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Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

Background: Lipotoxicity has been implicated in diabetic kidney disease (DKD). However, the role of high glucose levels in DKD and the underlying renal protective mechanisms of GLP-1 receptor agonists (GLP-1RAs) remain unclear., Methods: To investigate cholesterol accumulation, pyroptosis in glomerular endothelial cells (GEnCs), and the renal protective mechanisms of GLP-1RAs, we used various techniques, including RT-qPCR, Oil Red O staining, Western blotting, lactate dehydrogenase (LDH) activity assays, circRNA microarrays, bioinformatics analysis, gain and loss-of-function experiments, rescue experiments, and luciferase assays. Additionally, in vivo experiments were conducted using C57BL/6J and ApoE-deficient (ApoE-/-) mice., Results: GEnCs exposed to high glucose exhibited reduced cholesterol efflux, which was accompanied by downregulation of ATP-binding cassette transporter A1 (ABCA1) expression, cholesterol accumulation, and pyroptosis. Circ8411 was identified as a regulator of ABCA1, inhibiting miR-23a-5p through its binding to the 3'UTR. Additionally, higher glucose levels decreased circ8411 expression by inhibiting RXRα. GLP-1RAs effectively reduced cholesterol accumulation and cell pyroptosis by targeting the RXRα/circ8411/miR-23a-5p/ABCA1 pathway. In diabetic ApoE-/- mice, renal structure and function were impaired, with resulted in increased cholesterol accumulation and pyroptosis; however, GLP-1RAs treatment reversed these detrimental changes., Conclusions: These findings suggest that the RXRα/circ8411/miR-23a-5p/ABCA1 pathway mediates the contribution of high glucose to lipotoxic renal injury. Targeting this pathway may represent a potential therapeutic strategy for patients with DKD and hypercholesterolemia. Moreover, GLP-1RAs may provide renal protective effects by activating this pathway., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Solid oxide fuel cells (SOFCs) are vital for alternative energy, powering motors effi-ciently. They offer fuel versatility and waste heat recovery, making them ideal for various applications. Optimizing interconnector structures is crucial for SOFC advancement. This paper introduces a novel 2D simulation model for interconnector SOFCs, aiming to enhance their performance. We initially construct a single half-cell model for a conventional interconnector SOFC, ensuring model accuracy. Subsequently, we propose an innovative interconnector SOFC model, which outperforms the conventional counterpart in various aspects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Breast cancer is a major health problem with high mortality rates. Early detection of breast cancer will promote treatment. A technology that determines whether a tumor is benign desirable. This article introduces a new method in which deep learning is used to classify breast cancer., Methods: A new computer-aided detection (CAD) system is presented to classify benign and malignant masses in breast tumor cell samples. In the CAD system, (1) for the pathological data of unbalanced tumors, the training results are biased towards the side with the larger number of samples. This paper uses a Conditional Deep Convolution Generative Adversarial Network (CDCGAN) method to generate small samples by orientation data set to solve the imbalance problem of collected data. (2) For the high-dimensional data redundancy problem, this paper proposes an integrated dimension reduction convolutional neural network (IDRCNN) model, which solves the high-dimensional data dimension reduction problem of breast cancer and extracts effective features. The subsequent classifier found that by using the IDRCNN model proposed in this paper, the accuracy of the model was improved., Results: Experimental results show that IDRCNN combined with the model of CDCGAN model has superior classification performance than existing methods, as revealed by sensitivity, area under the curve (AUC), ROC curve and accuracy, recall, sensitivity, specificity, precision,PPV,NPV and f-values analysis., Conclusion: This paper proposes a Conditional Deep Convolution Generative Adversarial Network (CDCGAN) which can solve the imbalance problem of manually collected data by directionally generating small sample data sets. And an integrated dimension reduction convolutional neural network (IDRCNN) model, which solves the high-dimensional data dimension reduction problem of breast cancer and extracts effective features., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hyperuricaemic nephropathy (HN) is a common clinical complication of hyperuricaemia (HUA) and poses a huge threat to human health. Hence, we aimed to prospectively investigate the dysregulated genes, pathways and networks involved in HN by performing whole transcriptome sequencing using RNA sequencing. Six kidney samples from HN group (n = 3) and a control group (n = 3) were obtained to conduct RNA sequencing. To disclose the relevant signalling pathways, we conducted the analysis of differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A competitive endogenous RNA (ceRNA) network was established to reveal the interactions between lncRNAs, circRNAs, mRNAs and miRNAs and investigate the potential mechanisms of HN. Ultimately, 2250 mRNAs, 306 lncRNAs, 5 circRNAs, and 70 miRNAs were determined to be significantly differentially expressed in the HN group relative to the control group. We further authenticated 8 differentially expressed (DE)-ncRNAs by quantitative real-time polymerase chain reaction, and these findings were in accordance with the sequencing results. The analysis results evidently showed that these DE-ncRNAs were significantly enriched in pathways related to inflammatory reaction. In conclusion, HUA may generate abnormal gene expression changes and regulate signalling pathways in kidney samples. Potentially related genes and pathways involved in HN were identified., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Postpartum uterine infection in dairy cows is commonly caused by pathogenic bacteria such as Escherichia coli (E. coli). Progesterone elicits immunosuppressive function within bovine endometrium, and has been suggested to be related to postpartum uterine infection. Endometrial stroma is exposed to bacteria due to the disruption of epithelium during parturition, but the effect and mechanism of progesterone on innate immune response of stromal cells has not been reported. This study evaluated the impact of progesterone on inflammatory response of primary endometrial stromal cells stimulated by lipopolysaccharide or heat-killed E. coli. Quantitative PCR analysis revealed that progesterone repressed mRNA induction of IL1B, IL6, TNF, CXCL8, NOS2, and PTGS2 in stromal cells in response to lipopolysaccharide or E. coli challenge. Consistently, Western blot and immunofluorescence staining results showed that progesterone suppressed lipopolysaccharide- or E. coli-induced MAPK and NF-κB activations characterized with decreased phosphorylations of ERK1/2, JNK, P38, IκBα, and P65, and inhibition of P65 nuclear translocation. In unstimulated stromal cells, progesterone alone did not affect the mRNA transcription for IL6, TNF, CXCL8, NOS2, and PTGS2, and the signaling cascade of MAPK and NF-κB, but decreased IL1B mRNA expression. These results revealed that the anti-inflammatory effect of progesterone in lipopolysaccharide- or E. coli-challenged endometrial stromal cells was probably mediated through MAPK and NF-κB pathways., Competing Interests: The authors have declared that no competing interests exist.

