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BackgroundTraditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear.MethodsIn this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis.ResultsNetwork pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway.ConclusionWe conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.

At present, there are some problems in underwater low light image, such as low contrast, blurred details, color distortion. In the process of low illumination image enhancement, there are often problems such as artifacts, loss of edge details and noise amplification in the enhanced image. In this paper, we propose an underwater low-light enhancement algorithm based on U-shaped generative adversarial network, combined with bright channel prior and attention mechanism, to address the problems. For the problems of uneven edges and loss of details that occurred in traditional enhanced images, we propose a two-channel fusion technique for the input channel. Aiming at the problems of brightness, texture and color distortion in enhanced images, we propose a feature extraction technique based on the attention mechanism. For the problems of noise in enhanced output images, we propose a multi-loss function to constrain the network. The method has a wide range of applications in underwater scenes with large depth. This method can be used for target detection or biological species identification in underwater low light environment. Through the enhancement experiment of underwater low light image, the proposed method effectively solves the problems of low contrast, blurred details, color distortion, etc. of underwater low light image. Finally, we performed extensive comparison experiments and completed ablation experiments on the proposed method. The experimental results show that the proposed method is optimal in human visual experience and underwater image quality evaluation index.

Tissue slicing-assisted digestion (TSAD) of adult cardiomyocytes has shown significant improvements over conventional chunk methods. However, it remains unclear how this method compares to Langendorff perfusion, the current standard of adult cardiomyocyte isolation. Using adult Bama minipigs, we performed cardiomyocyte isolation via these two distinct methods, and compared the resulting cellular quality, including viability, cellular structure, gene expression, and electrophysiological properties, of cardiomyocytes from 3 distinct anatomical regions, namely the left ventricle, right ventricle, and left atrial appendage. Our results revealed largely indistinguishable cell quality in all of the measured parameters. These findings suggest that that TSAD can be reliably used to isolate adult mammalian cardiomyocytes as a reliable alternative to perfusion in cardiomyocyte isolation from larger mammals, particularly when Langendorff perfusion is not feasible.

FOXP1, known as a Forkhead-box (FOX) family protein, plays an important role in human tumorigenesis. However, the function and molecular mechanism of FOXP1 in pancreatic cancer (PC) remain unclear. Here, we report that PC patients with FOXP1 overexpression had a higher survival rate compared to patients with low- FOXP1 expression. Additionally, high expression of FOXP1 can markedly inhibit the growth of pancreatic cancer in vivo and in vitro, whereas low expression of FOXP1 effectively promoted the tumorigenesis. Mechanistically, FOXP1 could directly bind the IRF1 promoter, which triggered the transcriptional activity of IRF1. Taken together, FOXP1 suppressed PC growth via IRF1-dependent manner, serving as a potential prognostic biomarker for patients with PC.

During the production of electronic panels, surface defects will inevitably appear. How to quickly and accurately detect these defects is very important to improve product quality. However, some problems such as high cost and low accuracy are still prominent when existing manual detection and traditional techniques are used to solve such problems. Therefore, more and more computer vision techniques are proposed to solve such problems, but the current application of deep learning-based object detection networks for surface defect detection of electronic panels is in a gap. The analysis found that there are two main reasons for this phenomenon. On the one hand, the surface defects of electronic panels have their unique characteristics such as multi-scale and irregular shape, and the current object detection networks cannot effectively solve these problems. On the other hand, the regression and classification tasks coupled in the current computational mechanism of each network are commonly found to cause the problem of conflict between them, which makes it more difficult to adapt these network models to the detection tasks in this scenario. Based on this, we design a supervised object detection network for electronic panel surface defect detection scenario for the first time. The computational mechanism of this network includes a prediction box generation strategy based on the double branch structure and a detection head design strategy that decouples the regression task from the classification task. In addition, we validated the designed network and the proposed method on our own collected dataset of surface defects in electronic panels. The final results of the comparative and ablation experiments show that our proposed method achieves an average accuracy of 78.897% for 64 surface defect categories, proving that its application to electronic panel surface defect detection scenarios can achieve better results.

