduced root surface area, root volume, the number of tips and forks, and root diameter. Drought-induced growth inhibition was significantly decreased by adding melatonin. Net photosynthetic rate (Pn), intercellular CO2 concentration (Ci), stomatal conductance (Gs), transpiration rate (Tr), were markedly reduced under drought stress. However, the application of melatonin could mitigate the damage to the photosynthetic apparatus and increase the quantum yield of PSII photochemistry. Additionally, generation of hydrogen peroxide (H2O2) and superoxide radicals (O2 •-) sharply increased in apple leaves after 4 days under drought stress, and the accumulation of electrolyte leakage (EL) represented oxidative stress, while by applying melatonin under drought stress, the generation of O2 •- and H2O2 were significantly reduced and protected the membrane from drought damages. These results suggest that the adverse effects of drought can be minimized by applying melatonin to apples. [ABSTRACT FROM AUTHOR]

A recent genome-wide association study identified two common variants that confer susceptibility to bladder cancer. We hypothesized that these variants are associated with risk of bladder cancer in Chinese populations. We genotyped rs9642880 G>T on 8q24 and rs710521 A>G on 3q28 in a two-stage case–control study of bladder cancer to evaluate the association and further examined the expression of MYC. We found that the rs9642880 G>T, but not the rs710521 A>G polymorphism, was associated with an increased risk of bladder cancer. Compared with the rs9642880 GG genotype, the GT/TT genotypes were associated with an odds ratio of 1.65 (95% confidence interval = 1.25–2.17), and this risk was more pronounced in young men and for low-risk tumors. Additional experiments revealed that the rs9642880 GT/TT genotypes were associated with enhanced levels of both MYC mRNA and protein in bladder tissues. Our findings suggested that the rs9642880 G>T polymorphism on 8q24 was independently associated with the risk of bladder cancer in Chinese populations. [ABSTRACT FROM AUTHOR]

Background/aim: Hypoxia-induced pulmonary arterial hypertension (PAH) is characterized by prostacyclin (PGI2) disorder, which manifests in the same manner as in monocrotaline (MCT)-induced PAH. Endogenous PGI2 inhibitor coupling factor 6 (CF6) is involved in MCT-induced PAH. This study aimed to explore the presence or absence of a correlation between hypoxia-induced PAH and CF6. Materials and methods: This study was conducted between January 2019 and June 2020. A total of 135 male Wistar rats (aged 8 weeks and weighing 200-250 g) were randomly divided into five groups: (A) control, (B) 1 week of hypoxia, (C) 2 weeks of hypoxia, (D) 3 weeks of hypoxia, and (E) 4 weeks of hypoxia. CF6 expression in both lung tissue and blood samples from the lung vasculature and tail vein was measured by western blotting, immunohistochemistry, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay. Results: Hemodynamic and morphological changes in hypoxia-induced rats indicated PAH development. The results showed the presence of a correlation between the mRNA and protein levels of CF6 in lung tissue, activity of mitochondrial ATP synthase, and hypoxia time, and there was a significant increment in the group exposed to hypoxia for 4 weeks compared to the control group. The decrement expression of ATPase inhibitory factor 1 (IF 1) mRNA was consistent with the outcomes of ATP synthase activity in lung tissue in the 4 weeks of hypoxia group compared with the control group. However, the levels of CF6 and ATP synthase activity did not differ between blood samples from the lung vasculature and tail vein. Conclusion: In hypoxia-induced PAH, CF6 showed downregulated expression in lung tissue, but not in pulmonary vasculature and circulation. Therefore, we speculated that CF6 and ATP synthase may play important roles in hypoxia-induced PAH. [ABSTRACT FROM AUTHOR]

The aim of this study was evaluation of effect of heat shock protein 70 on toll-like receptor 4 and toll-like receptor 2 in melanoma cell line, A-375. The melanoma cell lines were stimulated in time course with heat shock protein 70 protein and incubation was performed. After 48 h, the cells were collected and total messenger ribonucleic acid was extracted and the expression of toll-like receptor 2 and toll-like receptor 4 was determined by quantitative reverse transcription polymerase chain reaction. The results showed that the appearance of toll-like receptor 2, toll-like receptor 4 in melanoma cell line, A-375 decreased in exposure to heat shock protein 70. The results showed the expression of nuclear factor kappa B in melanoma cell line. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide evaluation results of melanoma cell death were compared at different times and statistical analysis showed a significant difference (p<0.001). The role of heat shock protein 70 has been identified as a tumor suppressor in melanoma cancer. Heat shock protein 70 is a new treatment for melanoma in the near future. Heat shock protein 70 can be considered as a potential target in gene therapy for patients with melanoma cancer and the advantages of gene therapy by heat shock protein 70 in this type of cancer over chemotherapy can reduce cytotoxic effects and its low invasiveness. [ABSTRACT FROM AUTHOR]

We examined a dual-path model to explain the opposite roles of career adaptability and organizational performance. We used a time-lagged survey of 53 supervisors and 327 employees in China to collect data. Results show that career-oriented proactive behavior mediated the negative effect of career adaptability on performance, and work unitoriented proactive behavior mediated the positive effect of career adaptability on performance. Moreover, the effects of career adaptability and career-oriented proactive behavior on performance were significant only for employees with high independent selfconstrual, and the effects of career adaptability and work unit-oriented proactive behavior on performance were significant only for employees with high interdependent self-construal. This study extends career construction theory in the organizational behavior field and has practical significance for the effective guiding of adaptable employees' contribution to organizational performance. [ABSTRACT FROM AUTHOR]

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic Escherichia coli (EPEC) by shutting down an infection-responsive signal of the host intestine cell. A key step in EPEC infection of intestinal cells involves Tir-induced actin reorganization. Nck mediates this event by binding with Tir through its SH2 domain (Nck-SH2) and with WIP through its second SH3 domain (Nck-SH3.2). Here we report the design of a synthetic peptide that reacts precisely with a unique cysteine of the Nck-SH3.2 domain, blocks the binding site of the Nck protein, and prevents EPEC infection of Caco-2 cells. Oral update of this nontoxic peptide before EPEC administration safeguards mice from EPEC infection and diarrhea. This study demonstrates domain-specific blockage of an SH3 domain of a multidomain adaptor protein inside cells and the inhibition of Tir-induced rearrangement of the host actin cytoskeleton as a previously unknown antibacterial mechanism. [ABSTRACT FROM AUTHOR]

Objectives: Postresuscitation care bundle treatment after return of spontaneous circulation in patients experiencing in-hospital cardiac arrest can improve patients' survival and quality of life. The aim of the study was to evaluate the efficacy and safety of combined therapy of Shenfu injection and postresuscitation care bundle in these patients.Design: Prospective, randomized, controlled clinical study.Setting: Fifty hospitals in China.Patients: Adult patients had experienced in-hospital cardiac arrest between 2012 and 2015.Interventions: Based on the standardized postresuscitation care bundle treatment, patients were randomized to a Shenfu injection group (Shenfu injection + postresuscitation care bundle) or control group (postresuscitation care bundle) for 14 days or until hospital discharge. In the Shenfu injection group, 100 mL Shenfu injection was additionally administered via continuous IV infusion, bid.Measurements and Main Results: The primary outcome was 28-day survival after randomization. The secondary outcomes included 90-day survival as well as the duration of mechanical ventilation and the hospital stay and the total cost of hospitalization. Of 1,022 patients enrolled, a total of 978 patients were allocated to the two groups: the control (n = 486) and Shenfu injection (n = 492) groups. The Shenfu injection group had a significantly greater 28-day survival rate (42.7%) than the control group (30.1%). Also, the Shenfu injection group had a significantly higher survival rate at 90 days (39.6%) than the control group (25.9%). Compared with patients in the control group, patients in the Shenfu injection group had lower risks of 28-day mortality (hazard ratio, 0.61; 95% CI, 0.43-0.89; p = 0.009) and 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79; p = 0.002). In the Shenfu injection group, the duration of mechanical ventilation (8.6 ± 3.2 vs 12.7 ± 7.9 d; p < 0.001) and the hospital stay (8.7 ± 5.9 vs 13.2 ± 8.1 d; p < 0.001) were significantly less than in the control group. Irreversible brain damage was the main cause of death in both groups. No serious drug-related adverse event was recorded.Conclusions: This study demonstrates that Shenfu injection in combination with conventional postresuscitation care bundle treatment is effective at improving clinical outcomes in patients with return of spontaneous circulation after in-hospital cardiac arrest. [ABSTRACT FROM AUTHOR]

Background: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. Sildenafil has been shown to attenuate postresuscitation myocardial dysfunction in piget models of ventricular fibrillation. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by attenuating apoptosis and regulating miRNA expressions, furthermore, ameliorating the severity of post-microcirculatory dysfunction. Methods: Twenty-four male pigs (weighing 30 ± 2 kg) were randomly divided into groups, sildenafil pretreatment (n = 8), saline (n = 8) and sham operation (sham, n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil, administered once intraperitoneally 30 min prior to ventricular fibrillation (VF). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and hearts were removed for analysis by electron microscopy, western blotting, quantitative real-time polymerase chain reaction (PCR), and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Intestinal microcirculatory blood flow was visualized by a sidestream dark-field imaging device at baseline and 0.5, 1, 2, 4, and 6 h after ROSC. Results: Compared with the saline group, the sildenafil group had a higher 24-hour survival (7/8 versus 3/8 survivors, p < 0.05) and a better outcome in hemodynamic parameters. The protective effect of sildenafil also correlated with reduced cardiomyocyte apoptosis, as evidenced by reduced TUNEL-positive cells, increased anti-apoptotic Bcl-2/Bax ratio and inhibited caspase-3 activity in myocardium. Additionally, sildenafil treatment inhibited the increases in the microRNA-1 levels and alleviated the decreases in the microRNA-133a levels which negatively regulates pro-apoptotic genes. At 6 h after ROSC, post-resuscitation perfused vessel density and microcirculatory flow index were significantly lower in the saline group than in the sildenafil group. Conclusions: The major findings of this study are as follows: (1) sildenafil improved post-resuscitation perfusion of the heart, and thus reduced cardiac myocyte apoptosis and improved cardiac function; (2) sildenafil treatment inhibited the increases in the microRNA-1 levels, but alleviated the decreases in the microRNA-133a levels. [ABSTRACT FROM AUTHOR]

Objective: To assess California firefighters' blood concentrations of selected chemicals and compare with a representative US population. Methods: We report laboratory methods and analytic results for cadmium, lead, mercury, and manganese in whole blood and 12 serum perfluorinated chemicals in a sample of 101 Southern California firefighters. Results: Firefighters' blood metal concentrations were all similar to or lower than the National Health and Nutrition Examination Survey (NHANES) values, except for six participants whose mercury concentrations (range: 9.79 to 13.42 yug/L) were close to or higher than the NHANES reporting threshold of 10 /ug/L. Perfluorodecanoic acid concentrations were elevated compared with NHANES and other firefighter studies. Conclusions: Perfiuorodecanoic acid concentrations were three times higher in this firefighter group than in NHANES adult males. Firefighters may have unidentified sources of occupational exposure to perfluorinated chemicals. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment [ABSTRACT FROM AUTHOR]

Cyclin D1 (CCND1) is a key protein in regulation of cell cycle at the G1-to-S transition phase and is essential for regulation of cell proliferation, differentiation, and transcriptional control. We hypothesized that the CCND1 G870A polymorphism is associated with risk of bladder cancer. The CCND1 G870A polymorphism was genotyped in a hospital-based case-control study of 402 bladder cancer cases and 402 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Unconditional univariate and multivariate logistic regression analyses were used to evaluate the associations between the CCND1 G870A polymorphism and bladder cancer risk. A significantly increased risk of bladder cancer was associated with the combined variant CCND1 870GA/AA genotypes (adjusted odds ratio, 1.54; 95% confidence interval, 1.08-2.20) compared with the GG genotype, particularly among subgroups of age ≥65 years (1.74; 1.06-2.88), men (1.67; 1.15-2.44), and smokers (1.82; 1.12-2.93). Further, the G870A polymorphism was significantly associated with risk of developing superficial bladder cancer (grade 1). In addition, a meta-analysis of the G870A polymorphism and bladder cancer risk showed that the variant 870GA/AA genotypes were associated with an increased risk of bladder cancer in Asians, but not in Caucasians, which was consistent with the results of our study. The CCND1 G870A polymorphism may be a marker for the development of bladder cancer in Chinese populations. Larger studies are required to validate these findings in diverse populations. [ABSTRACT FROM AUTHOR]

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case–control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16–3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05–1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4–6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03–2.53) compared with those with 0–3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03–2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer. [ABSTRACT FROM AUTHOR]