Background: Adverse childhood experiences (ACEs) are linked to numerous health conditions but understudied in multiple sclerosis (MS). This study's objective was to test for the association between ACEs and MS risk and several clinical outcomes., Methods: We used a sample of adult, non-Hispanic MS cases (n = 1422) and controls (n = 1185) from Northern California. Eighteen ACEs were assessed including parent divorce, parent death, and abuse. Outcomes included MS risk, age of MS onset, Multiple Sclerosis Severity Scale score, and use of a walking aid. Logistic and linear regression estimated odds ratios (ORs) (and beta coefficients) and 95% confidence intervals (CIs) for ACEs operationalized as any/none, counts, individual events, and latent factors/patterns., Results: Overall, more MS cases experienced ≥1 ACE compared to controls (54.5% and 53.8%, respectively). After adjusting for sex, birthyear, and race, this small difference was attenuated (OR = 1.01, 95% CI: 0.87, 1.18). There were no trends of increasing or decreasing odds of MS across ACE count categories. Consistent associations between individual ACEs between ages 0-10 and 11-20 years and MS risk were not detected. Factor analysis identified five latent ACE factors, but their associations with MS risk were approximately null. Age of MS onset and other clinical outcomes were not associated with ACEs after multiple testing correction., Conclusion: Despite rich data and multiple approaches to operationalizing ACEs, no consistent and statistically significant effects were observed between ACEs with MS. This highlights the challenges of studying sensitive, retrospective events among adults that occurred decades before data collection., Competing Interests: The authors have declared that no competing interests exist.

The purposes are to monitor the nitrogen utilization efficiency of crops and intelligently evaluate the absorption of nutrients by crops during the production process. The research object is Chinese cabbage. The Chinese cabbage population with different agricultural parameters is constructed through different densities and nitrogen fertilizer application rates based on digital image processing technology, and an estimation NC (Nitrogen Content) model is established. The population is classified through the K-Means Clustering algorithm using the feature extraction method, and the Chinese cabbage population quality BPNN (Backpropagation Neural Network) model is constructed. The nonlinear mapping relationship between different agricultural parameters and population quality, and the contribution rate of each indicator, are studied. The nitrogen utilization of Chinese cabbage is monitored effectively. Results demonstrate that the proposed NC estimation model has correlation coefficients above 0.70 in different growth stages. This model can accurately estimate the NC of the Chinese cabbage population. The results of the Chinese cabbage population quality BPNN model show that the population planting density based on the seedling number is reasonable. The constructed population quality evaluation model has a high R2 value and a comparatively low RMSE (Root Mean Square Error) value for the quality evaluation of Chinese cabbage in different periods, showing that it applies to evaluate the population quality of Chinese cabbage in different growth stages. The constructed nitrogen utilization model and quality evaluation model can monitor the nutrient utilization of crops in different growth stages, ascertain the agricultural characteristics of other yield groups in different growth stages, and clarify the performance of agricultural parameters in different growth stages. The above results can provide some ideas for crop growth intelligent detection., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To derive and validate a concise prediction model estimating the 10-year risk for type 2 diabetes (T2DM) in China., Methods: A total of 11494 subjects from the China Health and Nutrition Survey recorded from 2004 to 2015 were analyzed and only 6023 participants were enrolled in this study. Four logistic models were analyzed using the derivation cohort. Methods of calibration and discrimination were used for the validation cohort., Results: In the derivation cohort, 257 patients were identified from a total of 4498 cases. In the validation cohort, 92 patients were identified from a total of 1525 cases. Four models performed nicely for both calibration and discrimination. The AUC in the derivation cohort for models A, B, C and D were 0.788 (0.761-0.816), 0.807 (0.780-0.834), 0.905 (0.879-0.932) and 0.882 (0.853-0.912), respectively. The Youden index for models A, B, C and D were 1.46, 1.48, 1.67 and 1.65, respectively. Model C showed the highest sensitivity and model D showed the highest specificity., Conclusion: Models A and B were non-invasive and can be used to identify high-risk patients for broad screening. Models C and D may be used to provide more accurate assessments of diabetes risk. Furthermore, model C showed the best performance for predicting T2DM risk and identifying individuals who are in need of interventions, current approach improvement and additional follow-up., Competing Interests: The authors have declared that no competing interests exist.

Endothelial cells are a primary site of leukocyte recruitment during inflammation. An increase in tumor necrosis factor-alpha (TNFa) levels as a result of infection or some autoimmune diseases can trigger this process. Several autoimmune diseases are now treated with TNFa inhibitors. However, genomic alterations that occur as a result of TNF-mediated inflammation are not well understood. To investigate molecular targets and networks resulting from increased TNFa, we measured DNA methylation and gene expression in 40 human umbilical vein endothelial cell primary cell lines before and 24 hours after stimulation with TNFa via microarray. Weighted gene co-expression network analysis identified 15 gene groups (modules) with similar expression correlation patterns; four modules showed a strong association with TNFa treatment. Genes in the top TNFa-associated module were all up-regulated, had the highest proportion of hypomethylated regions, and were associated with 136 Disease Ontology terms, including autoimmune/inflammatory, infectious and cardiovascular diseases, and cancers. They included chemokines CXCL1, CXCL10 and CXCL8, and genes associated with autoimmune diseases including HLA-C, DDX58, IL4, NFKBIA and TNFAIP3. Cardiovascular and metabolic disease genes, including APOC1, ACLY, ELOVL6, FASN and SCD, were overrepresented in a module that was not associated with TNFa treatment. Of 223 hypomethylated regions identified, several were in promoters of autoimmune disease GWAS loci (ARID5B, CD69, HDAC9, IL7R, TNIP1 and TRAF1). Results reveal specific gene groups acting in concert in endothelial cells, delineate those driven by TNFa, and establish their relationship to DNA methylation changes, which has strong implications for understanding disease etiology and precision medicine approaches., Competing Interests: The authors have declared that no competing interests exist.

The brown planthopper, Nilaparvata lugens (Stål), severely damages rice production and develops high level resistance to several classes of insecticides. To find potential insecticidal resources is always important. As an environmentally friendly compound, aconitine exhibits potential pesticide features. In the present study, the pesticide and knockdown effects of aconitine were first tested on the brown planthopper. The results showed that the knockdown rates for an aconitine concentration of 200 ppm was 83.6%. The insecticidal LD50 was 22.68 ng/pest (95% CI, 17.75-28.99). The molecular mechanisms responding to aconitine application were analyzed through transcriptional sequencing. Compared to that of the knockdown nymphs of the brown planthoppers, the enzymes CYP3A4, UDP-glucuronosyltransferase (UGT), GST, carboxylesterase (EC3.1.1.1), and GABAergic synapse were up-regulated. We inferred that aconitine might be neurotoxic to the brown planthoppers, and the conscious nymphs resist the drug neurotoxicity through the upregulation of CYP3A4, UGT, and GABA receptor mutation. Although aconitine is not safe for mammals, it may be a leading compound to develop novel insecticides., Competing Interests: The authors have declared that no competing interests exist.

In this paper, we put forward a real-time multiple GPUs (multi-GPU) accelerated virtual-reality interaction simulation framework where the reconstructed objects from camera images interact with virtual deformable objects. Firstly, based on an extended voxel-based visual hull (VbVH) algorithm, we design an image-based 3D reconstruction platform for real objects. Then, an improved hybrid deformation model, which couples the geometry constrained fast lattice shape matching method (FLSM) and total Lagrangian explicit dynamics (TLED) algorithm, is proposed to achieve efficient and stable simulation of the virtual objects' elastic deformations. Finally, one-way virtual-reality interactions including soft tissues' virtual cutting with bleeding effects are successfully simulated. Moreover, with the purpose of significantly improving the computational efficiency of each time step, we propose an entire multi-GPU implementation method of the framework using compute unified device architecture (CUDA). The experiment results demonstrate that our multi-GPU accelerated virtual-reality interaction framework achieves real-time performance under the moderate calculation scale, which is a new effective 3D interaction technique for virtual reality applications., Competing Interests: The authors have declared that no competing interests exist.

To solve the problem of the deadline-constrained task scheduling in the cloud computing system, this paper proposes a deadline-constrained scheduling algorithm for cloud computing based on the driver of dynamic essential path (Deadline-DDEP). According to the changes of the dynamic essential path of each task node in the scheduling process, the dynamic sub-deadline strategy is proposed. The strategy assigns different sub-deadline values to every task node to meet the constraint relations among task nodes and the user's defined deadline. The strategy fully considers the dynamic sub-deadline affected by the dynamic essential path of task node in the scheduling process. The paper proposed the quality assessment of optimization cost strategy to solve the problem of selecting server for each task node. Based on the sub-deadline urgency and the relative execution cost in the scheduling process, the strategy selects the server that not only meets the sub-deadline but also obtains much lower execution cost. In this way, the proposed algorithm will make the task graph complete within its deadline, and minimize its total execution cost. Finally, we demonstrate the proposed algorithm via the simulation experiments using Matlab tools. The experimental results show that, the proposed algorithm produces remarkable performance improvement rate on the total execution cost that ranges between 10.3% and 30.8% under meeting the deadline constraint. In view of the experimental results, the proposed algorithm provides better-quality scheduling solution that is suitable for scientific application task execution in the cloud computing environment than IC-PCP, DCCP and CD-PCP., Competing Interests: The authors have declared that no competing interests exist.

Heterogeneity is prevalent in cancer both between and within individuals. Although a few studies have identified several circulating microRNAs (miRNAs) for cancer diagnosis, the complete plasma miRNA profile for hepatocellular carcinoma (HCC) remains undefined, and whether the plasma miRNA profiles are heterogeneous is unknown. Here, we obtained individualized plasma miRNA profiles of both healthy subjects and HCC patients via genome-wide deep sequencing. Compared with the highly stable miRNA profile of the healthy subjects, the profile of the HCC patients was highly variable. Seven miRNAs were optimized as potential plasma-based biomarkers for HCC diagnosis. Combined with the clinical data of The Cancer Genome Atlas (TCGA) cohort, three out of the seven miRNAs were correlated with the survival of the HCC patients. To investigate the effect of cancer cells on the plasma miRNAs profile, we compared the most differentially expressed miRNAs between plasma and tissues. Furthermore, miRNAseq data of HCC patients from TCGA were recruited for comparisons. We found that the differences between plasma and tissue were inconsistent, suggesting that other cells in addition to cancer cells also contribute to plasma miRNAs. Using two HCC cancer cell lines, we examined the levels of seven differentially expressed miRNAs. The reverse direction of certain miRNAs alterations between cancer cells and media further confirmed that miRNAs may be selectively pump out by cancer cells., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice., Methods: We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval., Results: The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2., Conclusions: These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice.

Changes in the hydrological conditions of coastal wetlands may potentially affect the role of wetlands in the methane (CH4) cycle. In this study, the CH4 production potential and emissions from restored coastal reed wetlands at different water levels were examined in eastern China at a field scale in two phenological seasons. Results showed that the total CH4 flux from reeds at various water levels were positive, indicating that they were "sources" of CH4. During the peak growing season, CH4 flux from reeds was greater than that during the spring thaw. CH4 flux from reeds in inundated conditions was greater than that in non-inundated conditions. The CH4 production potential during the peak growing season was far greater than that during the spring thaw. However, the effect of water level on wetland CH4 production potential differed among seasons. The correlations among CH4 production potential, soil properties and CH4 flux change at different water level. These results demonstrate that water level was related to CH4 production and CH4 flux. The growing season also plays a role in CH4 fluxes. Controlling the hydrological environment in restored wetlands has important implications for the maintenance of their function as carbon sinks.

Choroid has been proposed to participate in the regulation of light refraction by changing its thickness. The present study aims to analyze the characteristics of choroidal thickness (CT), and its correlation with refractive error, axial length and age in young ametropia. A total of 51 subjects (102 eyes), aged from 5 to 18 years old (mean age 10.04 ±2.78 years), with ametropia were included in the study. Choroidal imaging was obtained by enhanced depth imaging (EDI) of spectral domain Optical Coherence Tomography (OCT). CT was horizontally measured at 5 locations in across fovea with 1mm interval. We found that the spherical equivalent refractive diopter was from -7.25D to 1.6D (mean, -1.61D±1.82D), the mean axial length was 24.14mm±1.14mm. The closer to the optic disc the thinner the choroid is. CT between fovea and disc showed better correlation with refractive error (p< 0,01), axial length (p<0.01) and age (P<0.05) than those temporal to fovea. Our results indicated that the choroid is least thick around the optic disc. Thickness between fovea and optic disc is significantly associated with refractive error, axial length and age in growing adolescences. This result may help us understand the function of choroid during ametropic progression.