Automatic detection of surface defects in electronic panels is receiving increasing attention in the quality control of products. The surface defect detection of electronic panels is different from other target detection scenarios and is a meaningful and challenging problem. Its main manifestation is that surface defects of electronic panels usually exhibit extreme irregularity and small target characteristics, which bring great difficulties to the task of surface defect target detection including feature extraction and so on. The traditional methods can only detect a very small number of defect classes under specific detection conditions. And due to the weak robustness of these methods, they cannot be applied in real production scenarios on a large scale. Based on this, this paper applies the target detection technique under deep learning to the surface defect detection scenario of electronic panels for the first time. At the same time, in order to make the designed target detection network applicable to the electronic panel surface defect detection scenario and to enhance the interpretability of the designed target detection network in terms of computer mechanism. We design a deformable convolution module with a convolutional self-attentive module to learn the offset and a dual detection head incorporating the SE (Squeeze-and-Excitation) mechanism for the irregular characteristics of electronic panel surface defects and the small target characteristics, respectively. Finally, we carried out a series of experiments on our own electronic panel defect data set, including comparison with the most advanced target detection algorithms and a series of ablation experiments against our proposed method. The final experimental results prove that our method not only has better interpretability, but also has better metric performance, in which the map_0.5 metric reaches 78.257%, which is an increase of 13.506 percentage points over YOLOV5 and 33.457 percentage points higher than Retinanet. The results prove the proposed method is effective.

In recent years, high utility itemsets (HUIs) mining has been an active research topic in data mining. In this study, we propose two efficient pattern-growth based HUI mining algorithms, called High Utility Itemset based on Length and Tail-Node tree (HUIL-TN) and High Utility Itemset based on Tail-Node tree (HUI-TN). These two algorithms avoid the time-consuming candidate generation stage and the need of scanning the original dataset multiple times for exact utility values. A novel tree structure, named tail-node tree (TN-tree) is proposed as a key element of our algorithms to maintain complete utililty-information of existing itemsets of a dataset. The performance of HUIL-TN and HUI-TN was evaluated against state-of-the-art reference methods on various datasets. Experimental results showed that our algorithms exceed or close to the best performance on all datasets in terms of running time, while other algorithms can only excel in certain types of dataset. Scalability tests were also performed and our algorithms obtained the flattest curves among all competitors.

In water scenes, where hazy images are subject to multiple scattering and where ideal data sets are difficult to collect, many dehazing methods are not as effective as they could be. Therefore, an unsupervised water scene dehazing network using atmospheric multiple scattering model is proposed. Unlike previous image dehazing methods, our method uses the unsupervised neural network and the atmospheric multiple scattering model and solves the problem of difficult acquisition of ideal datasets and the effect of multiple scattering on the image. In our method, in order to embed the atmospheric multiple scattering model into the unsupervised dehazing network, the unsupervised dehazing network uses four branches to estimate the scene radiation layer, transmission map layer, blur kernel layer and atmospheric light layer, the hazy image is then synthesized from the four output layers, minimizing the input hazy image and the output hazy image, where the output scene radiation layer is the final dehazing image. In addition, we constructed unsupervised loss functions which applicable to image dehazing by prior knowledge, i.e., color attenuation energy loss and dark channel loss. The method has a wide range of applications, with haze being thick and variable in marine, river and lake scenes, the method can be used to assist ship vision for target detection or forward road recognition in hazy conditions. Through extensive experiments on synthetic and real-world images, the proposed method is able to recover the details, structure and texture of the water image better than five advanced dehazing methods.

BACKGROUND:The expression of the L-type amino acid transporter 1 (LAT1) plays a significant role in tumor progression. However, it remains unclear whether high LAT1 expression correlates with poor prognosis of solid tumor patients. Here, we conducted a meta-analysis to assess the potential of LAT1 in predicting the prognosis of tumor patients. METHODS AND FINDINGS:A total of 4,579 cases were analyzed from 35 qualified studies. In patients with solid tumors, elevated expression of LAT1 is associated with poor prognosis (overall survival [OS]: pooled hazard ratio (HR) = 1.848, 95% confidence interval (CI) = 1.620-2.108, P < 0.001; disease free survival [DFS]: pooled HR = 1.923, 95% CI = 1.585-2.333, P < 0.001; progression free survival [PFS]: pooled HR = 1.345, 95% CI = 1.133-1.597, P = 0.001). Furthermore, in subgroup analysis, we found an association between high LAT1 expression and poor OS in non-small cell lung cancer (HR = 1.554, 95% CI = 1.345-1.794, P < 0.001), pancreatic cancer (HR = 2.052, 95% CI = 1.613-2.724, P < 0.001) and biliary tract cancer (HR = 2.253, 95% CI = 1.562-3.227, P < 0.001). CONCLUSION:The results of this meta-analysis indicate the reliability and potential of using LAT1 expression as a predictive biomarker in solid cancers prior to treatment. However, further studies with larger sample sizes would be beneficial for fully evaluating the predictive value of LAT1 expression for clinical applications.

The rice white tip nematode, Aphelenchoides besseyi, is widely distributed in rice planting areas worldwide and causes serious economic losses. Cathepsin genes have been demonstrated to have importance in studying the reproduction, development, pathogenicity, and control methods of plant nematodes. In this paper, a novel cathepsin B gene, Ab-cb-1, was found and cloned. The Ab-cb-1 gene was 1347 bp in length and encodes 369 amino acids. The Ab-CB-1 protein contains characteristic occluding loops but no signal peptide. A homology analysis showed that Ab-CB-1 had the highest identity value (64%) to the known amino acid sequence of cathepsin B-like cysteine protease 6 from Toxocara canis. When Ab-cb-1 was expressed in a prokaryotic system, the protein massed approximately 45 kDa and could decompose carrot callus. Ab-cb-1 mRNA was localized in the nematode intestine. The relative expression level of Ab-cb-1 in the A. besseyi Ab-S24 population, which had high reproductivity, was approximately 6.9 times that in the Ab-N10 population, which had low reproductivity, and the difference was significant (p

The clinical outcomes and therapeutic strategies for infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) are not uniform. The primary objectives of this study were to identify the differences in the clinical characteristics and prognoses between ILC and IDC, and identify the high-risk population based on the hormone receptor status and metastasis sites. The Surveillance, Epidemiology, and End Results Program database was searched and patients diagnosed with ILC or IDC from 1990 to 2013 were identified. In total,796,335 patients were analyzed, including 85,048 withILC (10.7%) and 711,287 withIDC (89.3%). The ILC group was correlatedwith older age, larger tumor size, later stage, lower grade, metastasis disease(M1) disease, and greater counts ofpositive lymph nodesandestrogen-receptor-positive (ER)/progesterone receptor-positive (PR) positive nodes. The overall survival showed an early advantage for ILC but a worse outcome after 5 years. Regarding the disease-specific survival, the IDC cohort had advantages over the ILC group, both during the early years and long-term. In hormone status and metastasis site subgroup analyses, the ER+/PR+ subgroup had the best survival, while the ER+/PR- subgroup had the worst outcome, especially the ILC cohort. ILC and IDC had different metastasis patterns. The proportion of bone metastasis was higher in the ILC group (91.52%) than that in the IDC (76.04%), and the ILC group was more likely to have multiple metastasis sites. Survival analyses showed patients with ILC had a higher risk of liver metastasis (disease-specific survival[DSS]; P = 0.046), but had a better overall survival than the bone metastasis group (P

Analyses of imperfectly assessed time to event outcomes give rise to biased hazard ratio estimates. This bias is a common challenge for studies of Alzheimer's Disease (AD) because AD neuropathology can only be identified through brain autopsy and is therefore not available for most study participants. Clinical AD diagnosis, although more widely available, has imperfect sensitivity and specificity relative to AD neuropathology. In this study we present a sensitivity analysis approach using a bias-adjusted discrete proportional hazards model to quantify robustness of results to misclassification of a time to event outcome and apply this method to data from a longitudinal panel study of AD. Using data on 1,955 participants from the Adult Changes in Thought study we analyzed the association between average glucose level and AD neuropathology and conducted sensitivity analyses to explore how estimated hazard ratios varied according to AD classification accuracy. Unadjusted hazard ratios were closer to the null than estimates obtained under most scenarios for misclassification investigated. Confidence interval estimates from the unadjusted model were substantially underestimated compared to adjusted estimates. This study demonstrates the importance of exploring outcome misclassification in time to event analyses and provides an approach that can be undertaken without requiring validation data.

Tea plants [Camellia sinensis (L.) O. Kuntze] are an important leaf-type crop that are widely used for the production of non-alcoholic beverages in the world. Exposure to excessive amounts of heavy metals adversely affects the quality and yield of tea leaves. To analyze the molecular responses of tea plants to heavy metals, a reliable quantification of gene expression is important and of major importance herein is the normalization of the measured expression levels for the target genes. Ideally, stably expressed reference genes should be evaluated in all experimental systems. In this study, 12 candidate reference genes (i.e., 18S rRNA, Actin, CYP, EF-1α, eIF-4α, GAPDH, MON1, PP2AA3, TBP, TIP41, TUA, and UBC) were cloned from tea plants, and the stability of their expression was examined systematically in 60 samples exposed to diverse heavy metals (i.e., manganese, aluminum, copper, iron, and zinc). Three Excel-based algorithms (geNorm, NormFinder, and BestKeeper) were used to evaluate the expression stability of these genes. PP2AA3 and 18S rRNA were the most stably expressed genes, even though their expression profiles exhibited some variability. Moreover, commonly used reference genes (i.e., GAPDH and TBP) were the least appropriate reference genes for most samples. To further validate the suitability of the analyzed reference genes, the expression level of a phytochelatin synthase gene (i.e., CsPCS1) was determined using the putative reference genes for data normalizations. Our results may be beneficial for future studies involving the quantification of relative gene expression levels in tea plants.

Recent data suggest that noninvasive liver fibrosis indexes could be useful for predicting esophageal varices (EV) in cirrhotic patients. However, thus far, the diagnostic efficacy of these indexes in predicting portal hypertension (PH) in cirrhotic patients has been poorly evaluated.To evaluate the diagnostic efficacy of noninvasive liver fibrosis indexes in the diagnosis of PH.A total of 238 cirrhotic patients underwent hepatic venous pressure gradient (HVPG) evaluation and relevant serum tests to analyze the variables associated with PH grade. Then, the diagnostic performances of seven fibrosis indexes, the aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet (PLT) ratio index (APRI), fibrosis index (FI), FIB-4, Forns index, King's score and the Lok index, were evaluated to determine their efficacy in predicting clinically significant PH (CSPH) and severe PH (SPH). In addition, the performances of these fibrosis indexes in different subgroups were investigated.The results of a multivariate analysis of serum markers showed that AST values, platelet (PLT) count and albumin (ALB) were associated with PH grade. Among the seven-fibrosis indexes, King's score, APRI and the Lok index showed modest diagnostic accuracy in predicting CSPH and SPH, as indicated by AUC of 0.755 and 0.742, 0.740 and 0.742, and 0.722 and 0.717, respectively. In addition, combination of King's score (cutoff 23.47) and Lok index (cutoff 1.30) predicted presence of CSPH, with the highest PPV (95.38%) and +LR (5.49). A subgroup analysis indicated that the noninvasive screening model may be more applicable to patients with cirrhosis of viral etiology.Serum liver fibrosis indexes exhibited modest diagnostic accuracy for PH in cirrhotic patients. These indexes may not be able to replace HVPG measurements for the diagnosis of PH but may be used as a first-line screening method for CSPH in liver cirrhosis patients.

The GeXP-based assay has recently been developed for simultaneous detection of multiple pathogens. So far, the application of the GeXP assay to test larger clinical samples has hardly been reported. Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. Rapid and accurate diagnosis of virus infection is important for the clinical management of CAP. In this study, we explored the GeXP assay for simultaneous detection of 20 types/subtypes of viruses in hospitalized children with CAP. A total of 1699 nasopharyngeal swabs were prospectively collected and viral nucleic acid was extracted and assayed. Using viral genomic DNA or RNA as template, we showed that at the concentration of 104 copies of DNA or RNA of each virus/μl, all 20 target viruses were simultaneously identified by the GeXP assay. Fifteen control microorganisms, in contrast, failed to be amplified by the assay. About 65% of cases tested in this study had viral infection, with patients aged 3 years (40%). The most frequently detected virus was RSV followed by PIV3, HRV, ADV and HBoV. Seasonal distribution analysis revealed that RSV was the most predominant in autumn and winter, while in spring and summer PIV3 and RSV were the most frequently identified with similar positive percentages. One hundred twenty randomly-chosen samples tested by the GeXP assay were re-evaluated by mono-RT-PCR, the results showed 97.5% diagnosis agreement between these 2 methods. Our findings suggest that the GeXP assay could be a valuable diagnostic tool for virus infection in pediatric patients with CAP.

Liver stiffness (LS) and spleen stiffness (SS) are two most widely accessible non-invasive parameters for predicting esophageal varices (EV), but the reported accuracy of the two predictors have been inconsistent across studies. This meta-analysis aims to evaluate the diagnostic performance of LS and SS measurement for detecting EV in patients with chronic liver disease (CLD), and compare their accuracy.Pubmed/Medline, Embase, Cochrane Library and Ovid were searched for all studies assessing SS and LS simultaneously in EV diagnosis. A total of 16 studies including 1892 patients were included in this meta-analysis, and the pooled statistical parameters were calculated using the bivariate mixed effects models.In detection of any EV, for LS measurement, the summary sensitivity was 0.83 (95% confidence interval [CI]: 0.78-0.87), and the specificity was 0.66 (95% CI: 0.60-0.72). While for SS measurement, the pooled sensitivity and specificity was 0.88 (95% CI: 0.83-0.92) and 0.78 (95% CI: 0.73-0.83). The summary receiver operating characteristic (SROC) curve values of LS and SS were 0.81 (95% CI: 0.77-0.84) and 0.88 (95% CI: 0.85-0.91) respectively, and the results had statistical significance (P

Respiratory viruses are among the most important causes of human morbidity and mortality worldwide, especially for infants and young children. In the past years, a few commercial multiplex RT-PCR assays have been used to detect respiratory viruses in spite of the high cost. In the present study, an improved single-tube multiplex reverse transcription PCR assay for simultaneous detection of 13 respiratory viruses was evaluated and compared with a previously reported two-tube assay as the reference method using clinical nasopharyngeal aspirates samples. Of 310 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 226 (72.90%, 226/310) and 214 (69.03%, 214/310) positive for one or more viruses were identified by the single-tube and the two-tube assays, respectively, with combined test results showing good concordance (Kappa value = 0.874). Individually, the single-tube assay for adenovirus (Adv), human metapneumovirus (HMPV), human rhinovirus (HRV), parainfluenza virus type 1 (PIV1), parainfluenza virus type 3 (PIV3) and parainfluenza virus type 4 (PIV4) showed the significantly superior sensitivities to those of the two-tube assay. No false positives were found. In conclusion, our results demonstrates the one-tube assay revealed significant improvements over the two-tube assay in terms of the better sensitivity, more accurate quality control, less nonspecific amplification, more cost-effective and shorter turn-around time and will be a valuable tool for routine surveillance of respiratory virus infection in China.

Vaginal swabs taken in rape cases usually contain epithelial cells from the victim and sperm from the assailant and forensic DNA analysis requires separation of sperm from these cell mixtures. PH-20, which is a glycosylphosphatidylinositol-anchored hyaluronidase located on the head of sperm, has important functions in fertilization. Here we describe a newly developed method for sperm isolation using anti-PH-20 antibody-coupled immunomagnetic beads (anti-PH-20 IMBs). Optical microscopy and scanning electron microscopy showed the IMBs recognized the head of sperm specifically and exhibited a great capacity to capture sperm cells. However, we found it necessary to incubate the IMB-sperm complex with DNase I before sperm lysis in order to remove any female DNA completely. We compared the sensitivity of anti-PH-20 IMBs in sperm and epithelial cell discrimination to those coated with a different anti-sperm antibody (anti-SP-10, anti-ADAM2 or anti-JLP). Only the anti-PH-20 IMBs succeeded in isolating sperm from cell mixtures at a sperm/epithelial cell ratio of 103:105. Further, our method exhibited greater power and better stability for sperm isolation compared to the traditional differential lysis strategy. Taken together, the anti-PH-20 IMB method described here could be effective for the isolation of sperm needed to obtain a single-sourced DNA profile as an aid to identifying the perpetrator in sexual assault cases.

Residual renal function (RRF) is an important prognostic factor for peritoneal dialysis patients as it influences the quality of life and mortality. This study was conducted to explore the potential factors correlated with RRF. A cross-sectional study was conducted by recruiting 155 patients with residual GFR more than 1mL/min per 1.73m2 at the initiation of peritoneal dialysis. We collected the demographic characteristics, nutritional markers and biochemical parameters of all participants, and analyzed the correlation between these variables and residual GFR as well. The odds ratio of RRF loss associated with each of the nutritional markers and biochemical parameters were estimated by logistic regression model. The residual GFR was negatively correlated with serum phosphate (ORQ3 = 2.67, 95%CI: 1.03-6.92; ORQ4 = 3.45, 95%CI: 1.35-9.04), magnesium (ORQ4 = 3.77, 95%CI: 1.48-3.63), and creatinine (ORQ3 = 2.93, 95%CI: 1.09-7.88; ORQ4 = 8.64 95%CI: 2.79-26.78), while positively associated with normalized protein catabolic rate (ORQ3 = 0.24, 95%CI: 0.09-0.65; ORQ4 = 0.11, 95%CI: 0.03-0.35), 24 hours urine volume(ORQ1 = 22.87, 95%CI: 2.76-189.24; ORQ3 = 0.08, 95%CI: 0.02-0.28) and serum chlorine concentrations (ORQ1 = 5.34, 95%CI: 1.94-14.68; ORQ4 = 0.28, 95%CI: 0.09-0.85), respectively. Our study suggested that the nutritional markers and biochemical parameters, though not all, but at least in part were closely correlated with RRF in peritoneal dialysis patients.

The common coral trout is one species of major importance in commercial fisheries and aquaculture. Recently, two different color morphs of Plectropomus leopardus were discovered and the biological importance of the color difference is unknown. Since coral trout species are poorly characterized at the molecular level, we undertook the transcriptomic characterization of the two color morphs, one black and one red coral trout, using Illumina next generation sequencing technologies. The study produced 55162966 and 54588952 paired-end reads, for black and red trout, respectively. De novo transcriptome assembly generated 95367 and 99424 unique sequences in black and red trout, respectively, with 88813 sequences shared between them. Approximately 50% of both trancriptomes were functionally annotated by BLAST searches against protein databases. The two trancriptomes were enriched into 25 functional categories and showed similar profiles of Gene Ontology category compositions. 34110 unigenes were grouped into 259 KEGG pathways. Moreover, we identified 14649 simple sequence repeats (SSRs) and designed primers for potential application. We also discovered 130524 putative single nucleotide polymorphisms (SNPs) in the two transcriptomes, supplying potential genomic resources for the coral trout species. In addition, we identified 936 fast-evolving genes and 165 candidate genes under positive selection between the two color morphs. Finally, 38 candidate genes underlying the mechanism of color and pigmentation were also isolated. This study presents the first transcriptome resources for the common coral trout and provides basic information for the development of genomic tools for the identification, conservation, and understanding of the speciation and local adaptation of coral reef fish species.

Salinity is a major limiting factor for agricultural production worldwide. A better understanding of the mechanisms of salinity stress response will aid efforts to improve plant salt tolerance. In this study, a combination of small RNA and mRNA degradome sequencing was used to identify salinity responsive-miRNAs and their targets in barley. A total of 152 miRNAs belonging to 126 families were identified, of which 44 were found to be salinity responsive with 30 up-regulated and 25 down-regulated respectively. The majority of the salinity-responsive miRNAs were up-regulated at the 8h time point, while down-regulated at the 3h and 27h time points. The targets of these miRNAs were further detected by degradome sequencing coupled with bioinformatics prediction. Finally, qRT-PCR was used to validate the identified miRNA and their targets. Our study systematically investigated the expression profile of miRNA and their targets in barley during salinity stress phase, which can contribute to understanding how miRNAs respond to salinity stress in barley and other cereal crops.

Fgf21 is a newly discovered fibroblast growth factor. It is typically induced by fasting and plays important roles in the regulation of glucose and lipid metabolisms and energy balance in mammals, whereas potential functions of this gene in teleosts are still unknown. We identified the Fgf21 gene and studied its functions in Asian seabass (Lates calcarifer). The cDNA of the Fgf21 encoded a protein with 206 amino acids. Analysis of DNA and amino acid sequences of Fgf21 genes revealed that the sequences and structure of the Fgf21 genes were highly conserved in vertebrates. Real-time PCR revealed that Fgf21 was exclusively expressed in the intestine and kidney, which was different from the expression profiles of mammals. Fgf21 was down-regulated under fasting, whereas it was significantly increased during the LPS challenge. Exogenous recombinant FGF21 significantly suppressed the appetite of Asian seabass. Our data suggest that Fgf21 plays a role in energy regulation and acute phase response in Asian seabass, and may have different functions in fish and mammals. In addition, we identified one SNP in Fgf21. By using this SNP, the gene was mapped on the linkage group 23, where a suggestive QTL for growth was mapped previously. Association mapping identified significant associations between Fgf21 genotypes at the SNP and growth traits. These results not only provide important information of the functions of Fgf21, but also suggest that the SNP in this gene can be used as a marker in selecting fast-growing individuals of Asian seabass.

BACKGROUND: Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention. METHODS: We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment. RESULTS: Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34-0.49; P

The genetic differentiation of many marine fish species is low. Yet local adaptation may be common in marine fish species as the vast and changing marine environment provides more chances for natural selection. Here, we used anonymous as well as known protein gene linked microsatellites and mitochondrial DNA to detect the population structure of the small yellow croaker (Larimichthys polyactis) in the Northwest Pacific marginal seas. Among these loci, we detected at least two microsatellites, anonymous H16 and HSP27 to be clearly under diversifying selection in outlier tests. Sequence cloning and analysis revealed that H16 was located in the intron of BAHCC1 gene. Landscape genetic analysis showed that H16 mutations were significantly associated with temperature, which further supported the diversifying selection at this locus. These marker types presented different patterns of population structure: (i) mitochondrial DNA phylogeny showed no evidence of genetic divergence and demonstrated only one glacial linage; (ii) population differentiation using putatively neutral microsatellites presented a pattern of high gene flow in the L. polyactis. In addition, several genetic barriers were identified; (iii) the population differentiation pattern revealed by loci under diversifying selection was rather different from that revealed by putatively neutral loci. The results above suggest local adaptation in the small yellow croaker. In summary, population genetic studies based on different marker types disentangle the effects of demographic history, migration, genetic drift and local adaptation on population structure and also provide valuable new insights for the design of management strategies in L. polyactis.

The digital laminae is a two layer tissue that attaches the distal phalanx to the inner hoof wall, thus suspending the horse's axial skeleton in the hoof capsule. This tissue fails at the epidermal:dermal junction in laminitic horses, causing crippling disease. Basal epithelial cells line the laminar epidermal:dermal junction, undergo physiological change in laminitic horses, and lose versican gene expression. Versican gene expression is purportedly under control of the canonical Wnt signaling pathway and is a trigger for mesenchymal-to-epithelial transition; thus, its repression in laminar epithelial cells of laminitic horses may be associated with suppression of the canonical Wnt signaling pathway and loss of the epithelial cell phenotype. In support of the former contention, we show, using laminae from healthy horses and horses with carbohydrate overload-induced laminitis, quantitative real-time polymerase chain reaction, Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis, and immunofluorescent tissue staining, that positive and negative regulatory components of the canonical Wnt signaling pathway are expressed in laminar basal epithelial cells of healthy horses. Furthermore, expression of positive regulators is suppressed and negative regulators elevated in laminae of laminitic compared to healthy horses. We also show that versican gene expression in the epithelial cells correlates positively with that of β-catenin and T-cell Factor 4, consistent with regulation by the canonical Wnt signaling pathway. In addition, gene and protein expression of β-catenin correlates positively with that of integrin β4 and both are strongly suppressed in laminar basal epithelial cells of laminitic horses, which remain E-cadherin(+)/vimentin(-), excluding mesenchymal transition as contributing to loss of the adherens junction and hemidesmosome components. We propose that suppression of the canonical Wnt signaling pathway, and accompanying reduced expression of β catenin and integrin β4 in laminar basal epithelial cells reduces cell:cell and cell:basement membrane attachment, thus, destabilizing the laminar epidermal:dermal junction.

BackgroundCrofton weed (Ageratina adenophora) is one of the most hazardous invasive plant species, which causes serious economic losses and environmental damages worldwide. However, the sequence resource and genome information of A. adenophora are rather limited, making phylogenetic identification and evolutionary studies very difficult. Here, we report the complete sequence of the A. adenophora chloroplast (cp) genome based on Illumina sequencing.Methodology/principal findingsThe A. adenophora cp genome is 150, 689 bp in length including a small single-copy (SSC) region of 18, 358 bp and a large single-copy (LSC) region of 84, 815 bp separated by a pair of inverted repeats (IRs) of 23, 755 bp. The genome contains 130 unique genes and 18 duplicated in the IR regions, with the gene content and organization similar to other Asteraceae cp genomes. Comparative analysis identified five DNA regions (ndhD-ccsA, psbI-trnS, ndhF-ycf1, ndhI-ndhG and atpA-trnR) containing parsimony-informative characters higher than 2%, which may be potential informative markers for barcoding and phylogenetic analysis. Repeat structure, codon usage and contraction of the IR were also investigated to reveal the pattern of evolution. Phylogenetic analysis demonstrated a sister relationship between A. adenophora and Guizotia abyssinica and supported a monophyly of the Asterales.ConclusionWe have assembled and analyzed the chloroplast genome of A. adenophora in this study, which was the first sequenced plastome in the Eupatorieae tribe. The complete chloroplast genome information is useful for plant phylogenetic and evolutionary studies within this invasive species and also within the Asteraceae family.

Green fluorescent protein (GFP) and its derivatives are the most widely used molecular reporters for live cell imagining. The development of organelle-specific fusion fluorescent proteins improves the labeling resolution to a higher level. Here we generate a R26 dual fluorescent protein reporter mouse, activated by Cre-mediated DNA recombination, labeling target cells with a chromatin-specific enhanced green fluorescence protein (EGFP) and a plasma membrane-anchored monomeric cherry fluorescent protein (mCherry). This dual labeling allows the visualization of mitotic events, cell shapes and intracellular vesicle behaviors. We expect this reporter mouse to have a wide application in developmental biology studies, transplantation experiments as well as cancer/stem cell lineage tracing.

Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.

Purpose: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore, functional single nucleotide polymorphisms (SNPs) in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy. However, few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients., Experimental Design: We genotyped by the TaqMan assay three common, potentially functional ERCC1 (rs3212986) and ERCC2 SNPs (rs13181 and rs1799793) in 360 gastric cancer patients. We used both Kaplan-Meier tests and Cox proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical outcomes., Results: We found that, compared with ERCC2 rs1799793 GG+AG genotypes, the homozygous variant AA genotype was associated with significantly poorer overall survival (OS) (AA vs. GG+AG, log-rank P=0.012) and significantly higher risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to 3.56; P=0.004). In combined analyses, patients with any one of the three unfavorable genotypes (i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793 AA) had statistically significant hazards of poor prognosis (Adjusted HR, 1.54; 95% CI, 1.06 to 2.25; P=0.025), compared with those without any unfavorable genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986) had a significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011), compared with the common haplotype G-T-G., Conclusion: ERCC1 and ERCC2 functional SNPs may jointly affect OS in Caucasian gastric cancer patients. Additional large prospective studies are essential to confirm our findings.

Background: TNFAIP2 is a crucial gene involved in apoptosis. Single nucleotide polymorphisms (SNPs) in its miRNA binding sites could modulate functions of the miRNA-target genes and thus risk of cancers. In this study, we investigated associations between potentially functional SNPs in the miRNA binding sites of the 3'UTR of TNFAIP2 and gastric cancer risk in a US population., Methods: We conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. We genotyped four selected TNFAIP2 SNPs (rs8126 T>C, rs710100 G>A, rs1052912 G>A and rs1052823 G>T) and used the logistic regression analysis to assess associations of these SNPs with cancer risk., Results: The rs8126 CC genotype was associated with a significantly elevated risk of gastric cancer (adjusted OR = 2.00, 95% CI = 1.09-3.64 and P = 0.024), compared with the combined rs8126 TT+TC genotypes, particularly in current drinkers. However, none of other TNFAIP2 SNPs was associated with risk of gastric cancer., Conclusions: Our data suggested that the TNFAIP2 miRNA binding site rs8126 T>C SNP may be a marker for susceptibility to gastric cancer, and this finding requires further validation by larger studies.

In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual's DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln) and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu) exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P(trend) = 0.030). Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36-0.98 and adjusted OR = 0.47, 95% CI: 0.26-0.86, respectively; P(trend) = 0.012) among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512). Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression.

Background: Excision repair cross-complementation group 4 gene (ERCC4/XPF) plays an important role in nucleotide excision repair and participates in removal of DNA interstrand cross-links and DNA double-strand breaks. Single nucleotide polymorphisms (SNPs) in ERCC4 may impact repair capacity and affect cancer susceptibility., Methodology/principal Findings: In this case-control study, we evaluated associations of four selected potentially functional SNPs in ERCC4 with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,040 non-Hispanic white patients with SCCHN and 1,046 cancer-free matched controls. We found that the variant GG genotype of rs2276466 was significantly associated with a decreased risk of SCCHN (OR = 0.69, 95% CI 0.50-0.96), and that the variant TT genotype of rs3136038 showed a borderline significant decreased risk with SCCHN (OR = 0.76, 95% CI: 0.58-1.01) in the recessive model. Such protective effects were more evident in oropharyngeal cancer (OR = 0.61, 95% CI: 0.40-0.92 for rs2276466; OR = 0.69, 95% CI: 0.48-0.98 for rs3136038). No significant associations were found for the other two SNPs (rs1800067 and rs1799798). In addition, individuals with the rs2276466 GG or with the rs3136038 TT genotypes had higher levels of ERCC4 mRNA expression than those with the corresponding wild-type genotypes in 90 Epstein-Barr virus-transformed lymphoblastoid cell lines derived from Caucasians., Conclusions: These results suggest that these two SNPs (rs2276466 and rs3136038) in ERCC4 may be functional and contribute to SCCHN susceptibility. However, our findings need to be replicated in further large epidemiological and functional studies.

Background: The functional polymorphism (rs1800566) in the NQO1 gene, a 609C>T substitution, leading to proline-to-serine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results., Methodology/principal Findings: We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C>T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95% CI = 1.01 - 1.19, P(heterogeneity) = 0.27, I(2) = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 - 1.20, P(heterogeneity) = 0.14; I(2) = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies., Conclusions: This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyses suggest that further larger studies are needed, especially for non-colorectal GI cancers in Caucasians and GI cancers in Asians.

The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 -135G>C/rs1801320 and -172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 -135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31-0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 -135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14-2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02-2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 -135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings.