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Digital transformation enables small and medium enterprises (SMEs) to reduce or overcome their reliance on resources and energy, thereby minimizing their environmental impact and providing them with sustainable green competitive advantages. However, the reasons for this phenomenon are not yet clear. To further investigate this issue, we selected 391 Chinese SMEs to examine the relationships among green transformation, green innovation, government regulation, and green competitive advantages. Green innovation includes green product innovation and green process innovation, while government regulation includes incentive regulation, constraint regulation, and guidance regulation. The empirical results show that digital transformation can enhance SMEs' green competitive advantages. Additionally, the hypothesized mediating effect of green product innovation and green process innovation between digital transformation and green competitive advantages is supported, while the moderating effect of incentive regulation, constraint regulation, and guidance regulation on the relationship between digital transformation and green product innovation and green process innovation is also confirmed. The findings of this study may contribute to more effective management of digital transformation and green innovation in SMEs, thereby promoting their development.

The land use changes driven by human activities press a incredible menace to zonal ecological security. As the most active urban cluster, the uncontrolled expansion of cities in the bay area exerts enormous pressure on the ecosystem. Therefore, from the perspective of ecological conservation, exploring future land use optimization patterns and spatial structure is extremely essential for the long-term thriving of the bay area. On this basis, this research integrated the System Dynamics model (SD) as the quantity forecast model and the PLUS model as the spatial emulation model and established the Land Use/Cover Change (LUCC) Simulation Framework by setting the constraints of Ecological Security Multi-Scenario Patterns (ESMP). By setting four scenarios in future, that is, Business As Usual (BAU), Priority of Ecological Protection (PEP), Balanced Development Scenario (BD), and Priority of Urban development (PUD), this research predicts LUCC in the Zhejiang Greater Bay Area (ZGBA) in 2035 and explored land use optimization patterns. The results indicate that by 2035, under the scenarios of BAU, BD, and PUD, the construction land will observably grow by 38.86%, 19.63%, and 83.90%, respectively, distributed mainly around the Hangzhou Bay Area, Taizhou Bay Area, and Wenzhou Bay Area, primarily achieved by sacrificing ecologically sensitive lands such as forests to achieve regional high economic growth. Under PEP, the growth of construction land retards, and forest experiences net growth (11.27%), with better landscape connectivity and more cohesive patches compared to other scenarios. Combining regional planning and analysis at the city scale, Hangzhou Bay area (Hangzhou, Huzhou, Jiaxing, Shaoxing, Ningbo) can adopt the BD development scenario, while Zhoushan, Taizhou, Wenzhou and Fuyang County of Hangzhou can adopt the PEP development scenario. This research furnishes a novel mechanism for optimizing land use pattern in ecological security perspective and offers scientific guidance for land resource management and spatial planning in ZGBA.

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits, but severe winter defoliation affects the following year's yield, and the response mechanism of lemon defoliation is currently unknown. Two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemons. The petiole abscission zone was collected at three different defoliation stages, namely, the predefoliation stage (k15), the middefoliation stage (k30), and the postdefoliation stage (k45). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 1141, 2695, and 1433 differentially expressed genes (DEGs) were obtained in k15, k30, and k45, respectively, and the number of DEGs in k30 was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to hydrolase activity, chitinase activity, oxidoreductase activity, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in k30, which involved plant hormone signal transduction, phenylpropanoid biosynthesis, and biosynthesis of amino acids. The expression trends of some DEGs suggested their roles in regulating defoliation in Lemon. Seven genes were obtained by WGCNA, including sorbitol dehydrogenase (CL9G068822012_alt, CL9G068820012_alt, CL9G068818012_alt), abscisic acid 8'-hydroxylase (CL8G064053012_alt, CL8G064054012_alt), and asparagine synthetase (CL8G065162012_alt, CL8G065151012_alt), suggesting that these genes may be involved in the regulation of lemon leaf abscission.

The primary energy consumption structure of BRICS countries is dominated by fossil energy, particularly coal. Coal consumption in BRICS countries is a major driver underlying increased carbon emissions. Therefore, this study developed a spatiotemporal decoupling mode and incorporated factors related to coal consumption-induced carbon emissions into a spatiotemporal decoupling analysis method to provide differentiated and targeted policies for energy restructuring and emission reduction targets in BRICS countries. Moreover, a temporal-spatial decomposition logarithmic mean Divisia index model was developed using the spatiotemporal decoupling index method. The model is based on CO2 emissions generated by coal consumption in BRICS countries, with a primary focus on data from Brazil, Russia, South Africa, India, and China. The findings reveal distinct spatiotemporal distributions and driving effects of coal consumption and carbon dioxide emissions across various countries. Factors such as CO2 emission intensity, coal consumption intensity, economic output per capita, and population structure exerted either positive or negative effects on the distributional effect of the carbon emission-economic output per capita association in BRICS countries. Additionally, country-level heterogeneity in the influence of the distributional effects of CO2 emissions was observed within each BRICS country. Thus, different policies are needed to achieve carbon emission reduction targets in different countries.

Background and aimPrimarily, this study compares the efficacy of probiotic and acceptance and commitment therapy (ACT) in alleviating the severity of alcohol craving and alcohol use disorder (AUD) among patients who had undergo two weeks of in-patient detoxification. Secondarily, this study compares the efficacy of probiotic and ACT in mitigating the severity of comorbid depression and anxiety symptoms; decreasing serum level of pro-inflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); changing the event-related potential in electroencephalogram (EEG) and restoring microbiota flora in the gut of AUD patients.Methods and analysisInitially, during Phase I of the study, the serum level of IL-1β, IL-6 and TNF-α; ERP changes in the EEG and fecal microbiota content will be compared between 120 AUD patients and 120 healthy controls. Subsequently in Phase II of the study, 120 AUD patients will be randomized by stratified permuted block randomization into the probiotic, ACT and placebo groups in a 1:1:1 ratio. Participants in the probiotic and placebo groups will be administered one sachet per day of Lactobacillus spp. probiotic and placebo, respectively for 12 weeks. While those in the ACT group will receive one session per week of ACT for 8 weeks. Outcome measures will be administered at four timepoints, such as t0 = baseline assessment prior to intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention and t3 = 24 weeks after intervention. Primary outcomes are the degrees of alcohol craving, alcohol withdrawal during abstinence and AUD. Secondary outcomes to be assessed are the severity of co-morbid depression and anxiety symptoms; the serum levels of IL-1β, IL-6 and TNF-α; changes in ERP and fecal microbiota content.Trial registration numberNCT05830708 (ClinicalTrials.gov). Registered on April 25, 2023.

[This corrects the article DOI: 10.1371/journal.pone.0257901.].

The balanced development of ecological quality and residents' well-being is an important factor in achieving sustainable economic development in rural counties. In order to promote the improvement of the coupling coordination degree between ecology and well-being in rural counties, this study explores the impact mechanism of industrial structural transformation and upgrading on the coupling of ecology and well-being in the Sichuan-Chongqing. A dual-fixed-space Durbin model is constructed to analyze the influence mechanism and spatial interaction effects of industrial transformation and upgrading on the coordination of ecology and well-being. The research indicates: (1) From 2010 to 2020, the overall coordination degree of ecology and well-being in the Sichuan-Chongqing rural counties has steadily increased, with higher coordination in the eastern region and lower coordination in the western region. The growth rate of coordination degree is faster in the east and slower in the west, with significant and increasing differences between the east and west. 2) The coupling coordination degree of ecology and well-being in the Sichuan-Chongqing rural counties has a strong positive spatial spillover effect. (3) The more reasonable the industrial structure, the higher the level of coordinated development in the local and surrounding rural counties. The higher the index of industrial advancement, the better the level of coordinated development locally, but the lower the level of coordinated development in the surrounding areas.

The diffusion phenomena taking place in complex networks are usually modelled as diffusion process, such as the diffusion of diseases, rumors and viruses. Identification of diffusion source is crucial for developing strategies to control these harmful diffusion processes. At present, accurately identifying the diffusion source is still an opening challenge. In this paper, we define a kind of diffusion characteristics that is composed of the diffusion direction and time information of observers, and propose a neural networks based diffusion characteristics classification framework (NN-DCCF) to identify the source. The NN-DCCF contains three stages. First, the diffusion characteristics are utilized to construct network snapshot feature. Then, a graph LSTM auto-encoder is proposed to convert the network snapshot feature into low-dimension representation vectors. Further, a source classification neural network is proposed to identify the diffusion source by classifying the representation vectors. With NN-DCCF, the identification of diffusion source is converted into a classification problem. Experiments are performed on a series of synthetic and real networks. The results show that the NN-DCCF is feasible and effective in accurately identifying the diffusion source.

BackgroundResearch into mood and emotion has often depended on slow and subjective self-report, highlighting a need for rapid, accurate, and objective assessment tools.MethodsTo address this gap, we developed a method using digital image speckle correlation (DISC), which tracks subtle changes in facial expressions invisible to the naked eye, to assess emotions in real-time. We presented ten participants with visual stimuli triggering neutral, happy, and sad emotions and quantified their associated facial responses via detailed DISC analysis.ResultsWe identified key alterations in facial expression (facial maps) that reliably signal changes in mood state across all individuals based on these data. Furthermore, principal component analysis of these facial maps identified regions associated with happy and sad emotions. Compared with commercial deep learning solutions that use individual images to detect facial expressions and classify emotions, such as Amazon Rekognition, our DISC-based classifiers utilize frame-to-frame changes. Our data show that DISC-based classifiers deliver substantially better predictions, and they are inherently free of racial or gender bias.LimitationsOur sample size was limited, and participants were aware their faces were recorded on video. Despite this, our results remained consistent across individuals.ConclusionsWe demonstrate that DISC-based facial analysis can be used to reliably identify an individual's emotion and may provide a robust and economic modality for real-time, noninvasive clinical monitoring in the future.

To estimate the incidence of foodborne gastroenteritis caused by nontyphoidal Salmonella enterica, Shigella, and Vibrio parahaemolyticus in China, population surveys and sentinel hospital surveillance were implemented in six provinces from July 2010 to July 2011, and a multiplier calculation model for the burden of disease was constructed. The multiplier for salmonellosis and V. parahaemolyticus gastroenteritis was estimated at 4,137 [95% confidence interval (CI) 2,320-5,663], and for shigellosis at 4,356 (95% CI 2,443-5,963). Annual incidence per 100,000 population was estimated as 245 (95% CI 138-336), 67 (95% CI 38-92), and 806 (95% CI 452-1,103) for foodborne salmonellosis, shigellosis, and V. parahaemolyticus gastroenteritis, respectively, indicating that foodborne infection caused by these three pathogens constitutes an important burden to the Chinese healthcare system. Continuous implementation of active surveillance of foodborne diseases, combined with multiplier models to estimate disease burden, makes it possible for us to better understand food safety status in China.

Drug-drug interaction (DDI) prediction has received considerable attention from industry and academia. Most existing methods predict DDIs from drug attributes or relationships with neighbors, which does not guarantee that informative drug embeddings for prediction will be obtained. To address this limitation, we propose a multitype drug interaction prediction method based on the deep fusion of drug features and topological relationships, abbreviated DM-DDI. The proposed method adopts a deep fusion strategy to combine drug features and topologies to learn representative drug embeddings for DDI prediction. Specifically, a deep neural network model is first used on the drug feature matrix to extract feature information, while a graph convolutional network model is employed to capture structural information from the adjacency matrix. Then, we adopt delivery operations that allow the two models to exchange information between layers, as well as an attention mechanism for a weighted fusion of the two learned embeddings before the output layer. Finally, the unified drug embeddings for the downstream task are obtained. We conducted extensive experiments on real-world datasets, the experimental results demonstrated that DM-DDI achieved more accurate prediction results than state-of-the-art baselines. Furthermore, in two tasks that are more similar to real-world scenarios, DM-DDI outperformed other prediction methods for unknown drugs.

BackgroundThis study aimed to establish a traumatic hemorrhagic shock (THS) model in swine and examine pathophysiological characteristics in a dry-heat environment.MethodsForty domestic Landrace piglets were randomly assigned to four study groups: normal temperature non-shock (NS), normal temperature THS (NTHS), desert dry-heat non-shock (DS), and desert dry-hot THS (DTHS) groups. The groups were exposed to either normal temperature (25°C) or dry heat (40.5°C) for 3 h. To induce THS, anesthetized piglets in the NTHS and DTHS groups were subjected to liver trauma and hypovolemic shock until death, and piglets in the NS and DS groups were euthanized at 11 h and 4 h, respectively. Body temperature, blood gas, cytokine production, and organ function were assessed before and after environmental exposure at 0 h and at every 30 min after shock to death. Hemodynamics was measured post exposure and post-shock at 0 h and at every 30 min after shock to death.ResultsSurvival, body temperature, oxygen delivery, oxygen consumption, and cardiac output were significantly different for traumatic hemorrhagic shock in the dry-heat groups compared to those in the normal temperature groups. Lactic acid and IL-6 had a marked increase at 0.5 h, followed by a progressive and rapid increase in the DTHS group.ConclusionsOur findings suggest that the combined action of a dry-heat environment and THS leads to higher oxygen metabolism, poorer hemodynamic stability, and earlier and more severe inflammatory response with higher mortality.

BackgroundIn recent years, autologous fat grafting (AFG), also known as fat transfer or lipofilling, has been widely performed for periorbital rejuvenation and defect correction, although the evidence regarding its efficacy and safety is still lacking. Besides, with respect to the periorbital region, it is invariably the earliest appearance area of the facial aging phenomenon. Therefore, a systematic review and meta-analysis is needed to evaluate the efficacy and safety of this technique.MethodsA literature search was performed in PubMed, Embase, and the Cochrane library databases on November 20, 2020, adhering to the PRISMA guidelines, to identify all relevant articles. Then, a data extraction and standardization process was performed to assess all outcome data. Ultimately, the data were assessed using a random effects regression model with comprehensive meta-analysis software.ResultsThirty-nine studies consisting of 3 cohorts and 36 case series with a total of 4046 cases were included. Meta-analysis revealed a relatively high satisfaction rate of 90.9% (95% CI, 86.4%-94.0%). Frequent complications in 4046 patients receiving AFG were edema, chemosis, and contour irregularity, with an overall complication rate of 7.9% (95% CI, 4.8%-12.8%).ConclusionThis systematic review and meta-analysis showed that AFG for rejuvenation of eyelids and periorbital area provided a high satisfaction rate and did not result in severe complications. Therefore, AFG might be performed safely for periorbital rejuvenation and reconstruction.

Adolescent girls and young women (AGYW) aged 15 to 24 years face disproportionately high risks of acquiring HIV and other sexually transmitted infections (STIs). A sexual health risk stratification tool can support the development and implementation of tailored HIV and STI prevention services for sub-groups of at-risk AGYW. Data were collected among sexually active AGYW aged 15 to 24 years in Tanzania between April 2015 and March 2017. Exploratory and confirmatory factor analyses were conducted to construct and assess the latent structure of a ten-item scale for rapid assessment of sexual health risks. Items with high factor loadings and minimal cross loadings were retained in the final scale. Scale performance was appraised against condomless sex (defined as unprotected vaginal or anal intercourse) reported by AGYW for construct validity. A three-factor structure of vulnerability to HIV among AGYW was supported with subscales for socioeconomic vulnerability; lack of adult support; and sexual behavioral risks. The chi-square goodness-of-fit test, root mean square error of approximation, comparative fit index, and Tucker-Lewis index indicated a strong goodness-of-fit of the three-factor scale. Cronbach alphas (0.55 for socioeconomic vulnerability, 0.55 for lack of support, and 0.48 for sexual risk) indicated sub-optimal internal consistency for all sub-scales. The factor-item and factor-factor correlations identified in these analyses were consistent with the conceptual framework of vulnerability of HIV infection in AGYW, suggesting good construct validity. The scale also demonstrated a statistically significant association with condomless sex and could be potentially used for sexual health risk stratification (OR = 1.17, 95% CI: 1.12, 1.23). The sexual health and HIV risk stratification scale demonstrated potential in identifying sexually active AGYW at high risk for HIV and other STIs. Ultimately, all AGYW in Tanzania are not at equal risk for HIV and this scale may support directing resources towards those at highest risk of HIV.

Phoneme pronunciations are usually considered as basic skills for learning a foreign language. Practicing the pronunciations in a computer-assisted way is helpful in a self-directed or long-distance learning environment. Recent researches indicate that machine learning is a promising method to build high-performance computer-assisted pronunciation training modalities. Many data-driven classifying models, such as support vector machines, back-propagation networks, deep neural networks and convolutional neural networks, are increasingly widely used for it. Yet, the acoustic waveforms of phoneme are essentially modulated from the base vibrations of vocal cords, and this fact somehow makes the predictors collinear, distorting the classifying models. A commonly-used solution to address this issue is to suppressing the collinearity of predictors via partial least square regressing algorithm. It allows to obtain high-quality predictor weighting results via predictor relationship analysis. However, as a linear regressor, the classifiers of this type possess very simple topology structures, constraining the universality of the regressors. For this issue, this paper presents an heterogeneous phoneme recognition framework which can further benefit the phoneme pronunciation diagnostic tasks by combining the partial least square with support vector machines. A French phoneme data set containing 4830 samples is established for the evaluation experiments. The experiments of this paper demonstrates that the new method improves the accuracy performance of the phoneme classifiers by 0.21 − 8.47% comparing to state-of-the-arts with different data training data density.

BackgroundThe population in Jiamusi has been reported to have the highest prevalence of colorectal cancer (CRC) in China. The genetic causal-effect for this occurrence among the residents remains unclear. Given the long cold seasons with people wearing more clothes and reduced UV exposure, we aimed to study the association between the vitamin D metabolism-related gene CYP24A1 polymorphism and CRC susceptibility.MethodA case-control study was conducted that included 168 patients with CRC and 710 age-matched healthy individuals as the control group. Plausible susceptible variations were sought and clinical phenotypic-genotype association analysis was performed.ResultsOverall, two CYP24A1 polymorphisms, rs6013905 AX (P = 0.02, OR = 1.89, 95%CI: 1.09-3.29) and rs2762939 GX (P = 0.02, OR = 1.52, 95%CI: 1.08-2.13) were significantly associated with CRC in the Jiamusi population. In the female group, three CYP24A1 polymorphisms, rs6013905 AX (P = 0.04, OR = 2.59, 95%CI: 1.03-6.49), rs2762939 GX (P = 0.01, OR = 2.35, 95%CI: 1.25-4.42), and rs6068816 GG (P = 0.05, OR = 1.89, 95%CI: 0.99-3.59) carriers were significantly associated with CRC. In clinical phenotypic-genotype analysis, rs6013905 GG (P = 0.05, OR = 4.00, 95%CI: 0.92-17.48) and rs2762939 GX (P = 0.03, OR = 4.87, 95%CI: 1.00-23.69) carriers were significantly associated with poorly differentiated CRC, while CYP24A1 rs6068816 AX was significantly associated with the tumor type (P = 0.02, OR = 2.08, 95%CI: 1.10-3.96) and location (P = 0.04, OR = 2.24, 95%CI: 1.05-4.77).ConclusionCYP24A1 gene polymorphism may be a genetic risk factor attributable to the highest prevalence of CRC in Jiamusi people. Individuals with CYP24A1 gene polymorphism may have an increased barrier for vitamin D absorption, thus contributing to the risk of CRC development.

Foam accumulation in swine manure deep-pits has been linked to explosions and flash fires that pose devastating threats to humans and livestock. It is clear that methane accumulation within these pits is the fuel for the fire; it is not understood what microbial drivers cause the accumulation and stabilization of methane. Here, we conducted a 13-month field study to survey the physical, chemical, and biological changes of pit-manure across 46 farms in Iowa. Our results showed that an increased methane production rate was associated with less digestible feed ingredients, suggesting that diet influences the storage pit's microbiome. Targeted sequencing of the bacterial 16S rRNA and archaeal mcrA genes was used to identify microbial communities' role and influence. We found that microbial communities in foaming and non-foaming manure were significantly different, and that the bacterial communities of foaming manure were more stable than those of non-foaming manure. Foaming manure methanogen communities were enriched with uncharacterized methanogens whose presence strongly correlated with high methane production rates. We also observed strong correlations between feed ration, manure characteristics, and the relative abundance of specific taxa, suggesting that manure foaming is linked to microbial community assemblage driven by efficient free long-chain fatty acid degradation by hydrogenotrophic methanogenesis.

Dalbergia odorifera T. Chen seedlings do not grow well in the typical red soils of tropical regions. Eighteen culture substances filled with different substrate combinations and proportions of red soil, coconut coir powder, deciduous leaf powder, and sand were used as to determine their effects on the growth, root system development, dry matter accumulation and allocation, leaf relative electrolyte leakage, chlorophyll content, root superoxide dismutase activity, root malondialdehyde content, and total soluble sugar content of D. odorifera. Results demonstrated that different substrate combinations and proportions had different effects on the performance of D. odorifera. All mixed substrates were better than any single substrate. The suitable substrate combinations and proportions of sand, coconut coir powder, and deciduous leaf powder mixed with red soil improved the growth, root architecture, and physiological characteristics of D. odorifera seedling. For example, groups C1-2 (coconut coir/red soil = 2/2, v/v, the same below) and C3-2 (red soil/sand = 2/2) exerted the best effects on plant growth and biomass accumulation. Groups C1-2, C2-2 (deciduous leaf powder/red soil = 2/2), and C3-2 remarkably enhanced root system development. Group C6 (coconut coir/red soil/sand = 1/1/1) substantially promoted root nodule development. Group C3-1 (red soil/sand = 3/1) exhibited the best effects on physiological characteristics. On the basis of the comprehensive evaluation of Euclid's multidimensional space mathematical model, we found that the suitable substrate combinations followed the order of C1-2 > C3-1 > C2-2. This research provides scientific guidance for the proper seedling culture of D. odorifera and the rational utilization of solid wastes such as coconut coir and deciduous leaves of Ficus elastica.

Strong early vigour plays a crucial role in wheat yield improvement by enhancing resource utilization efficiency. Synthetic hexaploid wheat (SHW) combines the elite genes of tetraploid wheat with Aegilops tauschii and has been widely used in wheat genetic improvement for its abundant genetic variation. The two SHWs Syn79 and Syn80 were derived from the crossing of the same tetraploid wheat DOY1 with two different Ae. tauschii accessions, AT333 and AT428, respectively. The Syn80 possessed better early vigour traits than Syn79, theretically caused by their D genome from Ae. tauschii. To dissect their genetic basis in a hexaploid background, 203 recombinant inbred lines (RILs) derived from the cross of Syn79 x Syn80 were developed to detect quantitative trait loci (QTL) for four early biomass related traits: plant height (PH), tiller number (TN), shoot fresh weight (SFW) and shoot dry weight (SDW) per plant, under five different environmental conditions. Determined from the data of SNP markers, two genome regions on 1DS and 7D were stably associated with the four early biomass related traits showing pleiotropic effects. Four stable QTLs QPh.saas-1DS, QTn.saas-1DS, QSfw.saas-1DS and QSdw.saas-1DS explaining 7.92, 15.34, 9.64 and 10.15% of the phenotypic variation, respectively, were clustered in the region of 1DS from AX-94812958 to AX-110910133. Meanwhile, QPh.saas-7D, QTn.saas-7D, QSfw.saas-7D and QSdw.saas-7D were flanked by AX-109917900 and AX-110605376 on 7D, explaining 16.12, 24.35, 15.25 and 13.37% of the phenotypic variation on average, respectively. Moreover, these genomic QTLs on 1DS and 7D enhancing biomass in the parent Syn80 were from Ae. tauschii AT428. These findings suggest that these two QTLs from Ae. tauschii can be expressed stably in a hexaploid background at the jointing stage and be used for wheat improvement.

Manure from animals that have been treated with antibiotics is often used to fertilize agricultural soils and its application has previously been shown to enrich for genes associated with antibiotic resistance in agroecosystems. To investigate the magnitude of this effect, we designed a column experiment simulating manure-treated agricultural soil that utilizes artificial subsurface drainage to determine the duration and extent which this type of manure fertilization impacts the set of genes associated with antibiotic resistance in drainage water. We classified ARGs in manure-treated drainage effluent water by its source of origin. Overall, we found that 61% and 7% of the total abundance of ARGs found in drainage water samples could be attributed to manure enrichment and manure addition, respectively. Among these ARGs, we identified 75 genes unique to manure that persisted in both soil and drainage water throughout a drainage season typical of the Upper Midwestern United States. While most of these genes gradually decreased in abundance over time, the IS6100-associated tet(33) gene accrued. These results demonstrate the influence of manure applications on the composition of the resistome observed in agricultural drainage water and highlight the importance of anthropogenic ARGs in the environment.

Naphthalene has been widely used to test the functional roles of soil fauna, but its nontarget effects remain uncertain in various soils. To determine whether there is a potential nontarget effect on soil biochemical properties in subalpine forest soil, soils in a subalpine forest on the western Qinghai-Tibet Plateau were treated by naphthalene in microcosms. The responses of soil microbial activity and nutrients to naphthalene were studied following 52 days of incubation. The results showed that the naphthalene application obviously decreased the microbial respiration rate in the first 10 days of the incubation and then increased the rate in the following days of the incubation. Moreover, the naphthalene application did not significantly affect the microbial activities overall, measured as soil microbial phospholipid fatty acid (PLFA) abundances and biomasses, or most enzyme activities (invertase, nitrate reductase and nitrite reductase) during the whole incubation period. However, naphthalene suppressed increases in the DON, NH4+-N and NO3--N contents and urease activity and led to the net mineralization of inorganic N (NH4+-N + NO3--N), in contrast to the net immobilization result in the controls. These results suggest that naphthalene can exert direct nontarget effects on soil microbial respiration and N mineralization processes in subalpine soils. Caution should be taken when using naphthalene to repel soil animals in field experiments.

Tear film breakup time (TFBUT) is an essential parameter used to diagnose dry eye disease (DED). However, a robust method for examining TFBUT in murine models has yet to be established. We invented an innovative device, namely, the "Smart Eye Camera", which addresses several problems associated with existing methods and is capable of evaluating TFBUT in a murine DED model. We compared images taken by existing devices and the Smart Eye Camera in a graft-versus-host disease-related DED murine model. We observed that the quality of the images obtained by the Smart Eye Camera were sufficient for practical use. Moreover, this new technique could be used to obtain measurements for several consecutive ocular phenotypes in a variety of environments. Here, we demonstrate the effectiveness of our new invention in the examination of ocular phenotypes, including TFBUT in a murine model. We highlight the potential for future translational studies adopting the Smart Eye Camera in clinical settings.

ObjectiveThis study was aimed to examine the effect of feeding patterns on growth and nutritional status of children aged 0~24 months.MethodsWe conducted a cohort study with an initial sample of 927 children. Considering the follow-up losses, 903, 897, 895, 897, 883, 827 and 750 children were followed up at 1, 3, 6, 8, 12, 18 and 24 months, respectively. Children were grouped according to exclusive breastfeeding (EBF) duration in the first 6 months: (1) never EBF; (2) EBF ≤ 3 months: EBF ≤ 3 months and stopped BF after 3 months or EBF ≤ 3 months and BF = 6 months or EBF ≤ 3 months and BF after 3 months, had formula and/or solids; (3) EBF for 3 ~ 6 months: BF < 3 months and EBF for 3 ~ 6 months or EBF for 3 ~ 6 months and BF < 3 months, had formula and/or solids; (4) EBF = 6 months. We used Z-scores to evaluate the growth and nutritional status of children, used the generalized estimation equation to compare the difference between feeding patterns.ResultsThe generalized estimation equation results showed that Weight-for-age Z-score (WAZ), Length-for-age Z-score (LAZ), and Weight-for-length Z-score (WLZ) in different feeding patterns had statistical significance. The WAZ in EBF for 6 months group was higher in the first 8 months, in never EBF group was higher after 12 months old; the LAZ in EBF for 6 month group was lower than other groups; the WLZ in EBF for 6 months group was higher than EBF for 3 ~ 6 months group. The EBF ≤ 3 months group had higher underweight, stunting, and wasting rates. The EBF for 6 months had a higher stunting rate; the never EBF and EBF for 6 months groups had higher overweight and obesity rates.ConclusionsIn conclusion, different feeding patterns affect growth and nutritional status in children, so proper guidelines should be implemented to improve nutritional status and promote the growth of children.

New radiochemistry techniques can yield novel PET tracers for COX-2 and address the shortcomings in in vivo stability and specificity, which have held back clinical translation of tracers to image COX-2 expression. Current techniques limit radiosynthesis to analogs of the COX-2 inhibitors with fluorine-18 added via a carbon chain, or on an aromatic position which renders the radiolabeled analog less specific towards COX-2, resulting in tracers with low in vivo stability or specificity. To solve this problem, we have developed a new high affinity, 18F-labelled COX-2 inhibitor that is radiolabeled directly on a heteroaromatic ring. This molecule exhibits favorable biodistribution and increased metabolic stability. Synthesis of this molecule cannot be achieved by traditional means; consequently, we have developed an automated electrochemical radiosynthesis platform to synthesize up to 5 mCi of radiochemically pure 18F-COX-2ib in 4 hours (2% decay-corrected radiochemical yield). In vitro studies demonstrated clear correlation between COX-2 expression and uptake of the tracer. PET imaging of healthy animals confirmed that the molecule is excreted from blood within an hour, mainly through the hepatobiliary excretion pathway. In vivo metabolism data demonstrated that > 95% of the injected radioactivity remains in the form of the parent molecule 1 hour after injection.

To analyze the benefits and prognostic factors after surgical resection of pulmonary metastases from colorectal cancer (CRC).From Jan. 2004 to Jan. 2015, continuous 88 cases diagnosed with pulmonary metastases from CRC, including 15 cases of synchronous metastases and 73 metachronous metastases, were analyzed in the retrospective study.All of these 88 cases underwent curative pulmonary resection including 8 cases of simultaneous surgery. The one-year, three-year and five-year survival of the 88 cases were 93.4%, 60.2% and 35.7%, respectively. 63 patients just have one metastasis, and 25 patients have more than one metastasis. Additionally, the one-year, three-year and five-year survival was 98.1%, 70.2% and 40.3% respectively in one metastasis group, while 80.1%, 37.9% and 22.5% respectively in more than one metastasis group (p = 0.003). DFS of 37 metachronous metastases were equal or greater than 18 months, and DFS of 36 metachronous metastases were less than 18 months. The one-year, three-year and five-year survival was 97.8%, 77.9% and 41.4% respectively in the DFS≥18 month group, while 88.2%, 44.6% and 28.1% respectively in the DFS

Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injury which could be caused by viral, autoimmune, drugs, and so on. Unfortunately, there was no effective therapy available for liver fibrosis in clinic. In this study, we identified the anti-fibrotic effects of 1,7-dihydroxy-3,4,8-trimethoxyxanthone (ZYC-1) on the dimethylnitrosamine (DMN)-induced rat model. ZYC-1 was isolated from Swertia punicea Hemsl and was administrated to DMN-induced rat model. ZYC decreased the hyaluronic acid (HA), type IV collagen (CIV) and hydroxyproline (Hyp) levels and inhibited the expression of α smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-1β). The anti-fibrotic effect of ZYC-1 was also confirmed by Sirius Red staining. Finally, we identified 42 differentially expressed proteins by using proteomics analysis after ZYC-1 treatment, of which 17 were up-regulated and 25 were down-regulated. These Most of the 42 proteins are involved in the oxidative stress pathway, the mitochondrial-mediated apoptotic pathway and the amino acid metabolism pathway. Our study presented the first elucidated mechanisms of xanthone on liver fibrosis in vivo. This study pointed out that ZYC-1 may be used as a lead compound for hepatofibrosis treatment.

The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/β-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used. Gene Ontology Enrichment Analysis and Gene Set Enrichment Analysis have enriched many biological processes and signaling pathways. Both the inhibiting and stimulating Wnt/β-catenin signaling pathways could influence the cell cycle, moreover, reduce the proliferation and survival of U87 glioma cells. However, Affymetrix expression microarray indicated that biological processes and networks of signaling pathways between stimulating and inhibiting the Wnt/β-catenin signaling pathway largely differ. We propose that Wnt/β-catenin signaling pathway might prove to be a valuable therapeutic target for glioma.

The polyphagous mirid bug Apolygus lucorum (Heteroptera: Miridae) has more than 200 species of host plants and is an insect pest of important agricultural crops, including cotton (Gossypium hirsutum) and mungbean (Vigna radiata). Previous field trials have shown that A. lucorum adults prefer mungbean to cotton plants, indicating the considerable potential of mungbean as a trap crop in cotton fields. However, direct evidence supporting the migration of A. lucorum adults from cotton to mungbean is lacking. We developed a DNA-based polymerase chain reaction (PCR) approach to reveal the movement of A. lucorum between neighboring mungbean and cotton fields. Two pairs of PCR primers specific to cotton or mungbean were designed to target the trnL-trnF region of chloroplast DNA. Significant differences in the detectability half-life (DS50) were observed between these two host plants, and the mean for cotton (8.26 h) was approximately two times longer than that of mungbean (4.38 h), requiring weighted mean calculations to compare the detectability of plant DNA in the guts of field-collected bugs. In field trials, cotton DNA was detected in the guts of the adult A. lucorum individuals collected in mungbean plots, and the cotton DNA detection rate decreased successively from 5 to 15 m away from the mungbean-cotton midline. In addition to the specific detection of cotton- and mungbean-fed bugs, both cotton and mungbean DNA were simultaneously detected within the guts of single individuals caught from mungbean fields. This study successfully established a tool for molecular gut-content analyses and clearly demonstrated the movement of A. lucorum adults from cotton to neighboring mungbean fields, providing new insights into understanding the feeding characteristics and landscape-level ecology of A. lucorum under natural conditions.

Constructing genome scale weighted gene association networks (WGAN) from multiple data sources is one of research hot spots in systems biology. In this paper, we employ information entropy to describe the uncertain degree of gene-gene links and propose a strategy for data integration of weighted networks. We use this method to integrate four existing human weighted gene association networks and construct a much larger WGAN, which includes richer biology information while still keeps high functional relevance between linked gene pairs. The new WGAN shows satisfactory performance in disease gene prediction, which suggests the reliability of our integration strategy. Compared with existing integration methods, our method takes the advantage of the inherent characteristics of the component networks and pays less attention to the biology background of the data. It can make full use of existing biological networks with low computational effort.

We have used an insertional mutagenesis approach to generate new C. reinhardtii motility mutants. Of 56 mutants isolated, one is a new allele at the ODA3 locus, called oda3-6. Similar to the previously characterized oda3 alleles, oda3-6 has a slow-jerky swimming phenotype and reduced swimming speed. The oda3-6 mutant fails to assemble the outer dynein arm motor and outer dynein arm-docking complex (ODA-DC) in the ciliary axoneme due to an insertion in the 5' end of the DCC1 gene, which encodes the DC1 subunit of the ODA-DC. Transformation of oda3-6 with the wild-type DCC1 gene rescues the mutant swimming phenotype and restores assembly of the ODA-DC and the outer dynein arm in the cilium. This is the first oda3 mutant to be characterized at the molecular level and is likely to be very useful for further analysis of DC1 function.

Human induced pluripotent stem cells (hiPSCs) may provide potential resource for regenerative medicine research, including generation of insulin-producing cells for diabetes research and insulin production. Testosterone (T) is an androgen hormone which promotes protein synthesis and improves the management of type 2 diabetes in clinical studies. Concurrently, co-existed hyperandrogenism and hyperinsulinism is frequently observed in polycystic ovary syndrome, congenital adrenal hyperplasia and some of Wermer's syndrome. However, the relationship among androgens, insulin and the differentiation of pancreatic β cells is still not fully clear. Here we find that T improves the differentiation efficiency of insulin-producing cells from hiPSCs. The addition of T into routine differentiation formula for pancreatic β cells increases the differentiation efficiency from 12% to 35%. The administration of T promotes the expression of key genes associated with β cells differentiation including NGN3, NEUROD1 and INS. This finding benefits the ongoing process to optimize the differentiation protocol of pancreatic β cells from hiPSCs, and provides some degree of understanding the clinical management of T for type 2 diabetes.

Despite the central role of soil microbial communities in global carbon (C) cycling, little is known about soil microbial community structure and even less about their metabolic pathways. Efforts to characterize soil communities often focus on identifying differences in gene content across environmental gradients, but an alternative question is what genes are similar in soils. These genes may indicate critical species or potential functions that are required in all soils. Here we identified the "core" set of C cycling sequences widely present in multiple soil metagenomes from a fertilized prairie (FP). Of 226,887 sequences associated with known enzymes involved in the synthesis, metabolism, and transport of carbohydrates, 843 were identified to be consistently prevalent across four replicate soil metagenomes. This core metagenome was functionally and taxonomically diverse, representing five enzyme classes and 99 enzyme families within the CAZy database. Though it only comprised 0.4% of all CAZy-associated genes identified in FP metagenomes, the core was found to be comprised of functions similar to those within cumulative soils. The FP CAZy-associated core sequences were present in multiple publicly available soil metagenomes and most similar to soils sharing geographic proximity. In soil ecosystems, where high diversity remains a key challenge for metagenomic investigations, these core genes represent a subset of critical functions necessary for carbohydrate metabolism, which can be targeted to evaluate important C fluxes in these and other similar soils.

Porcine cytomegalovirus (PCMV; genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae) is an immunosuppressive virus that mainly inhibits the immune function of T lymphocytes and macrophages, which has caused substantial damage in the farming industry. In this study, we obtained the miRNA expression profiles of PCMV-infected porcine macrophages via high-throughput sequencing. The comprehensive analysis of miRNA profiles showed that 239 miRNA database-annotated and 355 novel pig-encoded miRNAs were detected. Of these, 130 miRNAs showed significant differential expression between the PCMV-infected and uninfected porcine macrophages. The 10 differentially expressed pig-encoded miRNAs were further determined by stem-loop reverse-transcription polymerase chain reaction, and the results were consistent with the high-throughput sequencing. Gene Ontology analysis of the target genes of miRNAs in PCMV-infected porcine macrophages showed that the differentially expressed miRNAs are mainly involved in immune and metabolic processes. This is the first report of the miRNA transcriptome in porcine macrophages and an analysis of the miRNA regulatory mechanisms during PCMV infection. Further research into the regulatory mechanisms of miRNAs during immunosuppressive viral infections should contribute to the treatment and prevention of immunosuppressive viruses.

Aging may be a risk factor for type 2 diabetes in the elderly. Dietary intervention can affect glucose tolerance in adults, which may be due to body composition and islet cell autophagy. The aim of this study was to determine the effects of various dietary interventions on islet cell autophagy. Pancreatic tissue and blood samples were collected from Sprague Dawley rats (14-16 months old, n = 15 for each group) that received a normal diet (ND), a high-fat diet (HFD), or a calorie-restricted diet (CRD). The body weight (BW), visceral fat, serum lipid levels, fasting serum glucose, insulin levels, and β/α cell area were determined in 14-16-(0-w), 16-18-(8-w), and 18-20(16-w)-month-old rats. Pancreatic islet autophagy (LC3B and LAMP2), AP (Acid Phosphatase) and apoptosis (apoptosis index, AI (TUNEL assay) and cleaved caspase-3) were detected using immunohistochemistry, ELISA and western blot. At 16 weeks, the expressions of LC3B, LAMP2 and AP markedly increased in both the HFD (P

Short-chain fatty acids (SCFAs), produced by anaerobic fermentation of mainly indigestible dietary carbohydrates by gut microbiota, have a profound influence on intestinal function and host energy metabolism. Antibiotics may seriously disturb the balance of fecal SCFAs. To evaluate the impacts of antibiotics on fecal SCFAs produced by gut microbiota, a simple, reproducible and accurate gas chromatography (GC) method, which can simultaneously analyze seven SCFAs in fecal samples, was developed and validated. The ranges of detection and quantitation of the SCFAs reached 0.0868 ~ 0.393 and 0.261 ~ 1.18 μg·mL-1 respectively, in an optimized protocol for SCFAs extraction and analysis that used 10 mL 75% ethanol aqueous solution containing 1% HCl, without ultrasonication. The technique exhibited excellent intra-day (relative standard deviation (RSD) ≤ 2.54%) and inter-day (RSD ≤ 4.33%) precisions for all the SCFAs. Later, we administered broad-spectrum antibiotics, cefdinir or azithromycin to rats and analyzed the alterations in fecal SCFAs. The total amount, types and distribution of nearly all fecal SCFAs were significantly altered during the administration and even after withdrawal of the antibiotics in rats. The effects of cefdinir on the SCFAs were more pronounced than those of azithromycin. Our findings suggest SCFAs may serve as sensitive indicators to monitor the influences of antibiotics on SCFAs originated by intestinal bacteria. Our improved SCFAs analysis method is a potential platform for a standard clinical test of the effects of new antibiotics on SCFAs.

This study investigated the effect of rain-shelter cultivation on the biosynthesis of flavonoids and volatiles in grapes, with an aim of determining whether rain-shelter application could help to improve the sensory attributes and quality of grapes. Vitis vinifera L. Chardonnay grapes, grown in the Huaizhuo basin region of northern China, were selected within two consecutive years. A rain-shelter roof was constructed using a colorless polyethylene (PE) film with a light transmittance of 80%. Results showed that rain-shelter treatment did not affect the accumulation of soluble solids during grape maturation. However, the allocation of assimilated carbon in phenolic and volatile biosynthetic pathways varied significantly, leading to alterations in polyphenolic and volatile profiles. The rain-shelter cultivation enhanced the concentration of flavan-3-ols via the flavonoid-3'5'-hydroxylase (F3'5'H) pathway, but reduced the level of flavonols and flavan-3-ols via the flavonoid-3'-hydroxylase (F3'H) pathway. In addition, the rain-shelter cultivation significantly enhanced the synthesis of fatty acid-derived volatiles, isoprene-derived terpenoids and amino acid-derived branched-chain aliphatics, but led to a decrease in the accumulation of isoprene-derived norisoprenoids and amino acid-derived benzenoids. Principal component analysis revealed some key compounds that differentiated the grapes cultivated under open-field and rain-shelter conditions. Moreover, the effect of the rain-shelter application on the accumulation of these compounds appeared to be vintage dependent. The alteration of their profiles caused by the rain-shelter treatment was significant in the vintage that received higher rainfall, which usually took place in the first rapid growth and veraison phases.

The pine moth Dendrolimus punctatus (Walker) is a common insect pest that confers serious damage to conifer forests in south of China. Extensive physiology and ecology studies on D. punctatus have been carried out, but the lack of genetic information has limited our understanding of the molecular mechanisms behind its development and resistance. Using RNA-seq approach, we characterized the transcriptome of this pine moth and investigated its developmental expression profiles during egg, larval, pupal, and adult stages. A total of 107.6 million raw reads were generated that were assembled into 70,664 unigenes. More than 30% unigenes were annotated by searching for homology in protein databases. To better understand the process of metamorphosis, we pairwise compared four developmental phases and obtained 17,624 differential expression genes. Functional enrichment analysis of differentially expressed genes showed positive correlation with specific physiological activities of each stage, and these results were confirmed by qRT-PCR experiments. This study provides a valuable genomic resource of D. punctatus covering all its developmental stages, and will promote future studies on biological processes at the molecular level.

ObjectivesWe proposed that the severity of ST-segment elevation myocardial infarction (STEMI) could be classified based on pathophysiological changes.MethodsFirst-STEMI patients were classified within hospitalization. Grade 0: no detectable myocardial necrosis; Grade 1: myocardial necrosis without functional and morphological abnormalities; Grade 2: myocardial necrosis with reduced LVEF; Grade 3: reduced LVEF on the basis of cardiac remodeling; Grade 4: mitral regurgitation additional to the Grade-3 criteria.ResultsOf 180 patients, 1.7, 43.9, 26.1, 23.9 and 4.4% patients were classified as Grade 0 to 4, respectively. The classification is an independent predicator of 90-day MACEs (any death, resuscitated cardiac arrest, acute heart failure and stroke): the rate was 0, 5.1, 8.5, 48.8 and 75% from Grade 0 to 4 (p < 0.001), respectively. The Grade-2 patients were more likely to have recovered left ventricular ejection fraction than the Grade-3/4 patients did after 90 days (48.9% vs. 19.1%, p < 0.001). Avoiding complicated quantification, the classification served as a good reflection of infarction size as measured by cardiac magnetic resonance imaging (0 ± 0, 15.68 ± 8.48, 23.68 ± 9.32, 36.12 ± 11.35 and 40.66 ± 14.33% of the left ventricular mass by Grade 0 to 4, P < 0.001), and with a comparable prognostic value (AUC 0.819 vs. 0.813 for infarction size, p = 0.876 by C-statistics) for MACEs.ConclusionsThe new classification represents an easy and objective method to scale the cardiac detriments for STEMI patients.

Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by-association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL) genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO), and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment.

To evaluate the effectiveness of a complex intervention implementing best practice guidelines recommending clinicians screen and counsel young people across multiple psychosocial risk factors, on clinicians' detection of health risks and patients' risk taking behaviour, compared to a didactic seminar on young people's health.Pragmatic cluster randomised trial where volunteer general practices were stratified by postcode advantage or disadvantage score and billing type (private, free national health, community health centre), then randomised into either intervention or comparison arms using a computer generated random sequence. Three months post-intervention, patients were recruited from all practices post-consultation for a Computer Assisted Telephone Interview and followed up three and 12 months later. Researchers recruiting, consenting and interviewing patients and patients themselves were masked to allocation status; clinicians were not.General practices in metropolitan and rural Victoria, Australia.General practices with at least one interested clinician (general practitioner or nurse) and their 14-24 year old patients.This complex intervention was designed using evidence based practice in learning and change in clinician behaviour and general practice systems, and included best practice approaches to motivating change in adolescent risk taking behaviours. The intervention involved training clinicians (nine hours) in health risk screening, use of a screening tool and motivational interviewing; training all practice staff (receptionists and clinicians) in engaging youth; provision of feedback to clinicians of patients' risk data; and two practice visits to support new screening and referral resources. Comparison clinicians received one didactic educational seminar (three hours) on engaging youth and health risk screening.Primary outcomes were patient report of (1) clinician detection of at least one of six health risk behaviours (tobacco, alcohol and illicit drug use, risks for sexually transmitted infection, STI, unplanned pregnancy, and road risks); and (2) change in one or more of the six health risk behaviours, at three months or at 12 months. Secondary outcomes were likelihood of future visits, trust in the clinician after exit interview, clinician detection of emotional distress and fear and abuse in relationships, and emotional distress at three and 12 months. Patient acceptability of the screening tool was also described for the intervention arm. Analyses were adjusted for practice location and billing type, patients' sex, age, and recruitment method, and past health risks, where appropriate. An intention to treat analysis approach was used, which included multilevel multiple imputation for missing outcome data.42 practices were randomly allocated to intervention or comparison arms. Two intervention practices withdrew post allocation, prior to training, leaving 19 intervention (53 clinicians, 377 patients) and 21 comparison (79 clinicians, 524 patients) practices. 69% of patients in both intervention (260) and comparison (360) arms completed the 12 month follow-up. Intervention clinicians discussed more health risks per patient (59.7%) than comparison clinicians (52.7%) and thus were more likely to detect a higher proportion of young people with at least one of the six health risk behaviours (38.4% vs 26.7%, risk difference [RD] 11.6%, Confidence Interval [CI] 2.93% to 20.3%; adjusted odds ratio [OR] 1.7, CI 1.1 to 2.5). Patients reported less illicit drug use (RD -6.0, CI -11 to -1.2; OR 0.52, CI 0.28 to 0.96), and less risk for STI (RD -5.4, CI -11 to 0.2; OR 0.66, CI 0.46 to 0.96) at three months in the intervention relative to the comparison arm, and for unplanned pregnancy at 12 months (RD -4.4; CI -8.7 to -0.1; OR 0.40, CI 0.20 to 0.80). No differences were detected between arms on other health risks. There were no differences on secondary outcomes, apart from a greater detection of abuse (OR 13.8, CI 1.71 to 111). There were no reports of harmful events and intervention arm youth had high acceptance of the screening tool.A complex intervention, compared to a simple educational seminar for practices, improved detection of health risk behaviours in young people. Impact on health outcomes was inconclusive. Technology enabling more efficient, systematic health-risk screening may allow providers to target counselling toward higher risk individuals. Further trials require more power to confirm health benefits.ISRCTN.com ISRCTN16059206.

Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting various stresses in host cells, including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to copper, we generated a copper-resistant strain of Mycobacterium smegmatis, mc2155-Cu from the selection of copper sulfate treated-bacteria. The mc2155-Cu strain has a 5-fold higher resistance to copper sulfate and a 2-fold higher resistance to isoniazid (INH) than its parental strain mc2155, respectively. Quantitative proteomics was carried out to find differentially expressed proteins between mc2155 and mc2155-Cu. Among 345 differentially expressed proteins, copper-translocating P-type ATPase was up-regulated, while all other ABC transporters were down-regulated in mc2155-Cu, suggesting copper-translocating P-type ATPase plays a crucial role in copper resistance. Results also indicated that the down-regulation of metabolic enzymes and decreases in cellular NAD, FAD, mycothiol, and glutamine levels in mc2155-Cu were responsible for its slowing growth rate as compared to mc2155. Down-regulation of KatG2 expression in both protein and mRNA levels indicates the co-evolution of copper and INH resistance in copper resistance bacteria, and provides new evidence to understanding of the molecular mechanisms of survival of mycobacteria under stress conditions.

Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore.Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease.After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p

This study was to evaluate the usefulness of serum thymoglobulin (Tg) in adults to assess iodine status through a 5-year cohort study which was conducted in three regions with different levels of iodine intake: mild deficiency, more than adequate, and excess, from 1999 to 2004 in China. A total of 3099 subjects over 14 years old with normal serum levels of Tg in 1999 were eligible, of whom 2448 were followed in 2004. Serum levels of thyroid hormones and thyroid autoantibodies as well as urine iodine were measured, and B-mode ultrasonography of the thyroid was performed. A general linear model was performed to determine the determinant factors of serum Tg. Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the baseline levels of serum Tg were substantially different (7.5μg/L, 5.9μg/L, and 6.8μg/L respectively, P

Oxidative stress (OS), as a signal of aberrant intracellular mechanisms, plays key roles in maintaining homeostasis for organisms. The occurrence of OS due to the disorder of normal cellular redox balance indicates the overproduction of reactive oxygen species (ROS) and/or deficiency of antioxidants. Once the balance is broken down, repression of oxidative stress is one of the most effective ways to alleviate it. Ongoing studies provide remarkable evidence that oxidative stress is involved in reproductive toxicity induced by various stimuli, such as environmental toxicants and food toxicity. Zearalenone (ZEA), as a toxic compound existing in contaminated food products, is found to induce mycotoxicosis that has a significant impact on the reproduction of domestic animals, especially pigs. However, there is no information about how ROS and oxidative stress is involved in the influence of ZEA on porcine granulosa cells, or whether the stress can be rescued by curcumin. In this study, ZEA-induced effect on porcine granulosa cells was investigated at low concentrations (15 μM, 30 μM and 60 μM). In vitro ROS levels, the mRNA level and activity of superoxide dismutase, glutathione peroxidase and catalase were obtained. The results showed that in comparison with negative control, ZEA increased oxidative stress with higher ROS levels, reduced the expression and activity of antioxidative enzymes, increased the intensity of fluorogenic probes 2', 7'-Dichlorodihydrofluorescin diacetate and dihydroethidium in flow cytometry assay and fluorescence microscopy. Meanwhile, the activity of glutathione (GSH) did not change obviously following 60 μM ZEA treatment. Furthermore, the underlying protective mechanisms of curcumin on the ZEA-treated porcine granulosa cells were investigated. The data revealed that curcumin pre-treatment significantly suppressed ZEA-induced oxidative stress. Collectively, porcine granulosa cells were sensitive to ZEA, which may induce oxidative stress. The findings from this study clearly demonstrate that curcumin is effective to reduce the dysregulation of cellular redox balance on porcine granulosa cells in vitro and should be further investigated for its protective role against ZEA in animals.

The objective of this study was to examine the reflectance of Landsat TM imagery for mapping soil organic Carbon (SOC) content in an Alpine environment. The studied area (ca. 3*104 km2) is the upper reaches of the Heihe River at the northeast edge of the Tibetan plateau, China. A set (105) of topsoil samples were analyzed for SOC. Boosted regression tree (BRT) models using Landsat TM imagery were built to predict SOC content, alone or with topography and climate covariates (temperature and precipitation). The best model, combining all covariates, was only marginally better than using only imagery. Imagery alone was sufficient to build a reasonable model; this was a bit better than only using topography and climate covariates. The Lin's concordance correlation coefficient values of the imagery only model and the full model are very close, larger than the topography and climate variables based model. In the full model, SOC was mainly explained by Landsat TM imagery (65% relative importance), followed by climate variables (20%) and topography (15% of relative importance). The good results from imagery are likely due to (1) the strong dependence of SOC on native vegetation intensity in this Alpine environment; (2) the strong correlation in this environment between imagery and environmental covariables, especially elevation (corresponding to temperature), precipitation, and slope aspect. We conclude that multispectral satellite data from Landsat TM images may be used to predict topsoil SOC with reasonable accuracy in Alpine regions, and perhaps other regions covered with natural vegetation, and that adding topography and climate covariables to the satellite data can improve the predictive accuracy.

Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

Glioblastoma (GBM) is the most common primary brain tumor, accounting for approximately 40% of all central nervous system malignancies. Despite standard treatment consisting of surgical resection, radiotherapy and/or chemotherapy, the prognosis for GBM is poor; with a median survival of 14.6 months. The cancer stem cell or cancer-initiating cell model has provided a new paradigm for understanding development and recurrence of GBM following treatment. Berbamine (BBM) is a natural compound derived from the Berberis amurensis plant, and along with its derivatives, has been shown to exhibit antitumor activity in several cancers. Here, we reported that a novel synthetic Berbamine derivative, BBMD3, inhibits cell viability and induces apoptosis of cancer stem-like cells (CSCs) in a time- and dose-dependent manner when the CSCs from four GBM patients (PBT003, PBT008, PBT022, and PBT030) were cultured. These CSCs grew in neurospheres and expressed CD133 and nestin as markers. Treatment with BBMD3 destroyed the neurosphere morphology, and led to the induction of apoptosis in the CSCs. Induction of apoptosis in these CSCs is dependent upon activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP). MicroRNA-4284 (miR-4284) was shown to be over-expressed about 4-fold in the CSCs following BBMD3 treatment. Furthermore, transfection of synthetic anti-sense oligonucleotide against human miR-4284 partially blocked the anticancer effects of BBMD3 on the GBM derived CSCs. BBMD3 also increased phosphorylation of the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), resulting in an increase expression of phosphorylated c-Jun and total c-Fos; the major components of transcriptional factor AP-1. The JNK-c-Jun/AP-1 signaling pathway plays an important role in the induction of apoptosis in response to UV irradiation and some drug treatments. Targeting glioblastoma stem-like cells with BBMD3 is therefore novel, and may have promise as an effective therapeutic strategy for treating GBM patients.

Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease, which has been continuously prevalent in Asia in recent years. In children, severe cases can lead to death, and no prophylactic or therapeutic measures against EV71 infection are available. The 3C proteases of EV71 play an important role in viral replication and are an ideal drug target. In previous work, we resolved the crystal structure for EV71 3Cpro. In this report, we took advantage of the automated docking program AutoDock 4.0 to simulate EV71 3Cpro-ligand conformation. 7-hydroxyflavone (HF) and its phosphate ester(FIP) were predicted to bind with EV71 3Cpro.In an in vitro protease inhibition assay, FIP inhibited EV71 3Cpro protease activity. Both flavones were highly active against EV71, protecting cells from EV71 infection. Replication of viral RNA and formation of EV71 plaque were all strongly inhibited in cells. These results indicated that HF and FIP may serve as potential protective agents in the treatment of patients with chronic EV71 infection.

BACKGROUND: To adapt to extreme environments, the crustacean Artemia has evolved two alternative reproductive pathways. During ovoviviparous (direct) development, nauplius larvae are produced. In contrast, Artemia females release encysted diapause embryos (cysts) via the oviparous pathway. To date, the cellular mechanisms that regulate stress resistance of Artemia remain largely unknown. Ste20-like kinase (SLK) participates in multiple biological processes, including stress responses, apoptosis, and cell cycle progression. PRINCIPAL FINDING: We isolated and characterized a member of the SLK superfamily termed ArSLK from Artemia parthenogenetica. The ArSLK gene is transcribed throughout both ovoviviparous and oviparous development; however, the protein is located mainly in the nuclei of stress-resistant diapause cysts, unlike the nauplii and nauplius-destined embryos where it is cytoplasmic. Interestingly, exposure of nauplii to heat shock, acidic pH, and UV irradiation induced the translocation of ArSLK from cytoplasm to nucleus. This translocation was reversed following stress removal. Moreover, under physiologically-stressful conditions, the nauplius larvae produced by adults after gene knockdown of endogenous ArSLK by RNAi, lost the ability of free-swimming much earlier than those of control larvae from females injected with GFP dsRNA. CONCLUSIONS/SIGNIFICANCE: Taken together, this study demonstrated that trafficking of ArSLK between the cytoplasm and the nucleus participates in regulating the stress resistance of Artemia. Our findings may provide significant insight into the functions of members of the SLK superfamily.

The relationship between obesity and cardiovascular disease (CVD) remains unclear. This study aims to describe the relationship between arterial stiffness and obesity in order to investigate the effects of obesity on CVD.We collected data from 5,158 individuals over 40 years of age from a cross-sectional study in Nanjing, China. Anthropometric, demographic, hemodynamic measurements and arterial stiffness measured through brachial-ankle pulse wave velocity (baPWV) were obtained. Subjects were grouped by body mass index (BMI), waist circumference (WC) and visceral adiposity index (VAI), a sex-specific index based on BMI, WC, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C).The multivariate regression analysis revealed a negative but weak effect of BMI (β = -0.047, P0.05), it was still obtained between baPWV and VAI quartile (P0.05). However, baPWV significantly increased across groups with higher VAI categories even in the same metabolic category (P