Background: The factors influencing the prognosis of acute kidney injury (AKI) were analyzed in a group of elderly AKI patients to determine the markers of early prognosis., Methods: A total of 258 patients were screened, and 201 patients were enrolled in the study. Eventually, 184 AKI patients were included in the study, including 79 elderly AKI patients (≥60 years old). During one year of follow-up, renal function changes were observed, and the risk factors that influenced the prognosis of AKI were analyzed., Results: When AKI occurred, the urine kidney injury molecule-1 (uKIM-1) level was significantly higher in the progressive deterioration of renal function group than in the renal function stable group. The ROC curve analysis revealed that the area under the curve for poor progressive deterioration of renal function as predicted by the uKIM-1 level was 0.681. At a cutoff point of 2.46 ng/mg, the sensitivity was 71.9% and the specificity was 70.0%. In elderly AKI patients, uKIM-1 levels exceeding 2.46 ng/mg were positively associated with poor kidney prognosis., Conclusions: Elderly AKI patients are at risk of developing progressive deterioration of renal function. In elderly AKI patients, the high uKIM-1 level may predict the prognosis of kidney function and may be used as an early screening indicator of poor kidney prognosis., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to investigate the association of serum betatrophin with the status and progression of nonalcoholic fatty liver disease (NAFLD)., Methods: A total of 249 subjects who received ultrasonic examination of liver fat content (LFC) were recruited. Anthropometric and biochemical examinations were performed. Serum betatrophin was measured by ELISA., Results: Compared with control group, serum betatrophin significantly increased in NAFLD group (P < 0.05). There was significant difference in serum betatrophin among control, low liver fat content (LLFC), and high liver fat content (HLFC) groups (P < 0.01). After adjustment for gender, age, BMI, FPG and HbA1c, the betatrophin positively correlated with LFC (r = 0.185, P < 0.01) and TG (r = 0.195, P < 0.01). Stepwise multiple regression analysis indicated serum betatrophin was independently related to LFC (P < 0.05). Multivariate logistic regression analysis revealed subjects in the highest tertile of serum betatrophin had higher odds of having NAFLD after adjustment for traditional NAFLD risk factors (OR = 2.88, 95%CI: 1.15-7.19) (P<0.05)., Conclusion: Serum betatrophin is an independent risk factor for NAFLD and potential non-invasive marker for its progression. Serum betatrophin may be helpful for the early diagnosis of NAFLD and improvement of its prognosis., Competing Interests: The authors have declared that no competing interests exist.

Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment., Competing Interests: Dr. Sven-Eric Jordt serves on the Scientific Advisory Board of Hydra Biosciences LLC (Cambridge, MA), a biopharmaceutical company developing TRP ion channel inhibitors for the treatment of pain and inflammation.

To solve the problem of task scheduling in the cloud computing system, this paper proposes a scheduling algorithm for cloud computing based on the driver of dynamic essential path (DDEP). This algorithm applies a predecessor-task layer priority strategy to solve the problem of constraint relations among task nodes. The strategy assigns different priority values to every task node based on the scheduling order of task node as affected by the constraint relations among task nodes, and the task node list is generated by the different priority value. To address the scheduling order problem in which task nodes have the same priority value, the dynamic essential long path strategy is proposed. This strategy computes the dynamic essential path of the pre-scheduling task nodes based on the actual computation cost and communication cost of task node in the scheduling process. The task node that has the longest dynamic essential path is scheduled first as the completion time of task graph is indirectly influenced by the finishing time of task nodes in the longest dynamic essential path. Finally, we demonstrate the proposed algorithm via simulation experiments using Matlab tools. The experimental results indicate that the proposed algorithm can effectively reduce the task Makespan in most cases and meet a high quality performance objective.

Long-term manure application is recognized as an efficient management practice to enhance soil organic carbon (SOC) accumulation and nitrogen (N) mineralization capacity. A field study was established in 1979 to understand the impact of long-term manure and/or chemical fertilizer application on soil fertility in a continuous maize cropping system. Soil samples were collected from field plots in 2012 from 9 fertilization treatments (M0CK, M0N, M0NPK, M30CK, M30N, M30NPK, M60CK, M60N, and M60NPK) where M0, M30, and M60 refer to manure applied at rates of 0, 30, and 60 t ha(-1) yr(-1), respectively; CK indicates no fertilizer; N and NPK refer to chemical fertilizer in the forms of either N or N plus phosphorus (P) and potassium (K). Soils were separated into three particle-size fractions (2000-250, 250-53, and <53 μm) by dry- and wet-sieving. A laboratory incubation study of these separated particle-size fractions was used to evaluate the effect of long-term manure, in combination with/without chemical fertilization application, on the accumulation and mineralization of SOC and total N in each fraction. Results showed that long-term manure application significantly increased SOC and total N content and enhanced C and N mineralization in the three particle-size fractions. The content of SOC and total N followed the order 2000-250 μm > 250-53 μm > 53 μm fraction, whereas the amount of C and N mineralization followed the reverse order. In the <53 μm fraction, the M60NPK treatment significantly increased the amount of C and N mineralized (7.0 and 10.1 times, respectively) compared to the M0CK treatment. Long-term manure application, especially when combined with chemical fertilizers, resulted in increased soil microbial biomass C and N, and a decreased microbial metabolic quotient. Consequently, long-term manure fertilization was beneficial to both soil C and N turnover and microbial activity, and had significant effect on the microbial metabolic quotient.

Neutrophil infiltration is the characteristic pathological feature of M. pneumoniae pneumonia (MPP). This study aimed to explore the associations among neutrophil activity, clinical presentation, and role of the M. pneumoniae/interleukin-8 (IL-8)/neutrophil axis in the pathogenesis of MPP. A total of 42 patients with MPP were prospectively enrolled in the study. Neutrophil activity, including matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), and neutrophil elastase (NE), were measured. Clinical information was collected for all patients and control group. In vitro, IL-8 production was measured at different time points after M. pneumoniae infection of bronchial epithelial cells, and neutrophil activity was analyzed after IL-8 stimulation. The percentage of neutrophil in the bronchoalveolar lavage fluid was higher in the group of patients with high levels of M. pneumoniae DNA than in those with low levels of M. pneumoniae DNA (P < 0.05). IL-8, MMP-9, and NE in patients with MPP significantly increased compared with controls and decreased after treatment (P < 0.05). MPO and MMP-9 were associated with duration of fever (r = 0.332, P < 0.05) and length of stay (r = 0.342, P < 0.05), respectively. In vitro, M. pneumoniae induced IL-8 production by bronchial epithelial cells in a time dependent manner. MPO, MMP-9 and NE production by neutrophils significantly increased compared with medium controls after IL-8 stimulation. In summary, the M. pneumoniae/IL-8/neutrophil axis likely plays a vital role in the pathogenesis of MPP.

Soil labile organic carbon and soil enzymes play important roles in the carbon cycle of coastal wetlands that have high organic carbon accumulation rates. Soils under three vegetations (Phragmites australis, Spartina alterniflora, and Scirpusm mariqueter) as well as bare mudflat in Hangzhou Bay wetland of China were collected seasonally. Seasonal dynamics and correlations of soil labile organic carbon fractions and soil enzyme activities were analyzed. The results showed that there were significant differences among vegetation types in the contents of soil organic carbon (SOC) and dissolved organic carbon (DOC), excepting for that of microbial biomass carbon (MBC). The P. australis soil was with the highest content of both SOC (7.86 g kg-1) and DOC (306 mg kg-1), while the S. mariqueter soil was with the lowest content of SOC (6.83 g kg-1), and the bare mudflat was with the lowest content of DOC (270 mg kg-1). Soil enzyme activities were significantly different among vegetation types except for urease. The P. australis had the highest annual average activity of alkaline phosphomonoesterase (21.4 mg kg-1 h-1), and the S. alterniflora had the highest annual average activities of β-glycosidase (4.10 mg kg-1 h-1) and invertase (9.81 mg g-1 24h-1); however, the bare mudflat had the lowest activities of alkaline phosphomonoesterase (16.2 mg kg-1 h-1), β-glycosidase (2.87 mg kg-1 h-1), and invertase (8.02 mg g-1 24h-1). Analysis also showed that the soil labile organic carbon fractions and soil enzyme activities had distinct seasonal dynamics. In addition, the soil MBC content was significantly correlated with the activities of urease and β-glucosidase. The DOC content was significantly correlated with the activities of urease, alkaline phosphomonoesterase, and invertase. The results indicated that vegetation type is an important factor influencing the spatial-temporal variation of soil enzyme activities and labile organic carbon in coastal wetlands.

Objectives: The optimal treatment of hepatitis C virus (HCV) genotype 6 is unclear owing to its limited geographic distribution. Because of a high predictive value of rapid virological response (RVR) for sustained virological response (SVR), we conducted an open-label randomized controlled trial to compare 24- and 48-week peginterferon/ribavirin combination therapy for patients with HCV genotype 6 in Southern China who achieved an RVR., Methods and Findings: Treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 6 were treated with pegylated interferon α-2a (180 μg/week) and ribavirin (800-1,200 mg, according to weight) for 4 weeks. Patients who achieved an RVR, which was defined as HCV RNA negativity at week 4 (<50 IU), were randomized to receive either an additional 20 or 44 weeks of treatment (24- and 48-week treatment groups, respectively). The primary outcome measure was SVR. From January 2011 to June 2014, 152(152/210, 72.4%) patients with HCV genotype 6a and RVR were randomized 1:1 to the 24- or 48-week treatment group. The SVR rates in the 24- and 48-week groups in the intention-to-treat analysis were 90.8% (69/76) and 88.2% (67/76), respectively; those in the per-protocol analysis were 95.7% (67/70) and 97.0% (64/66), respectively. More patients in the 48-week group had anemia (46.1% vs. 28.9%, P = 0.03), but other adverse events were comparable between the groups. The limitation of the present study was that only patients from Southern China were enrolled which may inhibit the extensive application of the findings., Conclusion: Twenty-four weeks of peginterferon/ribavirin combination therapy was non-inferior to 48 weeks in patients with HCV genotype 6a in Southern China who achieved an RVR., Trial Registration: ClinicalTrials.gov NCT01263860.

Introduction: Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN., Methods: For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry., Results: Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages., Conclusion: Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an important role in disease progression of LN.

Background and Objectives: Renal relapse is a very common manifestation of IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored., Design and Patients: Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study., Results: Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5%) of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4%) in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6%) in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP) was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling on the validation cohort., Conclusions: This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse.

Tuyuhun and Tubo were two important states that thrived in north-western China during AD 311-900 in parallel with the Han Chinese dynasties of Sui and Tang periods. The Reshui Tomb Cluster located in Dulan County of the north-eastern Tibetan Plateau is an important cultural relic of the Tuyuhun-Tubo age. The official excavations of the Reshui tombs were regarded as top events in archaeology in the 1980s and 1990s in China. The Reshui-1 Tomb is the largest one among the tombs in the area. Since its excavation, there have been debates on whether the owner of the tomb belonged to the Tuyuhun or Tubo ethnicity. Therefore, accurately dating the Reshui-1 Tomb has a critical place in studying the Tubo and Tuyuhun histories. We collected 7 discs and 11 increment cores of Qilian juniper (Juniperus przewalskii Kom.) from the exposed and fallen beams of the roof of the Reshui-1Tomb. The lengths of the 16 tree-ring records are between 69 and 152 years. Based on a previously developed master dating chronology using Qilian juniper samples from the eastern Qaidam Basin, the calendar dates of the 16 specimens were determined by the COFECHA program and visual dating procedure. The average inter-series correlation among the dated sample series is 0.696, indicating good quality of cross-dating. The year of the outermost rings is AD 715 for the 7 discs and 4 out of the 9 increment cores. Moreover, the ring-width variations of the samples are consistent with the existing chronologies from the region. The presence of late-wood of AD 715 in the samples indicated that the Reshui-1 Tomb was completed in late AD 715 or early 716, which means that the Reshui-1 Tomb was finished in the Tubo age. This date provides direct evidence for archaeologists to determine the owner's ethnicity and identify of the Reshui-1 Tomb.

Tibet makes up the majority of the Qinghai-Tibet Plateau, often referred to as the roof of the world. Its complex landforms, physiognomy, and climate create a special heterogeneous environment for mosses. Each moss species inhabits its own habitat and ecological niche. This, in combination with its sensitivity to environmental change, makes moss species distribution a useful indicator of vegetation alteration and climate change. This study aimed to characterize the diversity and distribution of Didymodon (Pottiaceae) in Tibet, and model the potential distribution of its species. A total of 221 sample plots, each with a size of 10 × 10 m and located at different altitudes, were investigated across all vegetation types. Of these, the 181 plots in which Didymodon species were found were used to conduct analyses and modeling. Three noteworthy results were obtained. First, a total of 22 species of Didymodon were identified. Among these, Didymodon rigidulus var. subulatus had not previously been recorded in China, and Didymodon constrictus var. constrictus was the dominant species. Second, analysis of the relationships between species distributions and environmental factors using canonical correspondence analysis revealed that vegetation cover and altitude were the main factors affecting the distribution of Didymodon in Tibet. Third, based on the environmental factors of bioclimate, topography and vegetation, the distribution of Didymodon was predicted throughout Tibet at a spatial resolution of 1 km, using the presence-only MaxEnt model. Climatic variables were the key factors in the model. We conclude that the environment plays a significant role in moss diversity and distribution. Based on our research findings, we recommend that future studies should focus on the impacts of climate change on the distribution and conservation of Didymodon.

The Grain to Green Project (GGP) is an unprecedented land restoration action in China. The project converted large areas (ca 10 million ha) of steep-sloped/degraded farmland and barren land into forest and grassland resulting in ecological benefits such as a reduction in severe soil erosion. It may also affect soil microorganisms involved in ammonia oxidization, which is a key step in the global nitrogen cycle. The methods for restoration that are typically adopted in semi-arid regions include abandoning farmland and growing drought tolerant grass (Lolium perenne L.) or shrubs (Caragana korshinskii Kom.). In the present study, the effects of these methods on the abundance and diversity of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) were evaluated via quantitative real-time PCR, terminal restriction fragment length polymorphism and clone library analysis of amoA genes. Comparisons were made between soil samples from three restored lands and the adjacent farmland in Inner Mongolia. Both the abundance and community composition of AOB were significantly different between the restored lands and the adjacent control. Significantly lower nitrification activity was observed for the restored land. Clone library analysis revealed that all AOB amoA gene sequences were affiliated with Nitrosospira. Abundance of the populations that were associated with Nitrosospira sp. Nv6 which had possibly adapted to high concentrations of inorganic nitrogen, decreased on the restored land. Only a slight difference in the AOB communities was observed between the restored land with and without the shrub (Caragana korshinskii Kom.). A minor effect of land restoration on AOA was observed. In summary, land restoration negatively affected the abundance of AOB and soil nitrification activities, suggesting the potential role of GGP in the leaching of nitrates, and in the emission of N2O in related terrestrial ecosystems.

Warming-induced drought has widely affected forest dynamics in most places of the northern hemisphere. In this study, we assessed how climate warming has affected Picea crassifolia (Qinghai spruce) forests using tree growth-climate relationships and the normalized difference vegetation index (NDVI) along the Qilian Mountains, northeastern Tibet Plateau (the main range of Picea crassifolia). Based on the analysis on trees radial growth data from the upper tree line and the regional NDVI data, we identified a pervasive growth decline in recent decades, most likely caused by warming-induced droughts. The drought stress on Picea crassifolia radial growth were expanding from northeast to southwest and the favorable moisture conditions for tree growth were retreating along the identical direction in the study area over the last half century. Compared to the historical drought stress on tree radial growth in the 1920s, recent warming-induced droughts display a longer-lasting stress with a broader spatial distribution on regional forest growth. If the recent warming continues without the effective moisture increasing, then a notable challenge is developed for Picea crassifolia in the Qilian Mountains. Elaborate forest management is necessary to counteract the future risk of climate change effects in this region.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality. Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties. Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs., Methods: We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs. The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year., Results: Nine RCTs comprising 1666 patients met the inclusion criteria. Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01). Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective. Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates. The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups. A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049)., Conclusions: Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD. However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance. A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages.

Purpose: Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study., Methods: Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I-II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS)., Results: In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002)., Conclusions: The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer.

Aim: To explore the association of lipid ratios and triglyceride (TG) with insulin resistance (IR) in a Chinese population. We also provide the clinical utility of lipid ratios to identify men and women with IR., Methods: This cross-sectional study included 614 men and 1055 women without diabetes. Insulin resistance was defined by homeostatic model assessment of IR > 2.69. Lipid ratios included the TG/ high density lipoprotein cholesterol (HDL-C), the total cholesterol (TC)/HDL-C and the low density lipoprotein cholesterol (LDL-C)/HDL -C. Logistic regression models and accurate estimates of the area under the receiver operating characteristic (AUROC) curves were obtained., Results: In normal-weight men, none of lipid ratios nor TG was associated with IR. In overweight/obese men, normal-weight women and overweight/obese women, the TG/HDL-C, the TC/HDL-C and TG were significantly associated with IR, and the associations were independent of waist circumference. All of the AUROCs for the TG/HDL-C and TG were > 0.7. The AUROCs for TC/HDL-C ratio were 0.69-0.77. The optimal cut-offs for TG/HDL-C were 1.51 in men and 0.84 in women. The optimal cut-offs for TG were 1.78 mmol/L in men and 1.49 mmol/L in women, respectively. In men, the optimal cut-off for LDL-C/HDL-C is 3.80. In women, the optimal cut-off for LDL-C/HDL-C is 3.82., Conclusion: The TG/HDL-C, the TC/HDL-C and TG are associated with IR in overweight/obese men, normal-weight and overweight/obese women. The LDL-C/HDL-C is only associated with IR in normal-weight women. The TG/HDL-C and TG might be used as surrogate markers for assessing IR.

Objectives: To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis., Methods: A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-1), liver-type fatty acid-binding protein (uL-FABP), and neutrophil gelatinase associated lipocalin (uNGAL) were determined by enzyme-linked immunosorbent assay (ELISA). After 1 year of follow-up, the predictive values of biomarker panel for determining the prognosis of obstructive nephropathy were evaluated., Results: uKIM-1 (r = 0.823), uL-FABP (r = 0.670), and uNGAL (r = 0.720) levels were positively correlated with the serum creatinine level (all P<0.01). The levels of uKIM-1, uL-FABP, and uNGAL were higher in the renal function deterioration group than in the renal function stable group. Cox regression analysis revealed that the 72-h postoperative uKIM-1 level and the preoperative and 72-h postoperative uL-FABP levels were all risk factors for renal function deterioration (all P<0.01). The area under the curve of Receiver Operating Characteristic(ROC-AUCs) of 72-h postoperative uKIM-1, preoperative uL-FABP, and 72-h postoperative uL-FABP were 0.786, 0.911, and 0.875, respectively. When the combined preoperative uKIM-1, uL-FABP, and uNGAL levels or combined 72-h postoperative uKIM-1, uL-FABP, and uNGAL levels were considered, the accuracy of prediction for renal prognosis was markedly increased, with an ROC-AUC of 0.967 or 0.964, respectively. Kaplan-Meier survival curve analysis demonstrated that a 72-h postoperative uKIM-1>96.69 pg/mg creatinine (Cr), a preoperative uL-FABP>154.62 ng/mg Cr, and a 72-h postoperative uL-FABP>99.86 ng/mg Cr were all positively correlated with poor prognosis (all P<0.01)., Conclusion: Biomarker panel may be used as a marker for early screening of patients with obstructive nephropathy and for determining poor prognosis.

Inferring new indication of approved drugs is critical not only for the elucidation of the interaction mechanisms between these drugs and their associated diseases, but also for the development of drug therapy for various human diseases. This paper proposes a network-based approach to reveal the association between 52 human diseases and potential therapeutic drugs based on multiple types of data. The advantage of the approach is that it can obtain the global relevance features for each drug-disease pair in the network by the learning local and global consistency method (LLGC). Cross-validation tests results demonstrate the proposed approach can achieve better performance comparing with previous methods. More importantly, it provides a promising strategy to maximize the value of therapeutic drugs and offer safe and effective treatments for different diseases.

Transcutaneous electrical nerve stimulation (TENS) is commonly used in clinical practice for alleviating pains and physiological disorders. It has been reported that TENS could counteract the ischemic injury happened in some vital organs. To determine the protective effect of TENS on internal organs during CH in dogs, target hypotension was maintained for 60 min at 50% of the baseline mean arterial pressure (MAP). The perfusion to the brain, liver, stomach, and kidney was recorded and apoptosis within these organs was observed. Results showed that when arriving at the target MAP, and during the maintaining stage for 10 min, perfusion to the stomach and liver in the CH+TENS group was much higher than in the CH group (P<0.05). Perfusion to the cerebral cortex greatly declined in both the controlled pressure groups when compared with the general anesthesia (GA) group (P<0.05). After withdrawing CH, the hepatic blood flow in both the CH and CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS group, were rapidly increased. By the end of MAP restoration, gastric blood flow in the CH group was still low. At 72 h after applying CH, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in stomach and kidney tissue from the CH group were significantly increased compared with those in the GA group (P<0.05). There was no significant difference in TUNEL-positive cells in the liver and hippocampus among the three groups. Our results demonstrated that CH with a 50% MAP level could cause lower perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis subsequently occurring in the stomach and kidney. TENS combined GA is able to improve the blood flow to the liver, stomach, and reduce the apoptosis in the stomach and kidney.

Objective: To examine the relationship between the HW phenotype and risk for CKD in a community population aged 40 years and older., Methods: A cross-sectional study was conducted in Zhuhai from June to October 2012. The participants were divided into three groups: Group 1, Waist circumference >90 cm in men or >85 cm in women and triglycerides ≥2 mmol/l; Group 3, Waist circumference ≤90 cm in men or ≤85 cm in women and triglycerides <2 mmol/l; Group 2, The remaining participants. The prevalence of the three subgroups and CKD were determined. The association between HW phenotype and CKD was then analyzed using SPSS (version 13.0)., Results: After adjusting for age and sex, Group 1 was associated with CKD (OR 3.08, 95% CI 2.01, 4.73, P<0.001), when compared with Group 3. Further adjustment for factors which were potential confounders and unlikely to be in the causal pathway between the HW phenotype and CKD, Group 1 was still significantly associated with CKD. The OR for CKD was 2.65 (95% CI 1.65, 4.26, P<0.001). When adjusted for diabetes and hypertension, the association of Group 1 and CKD was still significant (OR 2.09, 95% CI 1.26, 3.45, P = 0.004). Group 2 was associated with CKD (OR 1.81, 95% CI 1.29, 2.53, P = 0.001), when compared with Group 3. Further adjustment for factors which were potential confounders, Group 2 was still significantly associated with CKD. The OR for CKD was 1.75 (95% CI 1.22, 2.51, P = 0.002). When adjusted for diabetes and hypertension, the association between Group 2 and CKD still existed. The OR for CKD was 1.48 (95% CI 1.01, 2.16, P = 0.046)., Conclusion: Our results showed that HW phenotype was associated with CKD in the population aged 40 years and older.

The objective of this study is to investigate tungsten (W) contamination in soil and its enrichment in rice in the area of the world's largest and longest-operating W mines in China. Root zone soil and rice plants were sampled at 15 sites in the agricultural field adjacent to W mines and analyzed for Al, Fe, Mn, Sc, and W contents and W chemical forms in the soil samples and W contents in the rice root, stem, leaf, and grain samples. Results showed that W content in the soil ranged from 3.99 to 43.7 mg kg(-1), with more than 90% of W in the residual fraction, showing its low mobility and bioavailability. Average W contents in the rice root, stem, leaf, and grain were 7.06, 2.34, 4.76, 0.17 mg kg(-1), respectively. In addition, they were linearly independent of W content and chemical forms in the soil. Average enrichment factor values were 0.39, 0.13, 0.28, and 0.01 for the root, stem, leaf, and grain, respectively. In can be concluded that W mining activity in the Dayu county contaminated the nearby agricultural soil and led to W bioaccumulation in the rice. This may pose a health risk to residents via food and soil ingestion, which should be a focus of scrutiny.

Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1)H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

Background: Pyrrole adducts might be used as a biomarker for monitoring occupational exposure to n-hexane, but the Biological Exposure Indices of pyrrole adducts in serum and urine are still unknown. The current study was designed to investigate the biological exposure limit of pyrrole adducts for hazard assessment of n-hexane., Methods: Male Wistar rats were given daily dose of 500, 1000, 1500, 2000, 4000 mg/kg bw n-hexane by gavage for 24 weeks. The levels of pyrrole adducts in serum and urine were determined at 8, 24 hours postdose once a week. The Biological Exposure Indices was evaluated by neurological evaluation and the levels of pyrrole adducts. The difference in pyrrole adducts formation between humans and rats were estimated by using in vitro test., Results: Dose-dependent effects were observed between the doses of n-hexane and pyrrole adducts in serum and urine, and the levels of pyrrole adduct in serum and urine approached a plateau at week 4. There was a significantly negative correlation between the time to paralysis and the level of pyrrole adducts in serum and urine, while a positive correlation between gait score and levels of pyrrole adducts in serum and urine was observed. In vitro, pyrrole adducts formed in human serum was about two times more than those in rat serum at the same level of 2,5-HD., Conclusion: It was concluded that the BEIs of pyrrole adducts in humans were 23.1 ± 5.91 nmol/ml in serum 8 h postdose, 11.7 ± 2.64 nmol/ml in serum 24 h postdose, 253.8 ± 36.3 nmol/ml in urine 8 h postdose and 54.6 ± 15.42 nmol/ml in urine 24 h postdose.

Background: Urinary Kidney Injury Molecule 1 (KIM-1) is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical and population settings., Methods: Meta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves., Results: A total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%-84.0%), and specificity was 86.0% (95% CI, 74.0%-93.0%). The SROC analysis showed an area under the curve of 0.86(0.83-0.89). Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis., Limitation: Various population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation., Conclusion: Urinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.

Objectives: We sought to evaluate the feasibility and accuracy of free-breathing three-dimensional (3D) phase-sensitive inversion-recovery (PSIR) Turbo FLASH sequence for noninvasive assessment of left ventricular myocardial scar in swine models., Materials and Methods: Nine Chinese minipigs with experimentally induced acute myocardial infarction were studied. At 1 week and the study endpoint 4 weeks after myocardial infarction surgery, the 3D and 2D contrasted cardiac magnetic resonance (CMR) imaging were performed randomly by using a 1.5 T clinical MR imaging system. Comparisons of myocardial scar volume (in cubic centimeters), scar transmurality (on a 5 points scale) and image quality (on a 4 points Likert scale) were performed by using the Pearson correlation and Bland-Altman analysis (for myocardial scar volume) or κ statistics (for transmurality) or Wilcoxon signed rank test (for image quality)., Results: In 6 of the 9 pigs, all procedures were successfully completed. In these pigs, a total of 48 segments with myocardial scars were detected by both 3D and 2D sequences, and there was good agreement for classification of scar transmurality (κ=0.930). The scar volume determined by triphenyltetrazolium chloride (TTC) staining (3.52 ± 1.40 cm(3)) showed a good correlation with both 3D (3.54 ± 1.36 cm(3), r=0.957, P=0.003) and 2D sequence (3.53 ± 1.26 cm(3), r=0.942, P=0.005) at 4 weeks. And there were good correlation between scar volumes obtained from 3D and 2D techniques (r=0.859, P<0.001) at both time points. Both 3D and 2D images detected a small reduction of scar volume from week 1 to week 4 by a factor of 1.179 and 1.176, respectively. Although slightly more artifacts were observed on 2D PSIR images, the overall image quality was not significantly different between the two sequences (3.17 ± 0.83 for 2D vs. 3.25 ± 0.75 for 3D, P =0.655)., Conclusions: The free-breathing 3D PSIR Turbo FLASH sequence enables accurate assessment of left ventricular myocardial scar.

Objective: To the best of our knowledge, the association of insulin resistance (IR) with chronic kidney disease (CKD) has not been well studied in normal-weight individuals. The aim of this study is to examine whether IR is associated with CKD in non-diabetic subjects with normal weight. We also examine whether the presence of obesity modifies the association of IR with CKD., Methods: Data were drawn from a cross-sectional survey in China. Both estimated glomerular filtration rate and urinary albumin to creatinine ratio were used as markers of CKD. Logistic regression models and the quartiles of homeostatic model assessment of insulin resistance were used to explore the associations of IR with CKD in entire cohort, normal-weight and overweight/obese subpopulations., Results: In normal-weight subpopulation, the prevalence of IR and metabolic syndrome were 11.11% and 8.99%, respectively. In the entire cohort, the highest quartile HOMA-insulin resistance had a 70% increased risk for CKD (RR 1.70, 95% CI 1.07, 2.71, P=0.03, comparing the highest to the lowest quartile). However, when adding obesity to the model, the association was abolished. IR was associated with CKD in overweight/obese subpopulation but not in normal-weight subpopulation., Conclusion: IR and MetS in normal-weight individuals is common in the Chinese population. IR is associated with CKD in overweight/obese subpopulation but not in normal-weight subpopulation and the presence of obesity modifies the association of IR with CKD.

Background: Concanavalin A (ConA)-induced hepatitis is an experimental murine model mirroring the pathology of human autoimmune hepatitis., Aim: To investigate the effects of intrasplenically transplanted fetal hepatocytes (BNL.CL2) transfected with recombinant adenovirus vector expressing the IL-18 binding protein (IL-18BP) and IL-4 fusion protein on ConA-induced hepatitis in mice., Methods: Ad-IL-18BP/IL-4 was used to infect BNL.CL2 cells. IL-4 and IL-18BP fusion protein expression were detected by ELISA and Western blotting. BNL.CL2 cells infected with Ad-IL-18BP/IL-4 were intrasplenically transplanted into mice. After 10 days, mice were injected with ConA (15 mg/kg), and sacrificed 18 hours later. Liver injury was assessed by serum transaminase and liver histology. TNF-α, IL-18, IL-4, IL-10, IL-12p70 and monocyte-chemoattracting protein (MCP)-1 levels in serum and liver homogenates were detected by ELISA. Signaling molecules in liver homogenates were analyzed by Western blotting., Results: Ad-IL-18BP/IL-4 effectively expressed the IL-18BP/IL-4 fusion protein for more than 14 days in BNL.CL12 cells. Treatment of mice with Ad-IL-18BP/IL-4-BNL.CL2 before ConA injection significantly reduced the elevated plasma levels of transaminases compared with ConA control groups. TNF-α, IL-18, IL-12p70 and MCP-1 levels in serum and liver homogenates from mice transplanted with Ad-IL-18BP/IL-4-BNL.CL2 were lower and IL-4 and IL-10 levels were higher than control groups. Phosphorylation levels of NF-κB p65, AKT, p38 and JNK1/2 in liver homogenates were markedly suppressed by Ad-IL-18BP/IL-4., Conclusions: Ad-IL-18BP/IL-4 was effectively transfected into mouse BNL.CL2 cells. Intrasplenic transplantation of Ad-IL-18BP/IL-4-BNL.CL12 cells alleviated the severity of inflammation in ConA-induced experimental hepatitis and provides a useful basis for the targeted gene therapy of liver disease.

Background: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans., Results: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria., Conclusions: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors.