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IntroductionThe natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software.MethodsA total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFRResultsPatients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (pConclusionsMild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up.Trial registrationClinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

ObjectiveMinimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage.MethodsThe blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group.ResultsA total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342).ConclusionsOur study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results.

Base flow, as an important component of runoff, is the main recharge source of runoff during the dry period, especially in the Yellow River Basin located in a semiarid area. However, the process of obtaining base flow has great uncertainty when considering hydrological simulations. Thus, in this study, a three-step framework is proposed, i.e., the particle swarm optimization (PSO) algorithm is used to calibrate model parameters under different subbasin partitioning schemes; then, the hydrograph separation (HYSEP), Improved United Kingdom Institute of Hydrology (IUKIH) and Lyne and Hollick filter (Lyne-Hollick) methods are used to separate the baseflow from the total runoff process, thereby exploring the uncertainty impacts of baseflow segmentation methods on the hydrological simulation process. The subsample-variance-decomposition method is used to quantify the independent and interactive uncertainty in the hydrological simulation process. The results show that the Topmodel model can be better applied to the source area of the Yellow River (the KGE values in the Sub5, Sub13, Sub21, Sub29, Sub37 and Sub13 scenarios were 0.91 and 0.65, 0.94 and 0.86, 0.94 and 0.88, 0.92 and 0.82, 0.95 and 0.89, and 0.92 and 0.83, respectively). The subbasin division uncertainty had less impact on simulated streamflow during the dry season and had a significant impact in the wet season, such as, the subbasin division uncertainty caused the difference between the median of the simulated streamflow to be as high as 213.09 m3/s in August but only 107.19 m3/s in January; Meanwhile, the baseflow segmentation method uncertainty has a significant impact on the annual mean streamflow values under different subbasin segmentation schemes. In addition, the baseflow values estimated by the Lyne-Hollick and HYSEP methods were obviously higher than those estimated by the IUKIH method during the wet season. The uncertainty influence of subbasin partitioning schemes and baseflow segmentation methods had significant differences on hydrological processes in different periods. The uncertainty influence of subbasin partitioning schemes was dominant in the dry season, accounting for 86%, and the baseflow segmentation methods took second place, accounting for approximately 12%. In the wet season, the uncertainty influence of the baseflow segmentation methods was gradually weakened, which may have been due to the uncertainty influence of the hydrological model. These results provide a reference for the calibration and validation of hydrological model parameters using baseflow components.

This study explored the contexts in which native Japanese listeners have difficulty identifying prosodic focus. Using a 4AFC identification task, we compared native Japanese listeners' focus identification accuracy in different lexical accent × focus location conditions using resynthesised speech stimuli, which varied only in fundamental frequency. Experiment 1 compared the identification accuracy in lexical accent × focus location conditions using both natural and resynthesised stimuli. The results showed that focus identification rates were similar with the two stimulus types, thus establishing the reliability of the resynthesised stimuli. Experiment 2 explored these conditions further using only resynthesised stimuli. Narrow foci bearing the lexical pitch accent were always more correctly identified than unaccented ones, whereas the identification rate for final focus was the lowest among all focus locations. From these results, we argue that the difficulty of focus perception in Japanese is attributed to (i) the blocking of PFC by unaccented words, and (ii) similarity in F0 contours between lexical pitch accent and narrow focus, including in particular the similarity between downstep and PFC. Focus perception is therefore contingent on other concurrent communicative functions which may sometimes take precedence in a +PFC language.

Climate warming accelerates the hydrological cycle, especially in high-latitude and high-altitude areas. The increase in temperature will increase the amount of snow and glacier melting and change the runoff, which will affect the operations of cascade reservoirs significantly. Therefore, taking the upper reaches of the Yellow River with an alpine climate as an example, we propose an improved SIMHYD-SNOW, which considers the snowmelt runoff process. The impacts of climate changes on the runoff process were revealed based on the SIMHYD-SNOW model using the precipitation and temperature data predicted by the SDSM model. A model for the maximum power generation of the cascade reservoirs in the upper reaches of the Yellow River was constructed to explore the impacts of climate changes on the inter-annual and intra-annual hydropower generation of the cascade reservoirs at different periods in the future. The results show that climate change has changed the spatial and temporal allocation of water resources in this area. The future runoff will decrease during the flood period (July to September) but increase significantly during the non-flood period. The inter-annual and intra-annual hydropower generation under the RCP8.5 climate change scenario is significantly lower than the RCP2.6 and RCP4.5 climate change scenarios, and as the CO2 emission concentration increases, this gap increases significantly. This study can provide technical references for the precise formulation of water resources management under climate change.

In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic aspects of STH infections with a scarcity of information on the efficacy of deworming treatment. The present study consisted of 2 phases: a cross-sectional phase on current epidemiological status and risk factors of STH infections and a longitudinal study over 6 weeks on triple dose albendazole efficacy against STH infections. A total of 253 participants were recruited at baseline and a pre-tested questionnaire was administered to obtain information on socio-demographics, environmental and behavioural risk factors. Stool samples were evaluated using a modified Kato-Katz technique. Cure rate (CR) and egg reduction rate (ERR) were assessed at 3 weeks following a 3-day course of 400mg albendazole treatment and infection status were observed again at 6 weeks. Baseline positivity of trichuriasis, ascariasis and hookworm infections were 56.1%, 11.9% and 20.2%, respectively. Multivariate analysis showed age below 18 years old (P = 0.004), without latrine in house (P = 0.042) and indiscriminate defecation (P = 0.032) were associated with STH infections. In the longitudinal study (N = 89), CR for trichuriasis was 64.6%, while CR of 100% was observed for both ascariasis and hookworm. ERR was above 90% for all three STH species. A rapid increased of Trichuris trichiura egg output was observed at 6 weeks. In conclusion, STH infections are highly prevalent among indigenous communities. Children and teenagers, poor sanitation and hygiene behaviour were determinants for STH infections. Triple dose albendazole is found to be efficacious against Ascaris lumbricoides and hookworm infections but has moderate curative effect with high ERR against T. trichiura. Although triple dose albendazole regimen has logistic challenges and may not be a routine option, consideration of this treatment regime may still be necessary in selective communities to reduce high intensity of T. trichiura infection.

Natural resources are scarce in the Loess Plateau, and the ecological environment is fragile. Sustainable development requires special attention to resource and environmental carrying capacity (RECC). This study selected 24 representative cities in five natural areas of the Loess Plateau; used the entropy-weight-based TOPSIS method to evaluate and analyze the RECC of each city and region from 2013 to 2018; established a diagnosis model to identify the obstacle factors restricting the improvement of RECC; and constructed the theoretical framework of the RECC system mechanism. The results show that the RECC of the Loess Plateau is increasing in general but is relatively small. The environmental and social subsystems have the highest and lowest carrying capacities, respectively. There is an evident contradiction between economic development and the environment. Population density, investment in technological innovation, per capita sown area, and per capita water resources are the main obstacles affecting the improvement of RECC in the Loess Plateau. Such evaluations and diagnoses can support ecological civilization and sustainable development.

Current image encryption methods have many shortcomings for the medical image encryption with high resolution, strong correlation and large storage space, and it is difficult to obtain reliable clinically applicable medical images. Therefore, this paper proposes a medical image encryption algorithm based on a new five-dimensional three-leaf chaotic system and genetic operation. And the dynamic analysis of the phase diagram and bifurcation diagram of the five-dimensional three-leaf chaotic system selected in this paper is carried out, and NIST is used to test the randomness of its chaotic sequence. This algorithm follows the diffusion-scrambling framework, especially using the principle of DNA recombination combined with the five-dimensional three-leaf chaotic system to generate a chaotic matrix that participates in the operation. The bit-level DNA mutation operation is introduced in the diffusion, and the scrambling and diffusion effects have been further improved. Algorithm security and randomness have been enhanced. This paper evaluates the efficiency of this algorithm for medical image encryption in terms of security analysis and time performance. Security analysis is carried out from key space, information entropy, histogram, similarity between decrypted image and original image, PSNR, correlation, sensitivity, noise attack, cropping attack and so on. Perform time efficiency analysis from the perspective of time performance. The comparison between this algorithm and the experimental results obtained by some of the latest medical image encryption algorithms shows that this algorithm is superior to the existing medical image encryption algorithms to a certain extent in terms of security and time efficiency.

BACKGROUND:Fixed-combination (FC) therapy is used in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients who require more than one medication to reach their target intraocular pressure (IOP). Currently, there are several FC therapies available for the treatment of glaucoma. The FC of latanoprost/timolol (LTFC) is a commonly used FC. Here, we conducted systematic review to compare the IOP-lowering effects of LTFC with other FCs for patients with POAG and OHT. MATERIALS AND METHODS:We searched PubMed, EMBASE, the Cochrane Library, and Web of Science for randomized-controlled clinical trials and cross-over studies. The outcomes were mean IOP and IOP fluctuation after one month of treatment. Meta-analysis was carried out using RevMan (version 5.1) software. After conducting meta-analyses, we rated the quality of each meta-analysis as high, moderate, low, or very low using the "GRADE" system. RESULTS:We included 16 trials in this meta-analysis. Moderate-quality meta-analysis showed that LTFC had a comparable mean IOP to that of a fixed combination of travoprost and timolol (TTFC) [mean difference (MD): 0.07 mmHg] and a fixed combination of dorzolamide and timolol (DTFC) [MD: -0.31 mmHg], and it also had a comparable IOP-fluctuation effect compared to that of TTFC [MD: 0.13 mm Hg] and DTFC [MD: 0.25 mmHg]. Compared to the fixed combination of bimatoprost and timolol (BiTFC), moderate-quality evidence showed a higher mean IOP in the LTFC group [MD 0.76 mmHg], whereas low-quality meta-analysis showed higher IOP fluctuation [MD 1.09 mmHg] in the LTFC group. CONCLUSIONS:LTFC is as effective as TTFC and DTFC, but worse than BiTFC in controlling mean IOP and IOP fluctuation for POAG or OHT patients. The quality of our meta-analyses was assessed as moderate, with the exception of one low-quality analysis that compared the IOP fluctuation of LTFC and BiTFC.

Building a density map over large areas could provide essential information of land development intensity and settlement condition. It is crucial for supporting studies and planning of human settlement environment. The Global Human Settlement Layer (GHSL) is a comprehensive data set of mapping human settlement at a global scale, which was produced by the Joint Research Centre (JRC), European Commission. The built-up density is an important layer of GHSL data set. Currently, the validation of the GHSL built-up area products was preliminarily conducted over the United States and European countries. However, as a typical East Asian region, China is quite different from the United States, Europe, and other regions in terms of building forms and urban layouts. Therefore, it is necessary to perform an accuracy assessment of GHSL data set in Asian countries like China. With individual building footprint data of 20 typical cities in China, this paper presents our effort to validate the GHSL built-up area products. The aggregation mean and neighborhood search based algorithms are adopted for matching building footprint data and the GHSL products, through the regression analysis at per-pixel level, the building density map in raster format are generated as validation data. The accuracy index of GHSL built-up area was calculated for the study areas, and the validation methods were explored for GHSL built-up products at large scale. The results show that the built-up layer aggregated by the building footprint have the highest correlation with the coarse resolution GHSL built-up products, but GHSL tends to underestimate the building density of low-density areas and overestimate the areas with high density. This study suggests that GHSL built-up area products in 20 representative Chinese cities of China could provide quantitative information about built-up areas, but the product accuracy still need to be improved in the regions with heterogeneous formations of human settlements like China. There is a big picture of mapping high accuracy built-up density of China with the training data set acquired by the study.

Sri Lanka's community forestry (CF) program emerged in the early 1980s following a global trend to conserve forest resources and provide benefits to the local community. However, very little is known about the effect of CF on forest resources. We assess the impacts of CF on forest conditions of semi-mixed evergreen forest in the intermediate zone of Sri Lanka using the before-after control-impact method. The study examines tree density, regeneration, woody species diversity, and evidence of disturbance as parameters to analyze the impact of the CF program. Data are analyzed using the difference in differences approach. The results show that the CF program has increased seedling and sapling density to a significant degree and reduced human disturbances. A major contribution of the CF program is that it was found to reduce invasive species and forest fires. The program reduced the amount of invasive species up to six times less than previous. The findings revealed that the impact of CF on forests may vary depending on pre-existing forest conditions, length of period to implement, perception, and decisions by local people. Community understanding and decision-making, in tandem with government policy, will weigh heavily on its future effectiveness.

During the past decades, heavy metal pollution in agricultural soil and its impact on human health have been becoming one of the most important global environmental problems. In this research, heavy metal (Cu, Pb, Zn, Cr, Cd, Ni, As, Hg) concentrations were measured for four hundred and two soil samples collected from agricultural area within the Guangzhou-Foshan urban zone. Soil heavy metal pollution was evaluated used geoaccumulation index and potential ecological risk index. The dose response model proposed by the USEPA was used to estimate the potential health risk caused by heavy metals in agricultural soil. The results showed that: 1) Cd and Hg were the main heavy metal pollutants in agricultural soil of the study area. 89.1% and 93.3% of total soil samples suffered medium to heavy potential ecological risk caused by Cd and Hg, respectively. 2) The THI and TCR were respectively greater than 1.0 and 1.0×10-4, indicating that heavy metals in agricultural soil were likely to constitute non-carcinogenic and carcinogenic risks, both of which were mainly brought by product consumption, to the public in the study area. The non-carcinogenic risks were mainly caused by Cr and As, while the carcinogenic risks were mainly from Cr, Cd, and As.

Bread wheat (AABBDD) originated from the diploid progenitor Triticum urartu (AA), a relative of Aegilops speltoides (BB), and Ae. tauschii (DD). The DREB1 transcriptional factor plays key regulatory role in low-temperature tolerance. The modern breeding strategies resulted in serious decrease of the agricultural biodiversity, which led to a loss of elite genes underlying abiotic stress tolerance in crops. However, knowledge of this gene's natural diversity is largely unknown in the genome donor species of wheat. We characterized the dehydration response element binding protein 1 (DREB1) gene-diversity pattern in Ae. speltoides, Ae. tauschii, T. monococcum and T. urartu. The highest nucleotide diversity value was detected in Ae. speltoides, followed by Ae. tauschii and T. monococcum. The lowest nucleotide diversity value was observed in T. urartu. Nucleotide diversity and haplotype data might suggest no reduction of nucleotide diversity during T. monococcum domestication. Alignment of the 68 DREB1 sequences found a large-size (70 bp) insertion/deletion in the accession PI486264 of Ae. speltoides, which was different from the copy of sequences from other accessions of Ae. speltoides, suggesting a likely existence of two different ancestral Ae. speltoides forms. Implication of sequences variation of Ae. speltoides on origination of B genome in wheat was discussed.

Quantitative analysis of the contribution rate of China's hydraulic science and technology and analysis of the underlying reasons behind changes provide an important foundation upon which the government can formulate water policies. This paper abandons the assumption of a scale economy and separates the changes of benefits brought about by the scale from scientific and technological progress, thus changing the C-D production function from linear to nonlinear. Based on a feedforward neural network, it calculates the coefficient of the output elasticity, the economic contribution rate of China's hydraulic science and technology and the scale economies for each year using relevant data from 1981 to 2016. The results show that (1) the average contribution rate of capital investment from 1981 to 2016 was 47.3%, and the average contribution rate of labor from 1981 to 2016 was 9.1%. It is not obvious that the significant increase in the labor force has contributed to the growth of China's water conservancy industry. (2) The average contribution rate of scale economies in 1981-2016 was 26.7%, and the contribution rate of scale economies is negatively correlated with the capital contribution rate. (3) The average contribution rate of China's hydraulic science and technology was 43.6% from 1981 to 2016, and the average contribution rate of the total factor productivity after removing scale economies from 1981 to 2016 was 16.9%. During the period of the 6th Five-Year Plan(1981~1985), the contribution rate of water conservancy science and technology was relatively high. Since that time, it has remained at 40%. In recent years, as water conservancy reforms in key areas have made positive progress, scientific and technological progress has increased the growth of water conservancy benefits annually.

BACKGROUND:The background advertisement exposure parameters (BAEP) forms a premise for sponsorship negotiation and the basis for estimating the sponsorship value of background advertising. Prediction of the BAEP has a great contribution to the sporting events organizers and sponsors in terms of negotiating, decision-making for bidding, and income-generating. METHODS:Virtual Reality (VR), technology was utilized to construct a virtual three-dimensional model of the sports venue and simulate the telecast of the event. Based on VR technology and computer graphics theory, a pre-event prediction method for estimating the background advertisement exposure parameters of sporting events was put forward. The pre and post measures of the thirty BAEP of televised football games were compared to verify the effectiveness of the prediction method. RESULTS:There was no significant difference between the pre- and post-measurement results for the same football game. The pre- and post-measurement results of the thirty BAEP of televised football games were tightly matched. CONCLUSIONS:Using the prediction method can predict the BAEP of televised football games effectively and overcomes the shortcomings of current prediction methods that inhibits the effectiveness of the prediction of exposure parameters due to changes such as the type of the sporting events, the size of the sports venue, the layout of the background advertisements, and the placement of the television cameras, etc.

Background and objectiveAction observation training (AOT) has been used as a new intervention for improving upper limb motor functions in people with stroke. This systematic review and meta-analysis aims to investigate the effects of AOT on improving upper limb motor functions in people with stroke.MethodsWe searched ten electronic databases to identify randomized controlled trials (RCTs) about the effects of AOT on upper limb motor functions in stroke survivors. Methodological quality of included studies was assessed by the Risk of Bias Tool in the Cochrane Handbook for Systematic Reviews of Interventions. A random-effects meta-analysis was performed by pooling the standardized mean difference (SMD) of upper limb motor outcomes.ResultsSeven studies of 276 participants with stroke were included. Meta-analysis showed a significant effect favoring AOT on improving upper limb motor functions in patients with stroke [SMD = 0.35, 95% confidence interval [CI], 0.10 to 0.61, I2 = 10.14%, p = 0.007].ConclusionsAOT appears to be an effective intervention for improving the upper limb motor functions in people after stroke. Further studies need to investigate the neural mechanism underlying the effects of AOT.

Coxsackievirus A2 (CV-A2) has emerged as an important etiological agent in the hand, foot, and mouth disease and herpangina pathogen spectrum because of its high global prevalence. In the present study, we investigated the evolutionary dynamics of CV-A2 circulating in China. We analyzed a total of 163 entire VP1 sequences of CV-A2, including 74 sequences generated from the present study and 89 sequences collected from the GenBank database. Phylogenetic analysis based on the entire VP1 nucleotide sequences confirmed the persistent circulation of the predominant genotype D in mainland of China since 2008. Cluster analysis grouped the sequences into two distinct clusters, clusters 1 and 2, with most grouped under cluster 2. After 2012, cluster 1 was gradually replaced by cluster 2. Results of Bayesian Markov chain Monte Carlo analysis suggested that multiple lineages of genotype D were transmitted in mainland of China at an estimated evolutionary rate of 6.32×10(-3) substitutions per site per year, which is consistent with the global evolutionary rate of CV-A2 (5.82×10(-3) substitutions per site per year). Continuous transmission and evolution of CV-A2 resulted in the genetic polymorphism.

Dalangtan Playa is the second largest salt playa in the Qaidam Basin, north-western China. The hyper saline deposition, extremely arid climate and high UV radiation make Dalangtan a Mars analogue both for geomorphology and life preservation. To better understand microbial life at Dalangtan, both culture-dependent and culture-independent methods were examined and simultaneously, environment conditions and the evaporitic mineral assemblages were investigated. Ten and thirteen subsurface samples were collected along a 595-cm deep profile (P1) and a 685-cm deep profile (P2) respectively, and seven samples were gathered from surface sediments. These samples are composed of salt minerals, minor silicate mineral fragments and clays. The total bacterial cell numbers are (1.54±0.49) ×10(5) g-1 for P1 and (3.22±0.95) ×10(5) g-1 for P2 as indicated by the CAtalyzed Reporter Deposition- Fluorescent in situ Hybridization (CARD-FISH). 76.6% and 75.7% of the bacteria belong to Firmicutes phylum respectively from P1 and P2. In total, 47 bacteria and 6 fungi were isolated from 22 subsurface samples. In contrast, only 3 bacteria and 1 fungus were isolated from 3 surface samples. The isolated bacteria show high homology (≥97%) with members of the Firmicutes phylum (47 strains, 8 genera) and the Actinobacteria phylum (3 strains, 2 genera), which agrees with the result of CARD-FISH. Isolated fungi showed ≥98% ITS1 homology with members of the phylum Ascomycota. Moisture content and TOC values may control the sediments colonization. Given the deliquescence of salts, evaporites may provide refuge for microbial life, which merits further investigation. Halotolerant and spore-forming microorganisms are the dominant microbial groups capable of surviving under extreme conditions. Our results offer brand-new information on microbial biomass in Dalangtan Playa and shed light on understanding the potential microbial life in the dried playa or paleo-lakes on Mars.

Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.

Computational prediction of RNA-protein complex 3D structures includes two basic steps: one is sampling possible structures and another is scoring the sampled structures to pick out the correct one. At present, constructing accurate scoring functions is still not well solved and the performances of the scoring functions usually depend on used benchmarks. Here we propose a pair-conformation-dependent scoring function, 3dRPC-Score, for 3D RNA-protein complex structure prediction by considering the nucleotide-residue pairs having the same energy if their conformations are similar, instead of the distance-only dependence of the most existing scoring functions. Benchmarking shows that 3dRPC-Score has a consistent performance in three test sets.

There is a need to develop better methods for epitope mapping and/or identification of antibody-recognizing motifs. Here, we describe improved biosynthetic peptide (BSP) method using a newly developed plasmid pXXGST-3 as vector, which has a viral E7 gene in the cloning sites of pXXGST-1. It is crucial to employ pXXGST-3 instead of pXXGST-1, since it makes use of the BSP method simpler and easier to perform, and more cost-effective for epitope mapping. These merits are embodied in two aspects: i) convenient recovery of double enzyme-digested product due to the existence of 315 bp inserted between BamH I and Sal I sites, and thus greatly reducing the production of self-ligation clones, and ii) no longer requiring control protein when screening recombinant (r-) clones expressing 8/18mer peptides by running polyacrylamide gel electrophoresis. The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. This improved GST188-BSP method provides a powerful alternative tool for epitope mapping.

1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) has been widely studied as a neurotoxic substance, however, only few reports have explored its effect on carcinogenicity. Since the aberrant modification of DNA methylation occurs very early in almost all human cancers, the focus of this study is to assess the carcinogenicity of TaClo by characterizing alterations of the epigenetic state, specifically, DNA methylation, upon exposure to TaClo in a HEK 293 model cell line. Our results suggest that TaClo could induce global DNA hypomethylation and transcriptional repression of critical tumor suppressor genes by increasing their promoter methylation. Enhanced cell proliferation, migration and anchorage independent growth were observed in cells exposed to TaClo. Our study highlights the epigenetic toxicity of TaClo, which contributes to its carcinogenicity by altering the DNA methylation status.

The Low-profile Visualized Intraluminal Support (LVIS) device is a new generation of self-expanding braided stent recently introduced in China for stent assisted coiling of intracranial aneurysms. The aim of our study is to evaluate the feasibility, safety, and efficacy of the LVIS device in reconstructive treatment of vertebral artery dissecting aneurysms (VADAs).We retrospectively reviewed the neurointerventional database of our institution from June 2014 to May 2016. Patients who underwent endovascular treatment of VADAs with LVIS stents were included in this study. Clinical presentation, aneurysmal characteristics, technical feasibility, procedural complications, and angiographic and clinical follow-up results were evaluated.38 patients with VADAs who underwent treatment with LVIS stent were identified, including 3 ruptured VADAs. All VADAs were successfully treated with reconstructive techniques including the stent-assisted coiling (n = 34) and stenting only (n = 4). Post-procedural complications developed in 3 patients (7.9%) including two small brainstem infarctions and one delayed thromboembolic event. Complications resulted in one case of minor permanent morbidity (2.6%). There was no procedure-related mortality. The follow-up angiogram was available in 30 patients at an average of 8.3 months (range, 2 to 30 months), which revealed complete occlusion in 23 patients (76.7%), residual neck in five patients (16.7%), and residual sac in two patients (6.7%). The follow-up of 25 aneurysms with incomplete immediate occlusion revealed 22 aneurysms (88%) with improvement in the Raymond class. One aneurysm (3.3%) showed recanalization and required retreatment. Clinical followed-up at 5-28 months (mean 14.1 months) was achieved in 36 patients because two patients died of pancreatic cancer and basal ganglia hemorrhage, respectively. No new neurologic deterioration or aneurysm (re)bleeding was observed.Our preliminary experience with reconstruction of VADAs with the LVIS device demonstrates that this treatment approach is feasible with good short-term angiographic and clinical outcomes. Long-term and larger cohort studies are necessary to determine long-term outcomes of this therapy.

White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study. Neuropsychological measures and diffusion tensor imaging (DTI) data were acquired from each subject and tract-based spatial statistics (TBSS) was implemented. It was found that both aMCI groups showed significantly reduced fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) than NC. It was also identified that, as compared to aMCI-m, aMCI-s showed significantly decreased FA in the left SLF, left uncinate fasciculus (UF) and left inferior longitudinal fasciculus (ILF), while significantly increased FA in the left anterior thalamic radiation (ATR). The correlation analysis showed that FA values in the regions with group difference were significantly correlated with cognitive functions as measured by Boston naming test and trail making test. These results suggested that the variations of aMCI may be differentiated by FA indexes and DTI may help to understand why specific signs and symptoms occur in patients.

Cancer is one of the most common causes of deaths worldwide. Herein, we report an efficient natural anticancer glucan (CVG) extracted from Coriolus Versicolar (CV). CVG was extracted by the hot water extraction method followed by ethanol precipitation and purified using gas exclusion chromatography. Structural analysis revealed that CVG has a linear α-glucan chain composed of only (1→ 6)-α-D-Glcp. The antitumor activity of CVG on Sarcoma-180 cells was investigated in vitro and in vivo. Mice were treated with three doses of CVG (40, 100, 200 mg/kg body weight) for 9 days. Tumor weight, relative spleen, thymus weight, and lymphocyte proliferation were studied. A significant increase (P< 0.01) in relative spleen and thymus weight and a decrease (P< 0.01) in tumor weight at the doses of 100 and 200 mg/kg were observed. The results obtained demonstrate CVG has antitumor activity towards Sarcoma-180 cells by its immunomodulation activity.

Sludge dewatering can effectively reduce the volume and mass of sludge for subsequent treatment and disposal. The work validated the potential of Fenton's reagent combined with dodecyl dimethyl benzyl ammonium chloride (DDBAC) in improving sludge dewaterability and proposed the mechanism of joint conditioning. The composite conditioner dosage was optimized using response surface methodology. Results indicated the good conditioning capability of the composite conditioners. The optimum dosages for H2O2, Fe2+, and DDBAC were 44.6, 39.6, and 71.0 mg/g, respectively, at which a sludge cake water content of 59.67% could be achieved. Moreover, a second-order polynomial equation was developed to describe the behavior of joint conditioning. Analysis of the reaction mechanism showed that Fenton oxidation effectively decomposed extracellular polymeric substance (EPS), including loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS), into dissolved organics, such as proteins and polysaccharides. The process facilitated the conversion of the bound water into free water. Furthermore, DDBAC further released the bound water through solubilization of TB-EPS and LB-EPS after the Fenton reaction. The bound water content of the sludge conditioned with Fenton's reagent decreased from 3.15 to 1.36 g/g and further decreased to 1.08 g/g with the addition of DDBAC. High-performance liquid chromatography analysis verified that the composite conditioning could oxidize and hydrolyze EPS into low-molecular-mass organics (e.g., formic and acetic acid), thereby facilitating the release of bound water.

Chronic lead (Pb) exposure causes cognitive deficits. This study aimed to explore the neuroprotective effect and mechanism of β-asarone, an active component from Chinese Herbs Acorus tatarinowii Schott, to alleviate impairments of spatial memory and synaptogenesis in Pb-exposed rats. Both Sprague-Dawley developmental rat pups and adult rats were used in the study. Developmental rat pups were exposed to Pb throughout the lactation period and β-asarone (10, 40mg kg-1, respectively) was given intraperitoneally from postnatal day 14 to 21. Also, the adult rats were exposed to Pb from embryo stage to 11 weeks old and β-asarone (2.5, 10, 40mg kg-1, respectively) was given from 9 to 11 weeks old. The level of β-asarone in brain tissue was measured by High Performance Liquid Chromatography. The Morris water maze test and Golgi-Cox staining method were used to assess spatial memory ability and synaptogenesis. The protein expression of NR2B subunit of NMDA receptor, Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and Wnt family member 7A (Wnt7a) in hippocampus, as well as mRNA expression of Arc/Arg3.1 and Wnt7a, was also explored. We found that β-asarone could pass through the blood brain barrier quickly. And β-asarone effectively attenuated Pb-induced reduction of spine density in hippocampal CA1 and dentate gyrus areas in a dose-dependent manner both in developmental and adult rats, meanwhile the Pb-induced impairments of learning and memory were partially rescued. In addition, β-asarone effectively up-regulated the protein expression of NR2B, Arc and Wnt7a, as well as the mRNA levels of Arc/Arg3.1 and Wnt7a, which had been suppressed by Pb exposure. The results suggest the neuroprotective properties of β-asarone against Pb-induced memory impairments, and the effect is possibly through the regulation of synaptogenesis, which is mediated via Arc/Arg3.1 and Wnt pathway.

Transformation with an isopentenyl transferase (ipt) gene controlling cytokinin (CK) synthesis has been shown to enhance plant drought tolerance. The objective of this study was to identify differentially-expressed genes (DEGs) in creeping bentgrass (Agrostis stolonifera) overexpressing ipt compared to non-transgenic plants. The ipt transgene was controlled by a senescence-activated promoter (SAG12). Both a null transformed line (NT) and SAG12-ipt plants were exposed to drought stress in an environmentally-controlled growth chamber until the soil water content declined to approximately 5% and leaf relative water content declined to 47%, which were both significantly below the well-watered controls. RNA was extracted from leaf samples of both well-watered and drought-stressed plants. Eight sets of subtractive hybridizations were performed for detection of up-regulated and down-regulated genes due to the presence of the transgene and due to drought stress in both NT and transgenic plants. Sequencing analysis revealed the identity of 252 DEGs due to either the transgene and drought stress. Sequencing analysis of 170 DEGs identified genes encoding for proteins that were related to energy production, metabolism, stress defense, signaling, protein synthesis and transport, and membrane transport could play major roles in the improved drought tolerance by overexpressing ipt in creeping bentgrass.

Refractory surface of wound and dermal chronic ulcer are largely attributed to poor neovascularization. We have previously shown that E2F1 suppresses VEGF expression in the ischemic heart, and that genetic deletion of E2F1 leads to better cardiac recovery. However, whether E2F1 has a role in dermal wound healing is currently not known.Skin wounds were surgically induced in E2F1-null (E2F1-/-) mice and WT littermates. E2F1-/- displayed an accelerated wound healing including wound closure, dermal thickening and collagen deposition, which was associated with an increased endothelial cell proliferation and greater vessel density in the border zone of the wound. Furthermore, more macrophages were recruited to the skin lesions and the level of VEGF expression was markedly higher in E2F1-/- than in WT mice.E2F1 hinders skin wound healing by suppressing VEGF expression, neovascularization, and macrophage recruitment. Strategies that target E2F1 may enhance wound healing.

PURPOSE:To prospectively evaluate the diagnostic performance of coronary CT angiography (CCTA) for the assessment of coronary stenosis in a calcified plaque, by using conventional coronary angiography (CAG) as a standard reference. MATERIALS AND METHODS:Eight hundred and ninety-four patients were known to have or have been suspicious of having coronary artery disease, underwent CCTA and conventional coronary angiography (CAG). All the images acquired were assessed. The calcified plaque in CCTA was classified into four types (I-IV) according to the ratio of calcified plaque volume to vessel circumference (RVTC). Overall diagnostic accuracy was made under receiver operating characteristic curve (AUC) analysis. CAG was used as the standard reference. RESULTS:A total of 12845 segments were evaluated in 894 patients, among which 4955 calcified plaques were detected on 3645(28.4%) segments by CCTA. The overall AUC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.939, 97.8%, 90.1%, 71.2% and 99.4%, respectively. In type I-II calcification, CCTA had high diagnostic performance in AUC (type I: 0.983; type II: 0.976), sensitivity (96.7%; 98.1%), specificity (99.8%; 97.0%), PPV (95.7%; 90.1%), NPV (99.8%; 99.5%) and accuracy (99.6%; 97.3%). In type III-IV calcification, CCTA has high performance in sensitivity (type III: 97.6%; type IV: 97.9%) and NPV (98.3%; 98.7%), moderate performance in AUC (0.877; 0.829), while remarkable decrease in specificity (78.7%; 67.9%), PPV (71.0%; 56.2%) and accuracy (84.9%; 76.8%). CONCLUSION:CCTA has highest accuracy in diagnosing the coronary artery stenosis of type I-II calcified plaques, but has a significant decrease in specificity, PPV and accuracy in type III-IV calcified plaque.

Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion 12C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC)-Electrospray Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/μm, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/μm, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/μm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation) and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1 responded better at lower dosages than at higher dosages, implying that cell damage would occur when the networks involving these proteins stop responding. Our investigation provides valuable proteomic information for elucidating the mechanism of biological effects induced by carbon ions in general.

Epidemiological data suggest that omega-6 (ω-6) fatty acids (FAs) may be associated with cancer incidence and/or cancer mortality, whereas ω-3 FAs are potentially protective. We examined the association of the ratio of ω-6 to ω-3 FA (ω-6:ω-3) and individual FA components with pathological results among men with prostate cancer (PCa) undergoing radical prostatectomy.Sixty-nine men were included in the study. Components of ω-6 (linoleic acid (LA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA)) and ω-3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) were analyzed by liquid chromatography/mass selective detector separation. Logistic regression analysis was performed to determine association of FA with pathological high grade (Gleason ≥4+3) disease.The were 35 men with low grade disease (Gleason ≤3+4) and 34 men with high grade disease. Men with low grade disease were significantly younger (58y vs 61y, p = 0.012) and had lower D'Amico clinical classification (p = 0.001) compared to men with high grade disease. There was no significant association of ω-6:ω-3 with high grade disease (OR 0.93, p = 0.78), however overall ω-6, ω-3, and individual components of ω-6 and ω-3 FAs except EPA were significantly associated with high grade disease (ω-6: OR 3.37, 95% CI: 1.27,8.98; LA: OR 3.33, 95% CI:1.24,8.94; AA: OR 2.93, 95% CI:1.24,6.94; DGLA: OR 3.21, 95% CI:1.28,8.04; ω-3: OR 3.47, 95% CI:1.22,9.83; DHA: OR 3.13, 95% CI:1.26,7.74). ω-6 and ω-3 FA components were highly correlated (Spearman ρ = 0.77).Higher levels of individual components of ω-6 and ω-3FAs may be associated with higher-grade PCa.Studies into the causative factors/pathways regarding FAs and prostate carcinogenesis may prove a potential association with PCa aggressiveness.

In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pediatric CHD patients at five different time points: before CPB, immediately after CPB, and 1, 3, and 7 days after CPB. Real-time PCR, Western blot, and ELISA were performed to measure the expression of NOD1 and NOD2, their downstream signaling pathways, and inflammatory cytokines at various time points. Proinflammatory cytokine IL-6 and TNF-α levels in response to stimulation with either the NOD1 agonist Tri-DAP or the NOD2 agonist MDP were significantly reduced after CPB compared with those before CPB, which is consistent with a suppressed inflammatory response postoperatively. The expression of phosphorylated RIP2 and activation of the downstream signaling pathways NF-κB p65 and MAPK p38 upon Tri-DAP or MDP stimulation in PBMCs were substantially inhibited after CPB. The mRNA level of NOD1 and protein levels of NOD1 and NOD2 were also markedly decreased after CPB. Our results demonstrated that NOD-mediated signaling pathways were substantially inhibited after CPB, which correlates with the suppressed inflammatory response and may account, at least in part, for the increased risk of postoperative infection in pediatric CHD patients.

Land use change and climate variability are two key factors impacting watershed hydrology, which is strongly related to the availability of water resources and the sustainability of local ecosystems. This study assessed separate and combined hydrological impacts of land use change and climate variability in the headwater region of a typical arid inland river basin, known as the Heihe River Basin, northwest China, in the recent past (1995-2014) and near future (2015-2024), by combining two land use models (i.e., Markov chain model and Dyna-CLUE) with a hydrological model (i.e., SWAT). The potential impacts in the near future were explored using projected land use patterns and hypothetical climate scenarios established on the basis of analyzing long-term climatic observations. Land use changes in the recent past are dominated by the expansion of grassland and a decrease in farmland; meanwhile the climate develops with a wetting and warming trend. Land use changes in this period induce slight reductions in surface runoff, groundwater discharge and streamflow whereas climate changes produce pronounced increases in them. The joint hydrological impacts are similar to those solely induced by climate changes. Spatially, both the effects of land use change and climate variability vary with the sub-basin. The influences of land use changes are more identifiable in some sub-basins, compared with the basin-wide impacts. In the near future, climate changes tend to affect the hydrological regimes much more prominently than land use changes, leading to significant increases in all hydrological components. Nevertheless, the role of land use change should not be overlooked, especially if the climate becomes drier in the future, as in this case it may magnify the hydrological responses.

Attention is important in error processing. Few studies have examined the link between sustained attention and error processing. In this study, we examined how error-related negativity (ERN) of a four-choice reaction time task was reduced in the mental fatigue condition and investigated the role of sustained attention in error processing. Forty-one recruited participants were divided into two groups. In the fatigue experiment group, 20 subjects performed a fatigue experiment and an additional continuous psychomotor vigilance test (PVT) for 1 h. In the normal experiment group, 21 subjects only performed the normal experimental procedures without the PVT test. Fatigue and sustained attention states were assessed with a questionnaire. Event-related potential results showed that ERN (p < 0.005) and peak (p < 0.05) mean amplitudes decreased in the fatigue experiment. ERN amplitudes were significantly associated with the attention and fatigue states in electrodes Fz, FC1, Cz, and FC2. These findings indicated that sustained attention was related to error processing and that decreased attention is likely the cause of error processing impairment.

BACKGROUND:Colorectal cancer (CRC) is a major burden of public health and healthcare worldwide. Microbiota has been suggested in promoting chronic inflammation in the intestine which, in turn, promotes tumor development. This study focuses on possible correlations of human papillomavirus (HPV) infection with proinflammatory Stat3 signaling activities and the resulting levels of its downstream proinflammatory cytokine IL-17 in CRC patients. METHODS:HPV was examined using HPV Genotyping Chip technology and constitutively active Stat3 (p-Stat3) and IL-17 levels were tested using immunohistochemistry (IHC) in paraffin-embedded cancerous and adjacent normal tissues (ANT) from a cohort of 95 CRC patients. Correlation analyses were performed between HPV infection and clinicopathological characteristics, Stat3 activities and IL-17 levels among these CRC patients. RESULTS:Three major findings were observed: (1) HPV infection existed in a high rate of CRC cases (48.4%, 46/95), of which 45 cases (45/46, 97.8%) were high-risk HPV16-positive and only one case was HPV53-positive. (2) HPV infection correlated with poorer clinical stages (III+IV) of CRC. (3) HPV infection strongly correlated with both constitutively higher Stat3 activities (P

NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb) is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender×age×brain regions) remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender×age×brain regions), as well as the NDR1/2 kinase expression. Sprague-Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real-time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender×age×brain regions effects and related to NDR1/2 signal expression.

OBJECTIVE:Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. METHODS:Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. RESULTS:Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). CONCLUSIONS:A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.

Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P

Pseudomonas aeruginosa employs a type three secretion system to facilitate infections in mammalian hosts. The operons encoding genes of structural components of the secretion machinery and associated virulence factors are all under the control of the AraC-type transcriptional activator protein, ExsA. ExsA belongs to a unique subfamily of AraC-proteins that is regulated through protein-protein contacts rather than small molecule ligands. Prior to infection, ExsA is inhibited through a direct interaction with the anti-activator ExsD. To activate ExsA upon host cell contact this interaction is disrupted by the anti-antiactivator protein ExsC. Here we report the crystal structure of the regulatory domain of ExsA, which is known to mediate ExsA dimerization as well as ExsD binding. The crystal structure suggests two models for the ExsA dimer. Both models confirmed the previously shown involvement of helix α-3 in ExsA dimerization but one also suggest a role for helix α-2. These structural data are supported by the observation that a mutation in α-2 greatly diminished the ability of ExsA to activate transcription in vitro. Additional in vitro transcription studies revealed that a conserved pocket, used by AraC and the related ToxT protein for the binding of small molecule regulators, although present in ExsA is not involved in binding of ExsD.

Mechanisms of plant root tolerance to high temperatures through antioxidant defense are not well understood. The objective of this study was to investigate whether superior root thermotolerance of heat-tolerant Agrostis scabra relative to its congeneric heat-sensitive Agrostis stolonifera was associated with differential accumulation of reactive oxygen species and antioxidant scavenging systems. A. scabra 'NTAS' and A. stolonifera 'Penncross' plants were exposed to heat stress (35/30°C, day/night) in growth chambers for 24 d. Superoxide (O2(-)) content increased in both A. stolonifera and A. scabra roots under heat stress but to a far lesser extent in A. scabra than in A. stolonifera. Hydrogen peroxide (H2O2) content increased significantly in A. stolonifera roots but not in A. scabra roots responding to heat stress. The content of antioxidant compounds (ascorbate and glutathione) did not differ between A. stolonifera and A. scabra under heat stress. Enzymatic activity of superoxide dismutase was less suppressed in A. scabra than that in A. stolonifera under heat stress, while peroxidase and catalase were more induced in A. scabra than in A. stolonifera. Similarly, their encoded transcript levels were either less suppressed, or more induced in A. scabra roots than those in A. stolonifera during heat stress. Roots of A. scabra exhibited greater alternative respiration rate and lower cytochrome respiration rate under heat stress, which was associated with suppression of O2(-) and H2O2 production as shown by respiration inhibitors. Superior root thermotolerance of A. scabra was related to decreases in H2O2 and O2(-) accumulation facilitated by active enzymatic antioxidant defense systems and the maintenance of alternative respiration, alleviating cellular damages by heat-induced oxidative stress.

Transanal endoscopic microsurgery (TEM) for the treatment of early-stage rectal cancer has attracted attention due to its advantages of reduced surgical trauma, fewer complications, low operative mortality, rapid postoperative recovery and short hospital stay. However, there are still significant controversies regarding TEM for the treatment of rectal cancer, mainly related to the prognosis associated with this method.This study sought to compare the efficacy of transanal endoscopic microsurgery (TEM) and total mesorectal excision (TME) for the treatment of T1 rectal cancer.We searched the Cochrane Library, PubMed, Embase and CNKI databases. Based on the Cochrane Handbook for Systematic Reviews, we screened the trials, evaluated the quality and extracted the data.One randomized controlled trial (RCT) and six non-randomized controlled clinical trials (CCTs) were included in the meta-analysis (a total of 860 rectal cancer patients were included; 303 patients were treated with TEM, and 557 patients were treated with TME). Analysis revealed that all seven studies reported local recurrence rates, and there was a significant difference between the TEM and TME groups [odds ratio (OR) = 4.62, 95% confidence interval (CI) (2.03, 10.53), P = 0.0003]. A total of five studies reported distant metastasis rates, and there was no significant difference between the TEM and TME groups [OR = 0.74, 95%CI (0.32, 1.72), P = 0.49]. A total of six studies reported postoperative overall survival of the patients, and there was no significant difference between the TEM and TME groups [OR = 0.87, 95%CI(0.55, 1.38), P = 0.55]. In addition, two studies reported the postoperative disease-free survival rates of patients, and there was no significant difference between the TEM and TME groups [OR = 1.12, 95%CI (0.31, 4.12), P = 0.86].For patients with T1 rectal cancer, the distant metastasis, overall survival and disease-free survival rates did not differ between the TEM and TME groups, although the local recurrence rate after TEM was higher than that after TME.

Members of the genera Prevotella, Veillonella and Fusobacterium are the predominant culturable obligate anaerobic bacteria isolated from periodontal abscesses. When determining the cumulative number of clinical anaerobic isolates from periodontal abscesses, ambiguous or overlapping signals were frequently encountered in 16S rRNA gene sequencing chromatograms, resulting in ambiguous identifications. With the exception of the genus Veillonella, the high intra-chromosomal heterogeneity of rrs genes has not been reported.The 16S rRNA genes of 138 clinical, strictly anaerobic isolates and one reference strain were directly sequenced, and the chromatograms were carefully examined. Gene cloning was performed for 22 typical isolates with doublet sequencing signals for the 16S rRNA genes, and four copies of the rrs-ITS genes of 9 Prevotella intermedia isolates were separately amplified by PCR, sequenced and compared. Five conserved housekeeping genes, hsp60, recA, dnaJ, gyrB1 and rpoB from 89 clinical isolates of Prevotella were also amplified by PCR and sequenced for identification and phylogenetic analysis along with 18 Prevotella reference strains.Heterogeneity of 16S rRNA genes was apparent in clinical, strictly anaerobic oral bacteria, particularly in the genera Prevotella and Veillonella. One hundred out of 138 anaerobic strains (72%) had intragenomic nucleotide polymorphisms (SNPs) in multiple locations, and 13 strains (9.4%) had intragenomic insertions or deletions in the 16S rRNA gene. In the genera Prevotella and Veillonella, 75% (67/89) and 100% (19/19) of the strains had SNPs in the 16S rRNA gene, respectively. Gene cloning and separate amplifications of four copies of the rrs-ITS genes confirmed that 2 to 4 heterogeneous 16S rRNA copies existed.Sequence alignment of five housekeeping genes revealed that intra-species nucleotide similarities were very high in the genera Prevotella, ranging from 94.3-100%. However, the inter-species similarities were relatively low, ranging from 68.7-97.9%. The housekeeping genes rpoB and gyrB1 were demonstrated to be alternative classification markers to the species level based on intra- and inter-species comparisons, whereas based on phylogenetic tree rpoB proved to be reliable phylogenetic marker for the genus Prevotella.

The increasing prevalence and mortality of multidrug-resistant (MDR) Acinetobacter baumannii complex-associated infections, especially bacteremia, in health care settings poses a great threat to public health. We proceeded to investigate the risk and prognostic factors for MDR A. baumannii complex bacteremia in mainland China.This retrospective study was conducted at West China Hospital from January 2009 to December 2013. Using a computer-assisted microbiology laboratory database, patients with MDR A. baumannii complex bacteremia were included as the case group, while those infected with non-MDR A. baumannii complex were selected as the control group. The clinical data were collected and analyzed.There were 241 non-duplicated A. baumannii complex blood isolates identified in our research, with the overall rate of multidrug resistance reaching 75.52% over the past five years. Using multivariate logistic analysis, being in the intensive care unit (ICU) (adjusted odds ratio [aOR], 5.84; 95% confidence interval [CI], 1.67-20.44), increased Pittsburgh bacteremia score (aOR, 6.55; 95% CI, 1.27-33.70) and use of carbapenem (aOR, 8.90; 95% CI, 1.71-46.30) were independent risk factors for MDR acquisition among patients with A. baumannii complex bacteremia. Older age (aOR, 1.02; 95% CI, 1.00-1.04), being post-transplantation (aOR, 5.21; 95% CI, 1.13-24.04), having a higher Pittsburgh bacteremia score (aOR, 2.19; 95% CI, 1.08-4.47) and having a lower level of albumin (aOR, 0.93; 95% CI, 0.88-0.99) were identified as independent risk factors for 30-day mortality in patients with MDR A. baumannii complex bacteremia.In conclusion, our research revealed the risk factors associated with acquisition of and mortality from MDR A. baumannii complex bacteremia, which may be used to prioritize infection control practices and prognostic evaluations.

In this paper, an entropy-based method is proposed to forecast the demographical changes of countries. We formulate the estimation of future demographical profiles as a constrained optimization problem, anchored on the empirically validated assumption that the entropy of age distribution is increasing in time. The procedure of the proposed method involves three stages, namely: 1) Prediction of the age distribution of a country's population based on an "age-structured population model"; 2) Estimation the age distribution of each individual household size with an entropy-based formulation based on an "individual household size model"; and 3) Estimation the number of each household size based on a "total household size model". The last stage is achieved by projecting the age distribution of the country's population (obtained in stage 1) onto the age distributions of individual household sizes (obtained in stage 2). The effectiveness of the proposed method is demonstrated by feeding real world data, and it is general and versatile enough to be extended to other time dependent demographic variables.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.In situ hybridization (ISH) analysis of Epstein-Barr virus (EBV) and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3) was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.A total of 16 patients (7.0%) were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB) subtypes (87.5%) and high Ki67 (75%) and CD30 expression (93.8%). For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8%) had complete remission, 2 (12.5%) had partial remission, 2 (12.5%) had stable disease, and 5 (31.3%) had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P

Forest health issues are on the rise in the United States, resulting from introduction of alien pests and diseases, coupled with abiotic stresses related to climate change. Increasingly, forest scientists are finding genetic/genomic resources valuable in addressing forest health issues. For a set of ten ecologically and economically important native hardwood tree species representing a broad phylogenetic spectrum, we used low coverage whole genome sequencing from multiplex Illumina paired ends to economically profile their genomic content. For six species, the genome content was further analyzed by flow cytometry in order to determine the nuclear genome size. Sequencing yielded a depth of 0.8X to 7.5X, from which in silico analysis yielded preliminary estimates of gene and repetitive sequence content in the genome for each species. Thousands of genomic SSRs were identified, with a clear predisposition toward dinucleotide repeats and AT-rich repeat motifs. Flanking primers were designed for SSR loci for all ten species, ranging from 891 loci in sugar maple to 18,167 in redbay. In summary, we have demonstrated that useful preliminary genome information including repeat content, gene content and useful SSR markers can be obtained at low cost and time input from a single lane of Illumina multiplex sequence.

To study the main molecular mechanisms responsible for itraconazole resistance in clinical isolates of Candida krusei.The 14α-demethylases encoded by ERG11 gene in the 16 C.krusei clinical isolates were amplified by polymerase chain reaction (PCR), and their nucleotide sequences were determined to detect point mutations. Meanwhile, ERG11 and efflux transporters (ABC1 and ABC2) genes were determined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) for their expression in itraconazole-resistant (R), itraconazole-susceptible dose dependent (SDD) and itraconazole-susceptible (S) C.krusei at the mRNA level.We found 7-point mutations in ERG11 gene of all the C.krusei clinical isolates, including 6 synonymous mutations and 1 missense mutation (C44T). However, the missense mutation was found in the three groups. The mRNA levels of ERG11 gene in itraconazole-resistant isolates showed higher expression compared with itraconazole-susceptible dose dependent and itraconazole-susceptible ones (P = 0.015 and P = 0.002 respectively). ABC2 gene mRNA levels in itraconazole-resistant group was significantly higher than the other two groups, and the levels of their expression in the isolates appeared to increase with the decrease of susceptibility to itraconazole (P = 0.007 in SDD compared with S, P = 0.016 in SDD with R, and P

ObjectiveSoluble fms-like tyrosine kinase (sFlt)-1-e15a, a primate-specific sFlt-1-isoform most abundant in the human placenta in preeclampsia, can induce preeclampsia in mice. This study compared the effects of full-length human (h)sFlt-1-e15a with those of truncated mouse (m)sFlt-1(1-3) used in previous preeclampsia studies on pregnancy outcome and clinical symptoms in preeclampsia.MethodsMice were injected with adenoviruses or fiber-mutant adenoviruses overexpressing hsFlt-1-e15a, msFlt-1(1-3) or control GFP under the CMV or CYP19A1 promoters on gestational day 8 (GD8) and GD11. Placentas and pups were delivered by cesarean section, and dams were monitored postpartum. Blood pressure was telemetrically recorded. Urine samples were collected with cystocentesis and examined for albumin/creatinine ratios. Tissue specimens were evaluated for transgene as well as endogenous mFlt-1 and msFlt-1-i13 expression. H&E-, Jones- and PAS-stained kidney sections were histopathologically examined. Placental GFP expression and aortic ring assays were investigated with confocal microscopy.ResultsMean arterial blood pressure (MAP) was elevated before delivery in hsFlt-1-e15a-treated mice compared to controls (GD18: ΔMAP = 7.8 mmHg, p = 0.009), while ΔMAP was 12.8 mmHg (GD18, p = 0.005) in msFlt-1(1-3)-treated mice. Urine albumin/creatinine ratio was higher in hsFlt-1-e15a-treated mice than in controls (GD18, p = 0.04; PPD8, p = 0.03), and msFlt-1(1-3)-treated mice had marked proteinuria postpartum (PPD8, p = 4 × 10(-5)). Focal glomerular changes were detected in hsFlt-1-e15a and msFlt-1(1-3)-treated mice. Aortic ring microvessel outgrowth was decreased in hsFlt-1-e15a (p = 0.007) and msFlt-1(1-3)-treated (p = 0.02) mice. Full-length msFlt-1-i13 expression was unique for the placenta. In hsFlt-1-e15a-treated mice, the number of pups (p = 0.046), total weight of living pups (p = 0.04) and maternal weights (p = 0.04) were higher than in controls. These differences were not observed in truncated msFlt-1(1-3)-treated mice.ConclusionsTruncated msFlt-1(1-3) simulated the preeclampsia-promoting effects of full-length hsFlt-1. MsFlt-1(1-3) had strong effect on maternal endothelium but not on placentas and embryos. In contrast, hsFlt-1-e15a induced preeclampsia-like symptoms; however, it also increased litter size. In accord with the predominant placental expression of hsFlt-1-e15a and msFlt-1-i13, full-length sFlt-1 may have a role in the regulation of embryonic development. These observations point to the difference in the biological effects of full-length and truncated sFlt-1 and the changes in the effect of full-length sFlt-1 during pregnancy, and may have important implications in the management of preeclampsia.