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Read-through chimeric RNAs are being recognized as a means to expand the functional transcriptome and contribute to cancer tumorigenesis when mis-regulated. However, current software tools often fail to predict them. We have developed RTCpredictor, utilizing a fast ripgrep tool to search for all possible exon-exon combinations of parental gene pairs. We also added exonic variants allowing searches containing common SNPs. To our knowledge, it is the first read-through chimeric RNA specific prediction method that also provides breakpoint coordinates. Compared with 10 other popular tools, RTCpredictor achieved high sensitivity on a simulated and three real datasets. In addition, RTCpredictor has less memory requirements and faster execution time, making it ideal for applying on large datasets. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse pregnancy outcomes; however, the underlying mechanisms are not fully understood. Aims: This study aimed to determine the role of exosomal miR-6891-5p in placental trophoblast dysfunction in ICP and identify new biomarkers for ICP diagnosis. Methods: Serum samples were collected from ICP patients and healthy pregnant women, and serum exosomes were extracted and identified. Fluorescent dye labeling of exosomes and cell-verified cell phagocytosis were performed. In vitro experiments were conducted by adding taurocholic acid to simulate the ICP environment. Cell proliferation and apoptosis levels were detected using flow cytometry and the cell counting kit-8 assay. Mimics were constructed to overexpress miR-6891-5p in cells, and the binding site between miR-6891-5p and YWHAE was verified using luciferase reporter genes. Results: miR-6891-5p expression was significantly decreased in serum exosomes of ICP patients. Co-culturing with exosomes derived from ICP patients' serum (ICP-Exos) decreased HTR-8/SVeno cell proliferation and increased apoptosis levels. miR-6891-5p upregulation in HTR-8/SVeno cells significantly increased cell viability and reduced cell apoptosis levels, as determined by the cell counting kit-8 assay and flow cytometry. A double luciferase assay confirmed that miR-6891-5p affected the expression of the downstream YWHAE protein. Conclusions: This study indicates that serum exosomes from ICP patients can impact the apoptosis of placental trophoblast HTR-8/SVeno cells through the miR-6891-5P/YWHAE pathway and can serve as specific molecular markers for ICP diagnosis. [ABSTRACT FROM AUTHOR]

The low detection sensitivity of lateral-flow immunochromatography assay (LFIA) based on spherical gold nanoparticle (AuNP) limits its wide applications. In the present study, AuNP dimers with strong plasma scattering and robust signal output were synthesized via the Ag ion soldering (AIS) strategy and used as labeled probes in LFIA to boost the sensitivity without any extra operation process and equipment. The established LFIA exhibited high sensitivity with a limit of detection (LOD) of 2.0 × 102 TCID50/mL for PEDV, which provides 50 times higher sensitivity than commercial LFIA based on spherical colloidal gold. In addition, the AuNP dimer–based LFIA showed strong specificity, good reproducibility, high stability, and good accordance to reverse transcription polymer chain reaction (RT-PCR) when detecting 109 clinical samples. Thus, the AuNP dimers is a promising probe for LFIA and the developed AuNP dimer–based LFIA is suitable for the rapid detection of PEDV in the field. [ABSTRACT FROM AUTHOR]

Rational tillage practice is critical for increasing soil water storage capacity and improving crop production in semiarid areas with uneven rainfall distribution. The aims of this study are to examine the effects of fallow tillage practice on wheat yield, soil water storage and water use efficiency, to investigate the appropriateness of different tillage practices under varying precipitation conditions, and to identify key factors contributing to yield variations among these practices. Here we compared the effects of different tillage practices (deep plowing, DP; subsoiling tillage, ST; and shallow rotary tillage, RT) on soil water storage and winter wheat yield in a semiarid region of the Loess Plateau in China, using field experimental data from 2009 to 2014 and APSIM (Agriculture Production System sIMulator) simulation results from 1980–2018. The APSIM well simulated the soil water storage (0–200 cm), phenology, biomass and yield of winter wheat, with R2 > 0.65 and 0.71 for each variable in calibration years and validation years, and nRMSE <16.9 % and 22.1 %, respectively, indicating a good correlation and medium consistency between simulated and measured values. The simulated average annual soil water storage, biomass, yield, and water use efficiency under DP were 8.4 %, 18.4 %, 25.5 %, and 22.3 % higher than under RT, and 7.9 %, 13.8 %, 22.4 %, and 21.4 % higher than under ST, respectively. These variables did not differ between ST and RT treatments. Compared to RT, DP improved the soil water storage by 9.0 %–12.0 % from October to March, increased by 4.8 %–7.1 % during the fallow period, and increased by 2.5 %–7.4 % from April to June. This was mainly because DP had more precipitation reserves during the fallow period, but in the later stage of wheat growth, as precipitation increased, the difference in soil water storage between different tillage practices decreased. Wheat yield, precipitation and soil water storage were significantly and positively correlated. The difference in yield between DP and RT was greater at the medium than at low and high yield production levels, but that between ST and RT was not significant. DP increased soil water storage from October to March and improved wheat yield, which should be recommended to ensure high wheat yield and efficient water use in the Loess Plateau. This study validated the applicability of DP tillage in semi-arid areas on a long-term scale and found its superiority at different yield production levels. • Deep plowing (DP) had higher wheat yield than shallow rotary (RT) and subsoiling tillage (ST). • DP improved water use efficiency and soil water storage especially from October to March. • Wheat yield, precipitation and soil water storage were significantly and positively correlated. • Yield difference between DP and RT was greater at medium than at low and high yield levels. [ABSTRACT FROM AUTHOR]

Background: To evaluate the relationship between atherosclerosis and Alzheimer's disease (AD), we conducted a systematic review and meta‐analysis to study the difference of carotid intima–media thickness (CIMT) and the prevalence of atherosclerosis between AD patients and non‐AD controls. Methods: The studies on the association between atherosclerosis and AD were manually searched in PubMed, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) spanned to September 2018 according to PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. Results: Thirteen studies were included in the final analysis, seven studies with data on the mean CIMT (610 cases and 417 controls) and ten studies reporting on the prevalence of atherosclerosis (1,698 cases and 6,452 controls). Compared with controls, AD group showed a significantly higher CIMT (overall standard mean difference = 0.94; 95% CI, 0.48–1.40; p <.0001) and an increased prevalence of atherosclerosis (OR = 1.46; 95% CI, 1.26–1.68; p <.0001). Conclusions: Atherosclerosis is significantly associated with AD. CIMT might be a useful marker to predict the risk of AD and assess the vascular burden. The finding is also important for possible prevention and treatment of AD in the future. [ABSTRACT FROM AUTHOR]

Clinical statistics show that women and men act differently in various diseases. In the recent coronavirus disease 2019 (COVID-19) pandemic, scientists reported that men suffered more severe symptoms and higher mortality than women. Chimeric RNA, as a new layer of RNA diversification, is defined as a hybrid transcript containing exons from two originally separate genes. To understand the fundament of sex-biased COVID-19 phenotypes, we aim to discover sex-specific chimeric RNAs and their potential functions. Here, we identified a female-specific chimeric transcript U-C by analyzing 7,059 RNA-seq datasets of the Genotype-Tissue Expression (GTEx) Project. This chimeric transcript was validated to be specific to females and enriched in circulating blood cells. In contrast, the parental genes are expressed in both males and females. We then detected differential expression of U-C in 90 female COVID patients from the Tongji Hospital in China. U-C expression was detected at a baseline range in all asymptomatic patients while significantly decreased in patients with severe symptoms. It has been reported that female COVID patients had fewer circulating neutrophils and monocytes. We then investigated the potential function of U-C during in vitro myeloid differentiation. A larger population of CD11b+ myeloid cells was observed after knocking down U-C specifically. Furthermore, we investigated the mechanism of this chimeric transcript formation. U-C was found to be a product of cis-splicing between two X-linked neighboring genes and expressed exclusively from the inactive X chromosome, which is mediated by an intergenic chromatin loop formed between the U-C junction sites. [ABSTRACT FROM AUTHOR]

• Determination of ABM, IVM, ABZ and its metabolites in meat by HPLC-PDA. • This method shows a reduced detection time and can be used with more targets. • The process of the chromatography conditions is optimized. Antimicrobial drugs are frequently used in a combination or shuttle way to cope with coinfection of bacteria or parasites and prevent drug resistance, thus the accurate quantification of multiple drug residues in animal-derived foods is crucial to ensure food safety. Here, a simple and efficient high-performance liquid chromatography-photodiode array (HPLC-PDA) method was established for the simultaneous quantitative screening of six common residues of antiparasitic drugs, including abamectin (ABM), ivermectin (IVM), albendazole (ABZ) and the three metabolites of ABZ in beef and chicken. The LODs and LOQs for six target compounds in beef and chicken are determined to be 3.2 to 12.5 µg/kg and 9.0 to 30.0 µg/kg, respectively. The calibration curves show good linearity (R2 ≥ 0.9990) between the peak area and concentration. The recoveries from the fortified blank samples are all above 85.10%. Finally, the applicability of the HPLC-PDA method is successfully demonstrated by the real sample analysis. [ABSTRACT FROM AUTHOR]

Inhibin subunit beta A (INHBA) is a member of the transforming growth factor-beta (TGF-β) superfamily that plays a fundamental role in various cancers. However, a systematic analysis of the exact role of INHBA in patients with gastric cancer (GC) has not yet been conducted. We evaluated the expression levels of INHBA and the correlation between INHBA and GC prognosis in GC. The relationship between INHBA expression, immune infiltration levels, and type markers of immune cells in GC was also explored. In addition, we studied INHBA mutations, promoter methylation, and functional enrichment analysis. Besides, high expression levels of INHBA in GC were significantly related to unfavorable prognosis. INHBA was negatively correlated with B cell infiltration, but positively correlated with macrophage and most anticancer immunity steps. INHBA expression was positively correlated with the type markers of CD8+ T cells, neutrophils, macrophages, and dendritic cells. INHBA has a weak significant methylation level change between tumor and normal tissues and mainly enriched in cancer-related signaling pathways. The present study implies that INHBA may serve as a potential biomarker for predicting the prognosis of patients with GC. INHBA is a promising predictor of immunotherapy response, with higher levels of INHBA indicating greater sensitivity. [ABSTRACT FROM AUTHOR]

[Display omitted] • The WHCNS model performed well in simulating NH 3 flux measured by a continuous ventilation method. • Urea split application reduced the peak of NH 3 flux but increased total NH 3 loss. • Controlled-release urea application significantly reduced NH 3 loss compared to urea. • The controlled-release urea rate was recommended to reduce N loss without reducing yield. Ammonia volatilization, a main pathway of nitrogen (N) loss in paddy fields, can easily lead to environmental problems, such as haze and water eutrophication. Field measurement of ammonia volatilization is time-consuming and expensive. Soil–crop system models can simulate the effect of different fertilizer management practices on NH 3 volatilization and compensate for the limitations of field measurement. Therefore, the WHCNS (soil Water Heat Carbon Nitrogen Simulator) model was used to evaluate the feasibility of simulating NH 3 volatilization in paddy fields under different N fertilizer types and application methods. The field experiment, including four treatments of farmer's practice (FP), basal application of urea in one dose (SBN), split application of urea in three doses (SPN), and basal application of controlled-release urea in one dose (CRU), was conducted from 2013 to 2014. All treatments were conducted with a fertilizer rate of 165 kg N ha−1, except for FP with a rate of 210 kg N ha−1. The measured dry matter weight, grain yield, N uptake, and NH 3 flux were used to test the WHCNS model. The model evaluation indices of Nash–Sutcliffe efficiency (NSE) and index of agreement (d) were close to 1 for the measured variables, except for NSE of yield (0.16). The normalized root mean square error (NRMSE) of NH 3 flux was slightly over 30%, but lower than 30% for the other items. Results showed that the model can successfully simulate rice yield and NH 3 flux of urea and controlled-release urea under different application methods. The simulated annual average cumulative NH 3 losses of FP, SBN, SPN, and CRU accounted for 18.9%, 17.8%, 20.6%, and 10.1% of their N inputs, respectively. Compared with the FP treatment, the ratios of NH 3 losses of the SBN and CRU treatments were decreased by 1.2%-8.8%. Compared with the SBN treatment (the same rate of 165 kg N ha−1), SPN reduced the peak of NH 3 flux but increased the cumulated NH 3 losses and CRU significantly reduced the NH 3 flux and cumulative NH 3 losses. The application rate of controlled-release urea could be further optimized by refined model calculations to reduce NH 3 volatilization and total N loss while maintaining yield. [ABSTRACT FROM AUTHOR]

ABSTRACT Both elevated atmospheric CO2 concentration ([CO2]) and increased temperature exert notable influences on wheat (Triticum aestivum L.) growth and productivity when examined individually. Nevertheless, limited research comprehensively investigates the combined effects of both factors. Winter wheat was grown in environment‐controlled chambers under two concentrations of CO2 (ambient CO2 concentration and ambient CO2 concentration plus 200 µmol mol−1) and two levels of temperature (ambient temperature and ambient temperature plus 2°C). The phenology, photosynthesis, carbohydrate and nitrogen metabolism, yield and quality responses of wheat were investigated. Elevated [CO2] did not counteract warming‐induced shortening of wheat phenological period but prolonged grain filling. Even though photosynthetic adaptation occurred during the reproductive growth period, elevated [CO2] still significantly enhanced carbohydrate accumulation under warming, particularly at the grain filling stage, thereby increasing yield by 20.1% compared with the ambient control. However, elevated [CO2] inhibited nitrogen assimilation at the grain filling stage under increased temperature by downregulating the expression levels of TaNR, TaNIR, TaGS1 and TaGOGAT and reducing glutamine synthetase activity, which directly led to a significant decrease of 19.4% in grain protein content relative to the ambient control. These findings suggest that elevated [CO2] will likely increase yield but decrease grain nutritional quality for wheat under future global warming scenarios. [ABSTRACT FROM AUTHOR]

Methanol to aromatic reaction is an alternative pathway to produce aromatics from non‐petroleum resources. Zn‐modified ZSM‐5 zeolite is the widespread catalyst for MTA due to its high activity and selectivity to aromatics. However, a desired high yield of aromatics is usually accompanied with undesired coke formation and fast deactivation of catalyst, because aromatic molecules also serve as the precursor for coke formation. To decouple the aromatic yield and coke formation rate, in this work we use Zn‐ZSM‐5 to investigate coke formation and catalyst deactivation. The coke distribution along the catalyst bed was analyzed and its correlation with the concentration gradient of methanol, olefins and aromatics along the bed was deciphered. Coke was found to form very fast at catalyst bed in the copresence of methanol and aromatics. On the contrary, much less coke was observed at the later layers of the catalyst bed where methanol had been fully converted and aromatics were present in the highest concentration. Based on this finding, we adjusted the reaction conditions to successfully improve the yield of aromatics without reducing catalyst lifetime in compromise, by applying a higher methanol partial pressure that enables a faster consumption of methanol and reduces the period of copresence of methanol and aromatics. [ABSTRACT FROM AUTHOR]

Background: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. Methods: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. Results: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. Conclusion: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. Trial registration: ClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19. [ABSTRACT FROM AUTHOR]

• WHCNS model performed well for simulating maize growth, water and N dynamics in desert oasis. • Increasing the irrigation times can reduce N leaching and improve N use efficiency without reducing yield. • Best management practices were developed under different initial soil mineral N (ISMN) levels. • The optimal N application rate decreased linearly with increase of ISMN when ISMN was <384 kg ha−1. Determining the best management practices (BMPs) under different initial soil mineral N (ISMN) levels is helpful to improve water and N use efficiencies (WUE, NUE) and protect the environment. In this study, a two-year field experiment of spring maize was conducted from 2014 to 2015 in northwest China. Five treatments were designed, including one local farmer practice (I 480-4 N 280 , 280 kg N ha−1 fertilizer and irrigated 480 mm with four irrigation events) and four conservation treatments (I 420-4 N 200 , I 420-5 N 200 , I 420-6 N 200 and I 420-7 N 200 , standing for 200 kg N ha−1 fertilizer and irrigated 420 mm with four to seven irrigation events, respectively). Measured yield, leaf area index, soil water content and soil nitrate concentration were used to evaluate a soil-crop model (WHCNS, soil Water Heat Carbon Nitrogen Simulator), which was then used to simulate the effects of water and N management practices on water consumption, N fates, and crop growth. Then, the integrated index considering the agronomic, economic, and environmental impacts was simulated using 35,100 combinations of irrigation and fertilizer N scenarios, which were designed to develop BMPs under different ISMN levels (ranging from 0 to 625 kg N ha-1 in a 1.8 m-soil profile) and seasons of weather data (from 2001 to 2015). Results showed I 420-5 N 200 was the best with a high yield, WUE and NUE, and low N loss among five treatments. The optimal irrigation amount (ranging from 350−600 mm) was related to precipitation amount. The optimal N rate decreased linearly with the increase of ISMN when ISMN was <384 kg ha−1, and reached a plateau (0 kg N ha−1) when ISMN was >384 kg ha−1. In this study, we developed a simple linear model to determine the best N application rates under different ISMNs. This method is important to help farmers achieve multiple goals of high yield, resource conservation and reduced environmental impacts simultaneously. [ABSTRACT FROM AUTHOR]

• The WHCNS model performed well in simulating rice growth, water and N fates. • Ammonia volatilization and N runoff exponentially increased with N fertilizer rate. • Ammonia volatilization and denitrification accounted for 72% of the total N loss. • Reducing the total N rate and increasing topdressing rate can effectively reduce N loss. • The optimal N management was recommended to reduce negative environmental impacts. Excessive fertilization in rice paddy fields leads to surface water eutrophication, groundwater contamination and air pollution. Determining optimum nitrogen (N) management is essential for maintaining rice yield while reducing the environmental risk caused by N loss. A two-year field experiment (2017–2018) was carried out in a typical paddy field in the middle reaches of the Yangtze River. The WHCNS (soil Water Heat Carbon Nitrogen Simulator) model was calibrated and evaluated for simulations of measured ponding water depth, evapotranspiration, aboveground dry matter, yield, runoff and crop N. The model was then used to evaluate the effects of different N fertilizer rates and split-N application ratios (SNR) practices on crop growth and N losses. Results showed that the model performed well in simulating rice growth and N losses in the region. Ammonia volatilization and denitrification were the mainly pathways of N loss in paddy field, and their two-year average losses were 34% and 38% of the total N loss, respectively. N leaching accounted for 23%, and runoff N loss accounted for 5% of total N loss. N losses were evaluated for two different scenarios and simulated ratios of ammonia volatilization, denitrification, N leaching, and runoff to total N loss under different N management scenarios were 15%–53%, 33%–55%, 6%–30%, and 4%–8%, respectively. Ammonia volatilization and N runoff exponentially increased with an increase of N fertilizer rate, whereas denitrification and N leaching showed an increasing and then a decreasing trend. Yield increased by 36 kg ha−1, and the total N loss decreased by 32.6 kg N ha−1 when the N fertilizer rate was reduced from 231 kg N ha−1 to 155 kg N ha−1 and the SNR was changed from 5:3:1 to 1:1:4. Therefore, reducing the N fertilizer rate and increasing the SNR in the late rice growing season can significantly reduce N loss and effectively improve N use efficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] • A SERS immunochromatography was developed for the detection of S. enteritidis. • Au-core and Ag-shell sandwiched with 4-MBA nanoparticles was used as labels. • Qualitative and quantitative detection can be completed in 20 min. • The sensitivity is high with a LOD of 1.36 × 102 CFU mL−1. Salmonella enteritidis (S. enteritidis) is a common zoonotic pathogen which can cause acute gastroenteritis characterized with fever, diarrhea and vomiting, posing a serious threat to public health. Rapid and accurate detection of S. enteritidis is in great demand for food safety and timely diseases treatment. In the present study, a surface-enhanced Raman scattering lateral flow immunoassay sensor (SERS-LFIA) was developed for the rapid, ultrasensitive and quantitative detection of S. enteritidis using Au-core Ag-shell nanoparticles sandwiched with Raman molecules. S. enteritidis could be quantitatively detected by SERS-LFIA at concentrations ranging from 1 × 103 to 1 × 107 CFU mL−1, with limits of detection (LOD) of 1 × 105 CFU mL−1 and 1.36 × 102 CFU mL−1 based on naked eye observation and SERS signal analysis, respectively. No cross-reaction was observed from other serotypes of Salmonella and other common pathogens. The coefficient of variation for both the intra- and inter-batch repetitive tests were less than 10%. The recovery rates of spiking feces and eggshells were between 94.8% and 104.7%. Thus, this SERS-LFIA is able to quantitatively detect S. enteritidis in 20 min with high sensitivity, specificity, repeatability, and could be a promising method for the early detection of S. enteritidis in various clinical samples. [ABSTRACT FROM AUTHOR]

Pathway analyses are playing an increasingly important role in understanding biological mechanism, cellular function and disease states. Current pathway-identification methods generally focus on only the changes of gene expression levels; however, the biological relationships among genes are also the fundamental components of pathways, and the dysregulated relationships may also alter the pathway activities. We propose a powerful computational method, Edge Set Enrichment Analysis (ESEA), for the identification of dysregulated pathways. This provides a novel way of pathway analysis by investigating the changes of biological relationships of pathways in the context of gene expression data. Simulation studies illustrate the power and performance of ESEA under various simulated conditions. Using real datasets from p53 mutation, Type 2 diabetes and lung cancer, we validate effectiveness of ESEA in identifying dysregulated pathways. We further compare our results with five other pathway enrichment analysis methods. With these analyses, we show that ESEA is able to help uncover dysregulated biological pathways underlying complex traits and human diseases via specific use of the dysregulated biological relationships. We develop a freely available R-based tool of ESEA. Currently, ESEA can support pathway analysis of the seven public databases (KEGG; Reactome; Biocarta; NCI; SPIKE; HumanCyc; Panther). [ABSTRACT FROM AUTHOR]

Aims: N2O emitted by agricultural ecosystems has a great impact on global warming and climate change. The use of controlled-release fertilizers (CRF) can decrease greenhouse gas emissions. However, the general patterns and variability of nitrogen functional genes in response to CRF associated with N2O emission have not been synthesized under climate change. Methods: We investigated the effects of CRF, elevated CO2 concentration (EC), elevated temperature (ET), and their combination on N2O emission, enzyme activities and gene abundances. Results: We found that the cumulative N2O emissions was in the range of 0.39–1.65 kg·ha−1 in the wheat-growing season, accounting for 0.54%–2.29% of the total nitrogen input. N2O emissions were considerably positively correlated with ammonia-oxidizing bacteria (AOB) at elongation stage. CRF inputs significantly decreased N2O emissions by 29 − 66% compared with urea due to decreased AOB abundance and inhibited nitrite reductase activities at elongation stage. EC significantly decreased N2O emissions by 30 − 50% likely resulting from the inhibition in nitrifying and denitrifying community compared with ambient CO2 concentration. ET significantly increased N2O emissions by increasing N mineralization in wheat soil under CRF due to higher NH4+-N and NO3−-N concentration in wheat soil at elongation stage. In addition, ECET had antagonistic effect on N2O emissions. CRF had no significant effect on wheat yield under climate change scenarios. Conclusions: CRF decreased the cumulative N2O emissions under climate change scenarios. This is critical for understanding the responses of N2O emissions from wheat soil under CRF to future CO2 enrichment and warming for the establishment of mitigation and adaptation policies. [ABSTRACT FROM AUTHOR]

To investigate the effects of nitrification inhibitors applied in the wheat season on the soil inorganic nitrogen (N), N2O emissions and related enzyme activities in the soybean season for the wheat-soybean rotation system under the background of climate change, different atmospheric CO2 concentration (400 and 600 µmol/mol) and air temperature (ambient temperature T and T+2 °C) were set in the control air chamber. The contents of soybean soil nitrate and ammonium N, nitrification and denitrification-related enzyme activities and N2O emissions were measured when nitrification inhibitors were added in the wheat season. The results showed that the addition of nitrification inhibitor combined with wheat straw returning to the field in wheat season increased soil nitrate N and ammonium N in soybean season, whereas it had little effect on the enzyme activities of soil nitrification-denitrification. Elevated air temperature (ET) significantly increased the content of nitrate N in soybean soil, while the content of ammonium N significantly decreased. At the conditions of increased atmospheric CO2 concentration (EC) or simultaneously increased air temperature and CO2 concentration (ECT), soil nitrate N and ammonium N content both increased, whereas there were no significantly difference with the inorganic N content under ambient temperature and CO2 concentration (CK). The enzyme activities of soil nitrification-denitrification under different environmental conditions showed no obvious regularity. Under ET and ECT conditions, the total amount of N2O emission in soybean growing season was significantly higher than that in CK treatment, and the addition of nitrification inhibitors reduced N2O emission. The difference of N2O emissions between EC and CK conditions was small, whereas the N2O emission of nitrification inhibitor treatment was significantly higher than that of common urea treatment under CK condition. To sum up, under the background of rising air temperature and CO2 concentration in the future, reasonable application of nitrification inhibitors is beneficial to the increase of available N in soybean soil, whereas the increase of air temperature (ET and ECT) may increase N2O emissions, and adding nitrification inhibitors can reduce N2O emissions. The changes in N2O emissions are not obvious when the CO2 concentration (EC) increased alone. This study can provide a theoretical support for fertilization management and farmland N2O emission reduction under the wheat- soybean crop rotation system under the background of future climate change. [ABSTRACT FROM AUTHOR]

Aims: Elevated atmospheric [CO2] generally increases wheat growth and biomass by improving photosynthesis. These increase cause greater N uptake by plants from soil, which may affect soil properties and microbial communities. Nitrification inhibitor is useful tool to inhibit the nitrification process and effectively slow down nitrogen (N) losses. However, it remains unclear how the addition of nitrification inhibitor under elevated [CO2] will affect the soil microbial community and function.We investigated the changes in soil properties, microbial community and function by using a metagenomic technique in soil fertilized with urea (C) with or without nitrification inhibitor (NI) under ambient [CO2] or elevated [CO2] (+ 200 μmol mol–1 above ambient [CO2])A large number of microbial genes related to carbon (C) fixation and phosphorus (P) release were increased by elevated [CO2], but those related to C degradation were decreased. Elevated [CO2] decreased soil ammonium (NH4+) (-46.23%) and nitrate (NO3−) (− 5.35%), and shifted the microbial community towards oligotrophic microorganisms due to soil N limitations. The addition of nitrification inhibitor under elevated [CO2] decreased the ammonium-oxidizing amoA gene abundance to keep soil N stable for longer, and promoted soil C and P cycle compared with elevated [CO2] alone.The overall changes in microbial communities and soil N pools induced by nitrification inhibitor under elevated [CO2] kept soil N stable, and promoted soil biogeochemical cycle, thereby increasing the potential growth rate of the microbial community.Methods: Elevated atmospheric [CO2] generally increases wheat growth and biomass by improving photosynthesis. These increase cause greater N uptake by plants from soil, which may affect soil properties and microbial communities. Nitrification inhibitor is useful tool to inhibit the nitrification process and effectively slow down nitrogen (N) losses. However, it remains unclear how the addition of nitrification inhibitor under elevated [CO2] will affect the soil microbial community and function.We investigated the changes in soil properties, microbial community and function by using a metagenomic technique in soil fertilized with urea (C) with or without nitrification inhibitor (NI) under ambient [CO2] or elevated [CO2] (+ 200 μmol mol–1 above ambient [CO2])A large number of microbial genes related to carbon (C) fixation and phosphorus (P) release were increased by elevated [CO2], but those related to C degradation were decreased. Elevated [CO2] decreased soil ammonium (NH4+) (-46.23%) and nitrate (NO3−) (− 5.35%), and shifted the microbial community towards oligotrophic microorganisms due to soil N limitations. The addition of nitrification inhibitor under elevated [CO2] decreased the ammonium-oxidizing amoA gene abundance to keep soil N stable for longer, and promoted soil C and P cycle compared with elevated [CO2] alone.The overall changes in microbial communities and soil N pools induced by nitrification inhibitor under elevated [CO2] kept soil N stable, and promoted soil biogeochemical cycle, thereby increasing the potential growth rate of the microbial community.Results: Elevated atmospheric [CO2] generally increases wheat growth and biomass by improving photosynthesis. These increase cause greater N uptake by plants from soil, which may affect soil properties and microbial communities. Nitrification inhibitor is useful tool to inhibit the nitrification process and effectively slow down nitrogen (N) losses. However, it remains unclear how the addition of nitrification inhibitor under elevated [CO2] will affect the soil microbial community and function.We investigated the changes in soil properties, microbial community and function by using a metagenomic technique in soil fertilized with urea (C) with or without nitrification inhibitor (NI) under ambient [CO2] or elevated [CO2] (+ 200 μmol mol–1 above ambient [CO2])A large number of microbial genes related to carbon (C) fixation and phosphorus (P) release were increased by elevated [CO2], but those related to C degradation were decreased. Elevated [CO2] decreased soil ammonium (NH4+) (-46.23%) and nitrate (NO3−) (− 5.35%), and shifted the microbial community towards oligotrophic microorganisms due to soil N limitations. The addition of nitrification inhibitor under elevated [CO2] decreased the ammonium-oxidizing amoA gene abundance to keep soil N stable for longer, and promoted soil C and P cycle compared with elevated [CO2] alone.The overall changes in microbial communities and soil N pools induced by nitrification inhibitor under elevated [CO2] kept soil N stable, and promoted soil biogeochemical cycle, thereby increasing the potential growth rate of the microbial community.Conclusions: Elevated atmospheric [CO2] generally increases wheat growth and biomass by improving photosynthesis. These increase cause greater N uptake by plants from soil, which may affect soil properties and microbial communities. Nitrification inhibitor is useful tool to inhibit the nitrification process and effectively slow down nitrogen (N) losses. However, it remains unclear how the addition of nitrification inhibitor under elevated [CO2] will affect the soil microbial community and function.We investigated the changes in soil properties, microbial community and function by using a metagenomic technique in soil fertilized with urea (C) with or without nitrification inhibitor (NI) under ambient [CO2] or elevated [CO2] (+ 200 μmol mol–1 above ambient [CO2])A large number of microbial genes related to carbon (C) fixation and phosphorus (P) release were increased by elevated [CO2], but those related to C degradation were decreased. Elevated [CO2] decreased soil ammonium (NH4+) (-46.23%) and nitrate (NO3−) (− 5.35%), and shifted the microbial community towards oligotrophic microorganisms due to soil N limitations. The addition of nitrification inhibitor under elevated [CO2] decreased the ammonium-oxidizing amoA gene abundance to keep soil N stable for longer, and promoted soil C and P cycle compared with elevated [CO2] alone.The overall changes in microbial communities and soil N pools induced by nitrification inhibitor under elevated [CO2] kept soil N stable, and promoted soil biogeochemical cycle, thereby increasing the potential growth rate of the microbial community. [ABSTRACT FROM AUTHOR]

Nitrogen (N) fertilizer input will likely increase to meet the food demands of a growing population under climate change conditions, characterized by increasing atmospheric CO 2 concentration and temperature. Nitrification inhibitors have the potential to reduce N 2 O emissions from N fertilized croplands. However, it remains unclear whether future climate change scenarios could affect the effectiveness of nitrification inhibitors. In a two-year study, winter wheat (Triticum aestivum L.) was cultivated in climate-controlled growth chambers with an elevated CO 2 concentration (ambient +200 μmol mol−1) and increased temperature (ambient +2 °C). Urea was applied with or without nitrapyrin (0.5 % of urea-N). In this study, we measured nitrous oxide (N 2 O) fluxes, soil ammonium and nitrate levels, and the abundance of five nitrogen-cycling genes related to nitrification (amo A of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA)) and denitrification (nir S, nir K and nos Z). Key findings included the following: 1) without nitrapyrin, cumulative N 2 O emissions were not significantly altered by increased temperature, but decreased 24.9 % by the combination of elevated CO 2 and temperature treatment and 17.5 % by the elevated CO 2 alone. NO 3 −-N accumulation occurred in soils under increased CO 2 and temperature, both individual and in combination; 2) nitrapyrin effectively reduced AOB abundance, inhibiting NO 3 −-N accumulation and N 2 O emission, irrespective of CO 2 concentrations and temperature. However, under the combination of elevated CO 2 and temperature conditions, the efficiency of nitrapyrin in reducing N 2 O emission was lower (−13 % to −49 %) than that in the control (−28 % to −65 %) and elevated CO 2 (−32 % to −71 %) conditions. This reduced effectiveness of the combined treatment can be attributed to the inability of nitrapyrin to inhibit the AOA, nir S and nir K genes. Thus, nitrapyrin is expected to reduce N 2 O emissions under future climate change scenarios, but the efficacy may be lower than previously expected when CO 2 concentration and temperature increase simultaneously. The indirect effects of nitrapyrin on denitrifiers under climate change scenarios should be considered in future research. The N 2 O emission reduction effect of nitrification inhibitors will be weakened under future climate change scenarios. [Display omitted] • Elevated CO 2 (e CO 2) and warming decreased N 2 O emission in this wheat system. • Nitrapyrin was less effective in N 2 O inhibition under e CO 2 and warming. • AOB was sensitive to nitrapyrin under all climate change treatments. • AOA, nir K and nir S affected the efficiency of nitrapyrin under e CO 2 and warming. [ABSTRACT FROM AUTHOR]

Purpose: Specific gene fusions and their fusion products (chimeric RNA and protein) have served as ideal diagnostic markers and therapeutic targets for cancer. However, few systematic studies for chimeric RNAs have been conducted in neuroendocrine prostate cancer (NEPC). In this study, we explored the landscape of chimeric RNAs in different types of prostate cancer (PCa) cell lines and aimed to identify chimeric RNAs specifically expressed in NEPC. Methods: To do so, we employed the RNA-seq data of eight prostate related cell lines from Cancer Cell Line Encyclopedia (CCLE) for chimeric RNA identification. Multiple filtering criteria were used and the candidate chimeric RNAs were characterized at multiple levels and from various angles. We then performed experimental validation on all 80 candidates, and focused on the ones that are specific to NEPC. Lastly, we studied the clinical relevance and effect of one chimera in neuroendocrine process. Results: Out of 80 candidates, 15 were confirmed to be expressed preferentially in NEPC lines. Among them, 13 of the 15 were found to be specifically expressed in NEPC, and four were further validated in another NEPC cell line. Importantly, in silico analysis showed that tumor malignancy may be correlated to the level of these chimeric RNAs. Clinically, the expression of TMPRSS2-ERG (e2e4) was elevated in tumor tissues and indicated poor clinical prognosis, whereas the parental wild type transcripts had no such association. Furthermore, compared to the most frequently detected TMPRSS2-ERG form (e1e4), e2e4 encodes 31 more amino acids and accelerated neuroendocrine process of prostate cancer. Conclusions: In summary, these findings painted the landscape of chimeric RNA in NEPC and supported the idea that some chimeric RNAs may represent additional biomarkers and/or treatment targets independent of parental gene transcripts. [ABSTRACT FROM AUTHOR]

Background: Amnestic mild cognitive impairment (aMCI) is often the prodromal stage of Alzheimer's disease (AD). Although previous studies have suggested that computerized cognitive training is an effective non-pharmacological intervention for aMCI, large-sample, randomized controlled studies are warranted to provide a high level of evidence.Objective: To identify the efficacy of computerized cognitive training for aMCI.Methods: This study will include 260 patients diagnosed with aMCI from 8 centers in China. A computerized multi-domain adaptive training program will be used in this study, and the targeted cognitive domains include memory, attention, language, and executive function. The patients will be randomized into either a cognitive-training group or an active-control group. The intervention is a 12-week internet-based cognitive training performed for 40 minutes per day, 4 days a week. Neuropsychological assessments and structural and functional MRI will be obtained at baseline, at the end of the intervention, and 6 months after randomization. The primary outcome will be the global cognitive function score assessed by Montreal Cognitive Assessment. The secondary outcomes include changes in other neuropsychological assessments and neuroplasticity changes measured by structural and functional MRI.Results: The trial is currently ongoing, and it is anticipated that recruitment will be completed in December 2020.Conclusion: This multi-center, large-sample, randomized controlled trial will investigate the short and long-term effects of computerized cognitive training in patients with aMCI. Furthermore, the combination of functional and structural MRI results will also reveal the underlying mechanisms of the effect of intervention. [ABSTRACT FROM AUTHOR]

In order to obtain the effective antidiabetic polysaccharide derivative, a selenylated polysaccharide (Se-MCPIIa-1), with an average molecular weight (MW) of 4.0038 × 104 Da, was synthesized by reduction of sodium selenite with ascorbic acid in the presence of Momordica polysaccharides (MCPIIa). The selenium (Se) content of Se-MCPIIa-1 was up to 445.0 μg/g, and its average diameter of monodisperse spherical particle size was around 63.78 nm. The morphology and physicochemical properties of Se-MCPIIa-1 were characterized by scanning electron microscope (SEM), atomic force microscope (AFM), Fourier transform infrared spectrometry (FT-IR) and Raman spectroscopy, respectively. The results indicated that Se was conjunct with MCPIIa by esterification. Moreover, the oral administration of Se-MCPIIa-1 showed a gradual normalization in the levels of hypoglyemic test in the STZ-induced diabetic mice. The anti-diabetic effects of Se-MCPIIa-1 in vivo showed that Se-MCPIIa-1 can significantly reduce fasting blood glucose levels and enhance insulin levels as well as antioxidant enzyme activities in diabetic mice with an optimal dosage of 20 mg/kg/body weight. In addition, it was found from histopathological data that Se-MCPIIa-1 could prevent pancreatic islets, liver and kidney damage from diabetes, which suggested that Se-MCPIIa-1 is a promising novel Se supplement and could be applied in the field of food and medicine. Unlabelled Image • A novel selenium-bound polysaccharide Se-MCPIIa-1 was synthesized by selenylation modification. • The physicochemical properties and morphological were investigated by spectroscopy techniques. • Selenylation of polysaccharides, Se-MCPIIa-1 increased hypoglycemic activity. [ABSTRACT FROM AUTHOR]

The atmospheric [CO 2 ] and the frequency and intensity of extreme weather events such as drought are increased, leading to uncertainty to soybean production. Elevated [CO 2 ] (e CO 2) partially mitigates the adverse effects of drought stress on crop growth and photosynthetic performance, but the mitigative mechanism is not well understood. In this study, soybean seedlings under drought stress simulated by PEG-6000 were grown in climate chambers with different [CO 2 ] (400 μmol mol−1 and 700 μmol mol−1). The changes in anatomical structure, wax content, photosynthesis, and antioxidant enzyme were investigated by the analysis of physiology and transcriptome sequencing (RNA-seq). The results showed that e CO 2 increased the thickness of mesophyll cells and decreased the thickness of epidermal cells accompanied by reduced stomatal conductance, thus reducing water loss in soybean grown under drought stress. Meanwhile, e CO 2 up-regulated genes related to wax anabolism, thus producing more epidermal wax. Under drought stress, e CO 2 increased net photosynthetic rate (P N), ribulose-1,5-bisphosphate carboxylase/oxygenase activity, and alerted the gene expressions in photosynthesis. The increased sucrose synthesis and decreased sucrose decomposition contributed to the progressive increase in the soluble saccharide contents under drought stress with or without e CO 2. In addition, e CO 2 increased the expressions of genes associated with peroxidase (POD) and proline (Pro), thus enhancing POD activity and Pro content and improving the drought resistance in soybean. Taken together, these findings deepen our understanding of the effects of e CO 2 on alleviating drought stress in soybean and provide potential target genes for the genetic improvement of drought tolerance in soybean. • e CO 2 altered the thickness of mesophyll and epidermis cells, thus improving WUE. • e CO 2 up-regulated genes related to wax anabolism, thus producing more epidermal wax. • e CO 2 increased sucrose synthesis and P N , thus enhancing carbon assimilation. • e CO 2 promoted the gene expressions involved in POD, Pro, and photosynthesis. • e CO 2 mitigated the adverse effects of drought stress on soybean. [ABSTRACT FROM AUTHOR]

The continuous accumulation of Cd has long-lasting detrimental effects on plant growth and food safety. Although elevated CO 2 concentration (EC) has been reported to reduce Cd accumulation and toxicity in plants, evidence on the functions of elevated CO 2 concentration and its mechanisms in the possible alleviation of Cd toxicity in soybean are limited. Here, we used physiological and biochemical methods together with transcriptomic comparison to explore the effects of EC on Cd-stressed soybean. Under Cd stress, EC significantly increased the weight of roots and leaves, promoted the accumulations of proline, soluble sugars, and flavonoid. In addition, the enhancement of GSH activity and GST gene expressions promoted Cd detoxification. These defensive mechanisms reduced the contents of Cd2+, MDA, and H 2 O 2 in soybean leaves. The up-regulation of genes encoding phytochelatin synthase, MTPs, NRAMP, and vacuoles protein storage might play vital roles in the transportation and compartmentalization process of Cd. The MAPK and some transcription factors such as bHLH, AP2/ERF, and WRKY showed changed expressions and might be engaged in mediation of stress response. These findings provide a boarder view on the regulatory mechanism of EC on Cd stress and provide numerous potential target genes for future engineering of Cd-tolerant cultivars in soybean breeding programs under climate changes scenarios. [Display omitted] • e CO 2 attenuated Cd accumulation and growth inhibition in soybean under Cd stress. • e CO 2 enhanced osmoprotective and antioxidant systems in Cd-stressed plants. • e CO 2 induced increase in GST expression and GSH activity might enhance Cd tolerance. • e CO 2 enhanced the expression of genes engaged in Cd transportation and distribution. • e CO 2 modulated expression of genes associated with MAPK, bHLH, WRKY, ERF, and MYB. [ABSTRACT FROM AUTHOR]

• APSIM predicted the growing period, leaf area index, biomass, and yield well. • Elevated [CO 2 ] alleviated the negative effects of warming on wheat yield. • Increased temperature and elevated [CO 2 ] mainly affected the wheat grain number. • Extreme high temperature notably affected the yield of later-maturing cultivar. • The early-maturing wheat cultivar would be better adapted to climate change. Understanding the impacts of rising temperature and elevated [CO 2 ] on different crop cultivars is critical to devising agronomic strategies and cultivar selection in the context of climate change adaptation. The growth period, biomass, and yield of two wheat cultivars (early– vs. late–maturing) were simulated by the Agricultural Production Systems sIMulator (APSIM) validated with pot experiments under the scenarios of elevated [CO 2 ] and 2 °C warming based on the baseline climate for 1961–2016 at Taigu in North China. We also investigated the effects of extreme high temperature on the yield and yield components of these wheat cultivars. We found that APSIM well simulated the changes in the growth period, leaf area index (LAI), biomass, and yield induced by 2 °C warming and elevated [CO 2 ]. Long–term simulations showed that 2 °C warming decreased the growing period between sowing and jointing for both cultivars. 2 °C warming and elevated [CO 2 ] affected the wheat yield mainly by altering the grain numbers. Extreme high temperature decreased the grain numbers and yield of the late–maturing cultivar but not the early–maturing one. The findings suggest that early–maturing cultivar would be better adapted to elevated [CO 2 ] and rising temperature than the late–maturing one in the eastern Loess Plateau. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) are a class of non-coding RNAs known to play important regulatory roles through targets, which can affect human cell proliferation, differentiation, and metabolism. Overlaps between different miRNA target prediction algorithms (MTPAs) are small, which limit the understanding of miRNA's biological functions. However, the overlaps increase on functional levels, such as Gene Ontology (GO), Protein–Protein Interaction Network (PPIN) and pathways. Here, we performed prioritization on existing predicted target sets for each miRNA by considering all the possible combinations of 7 functional levels. After analyzing the results of both single and multiple functional levels, we found that functional combination strategies including pathways and GO performed better in the prioritization of human miRNA target. The combination which performed best was “Pathway+GO BP+GO MF+GO CC+Target+PPIN”. For the prioritized result of this combination, the valid target had top ranking, and our method performed better than the MTPAs after comparison adopting the validated ranking levels. Top genes in ranking lists generated by this strategy were either validated by experiments or share same functions with the corresponding miRNA/its validated genes in disease related biological processes. [Copyright &y& Elsevier]

• Two novel chemical inhibitors of polyethylene glycol and procyanidins were investigated experimentally. • When the ratio of OPC and PEG is 1:2, the collaborative effect for preventing spontaneous combustion is significant. • Hydroxyl groups in the PEG and OPC can react with the oxide intermediate product alcohol to form stable ether bonds. • PEG and OPC are linked by hydrogen bonds to synthesize larger hydrogen proton donors, improving antioxidant activity. • When carrying OPC, PEG can cover the surface of coal, isolating coal from oxygen, keeping moisture and cooling. In order to overcome the short inhibition duration of physical inhibitor, the environmentally friendly chemical inhibitors of polyethylene glycol (PEG) and proanthocyanidin (OPC) were selected to conduct the experimental study for coal spontaneous combustion prevention. Through temperature programmed experiment, electron spin resonance experiment and Fourier infrared spectroscopy experiment, it was found that for the coal sample after treated by PEG and OPC, crossing point temperature increased by 17.6 °C and 14.3 °C, free radical concentration decreased to 0.1512 N g /1017 g−1 and 0.1178 N g /1017 g−1, association and hydroxyl free hydroxyl groups decreased by 59.72% and 24.37%, and the stability of the C O C ether bond increased by 42.71% and 18.41%, respectively, which showed the inhibition effects of both inhibitors are obvious and OPC is better. For the sample treated by OPC and PEG (ratio 1:2), crossing point temperature increased 25 °C, which indicated that the collaborative effect was remarkable. The analysis shows that PEG and OPC contain a large number of hydroxyl groups, which react with the oxide intermediate product alcohol to form ether bonds with relatively stable chemical properties, thus mitigating the rate of coal spontaneous combustion; PEG and OPC are linked by hydrogen bonds to synthesize larger hydrogen proton donors, which improved antioxidant activity. PEG is a viscous liquid, when carrying proanthocyanidin, can cover the surface of coal, isolating coal surface from oxygen, keeping moisture and cooling. The combination of the two inhibitors has significant synergistic inhibition effect, which can greatly suppress the coal spontaneous combustion. [ABSTRACT FROM AUTHOR]

The identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view. [ABSTRACT FROM AUTHOR]

High-throughput metabolomics technology, such as gas chromatography mass spectrometry, allows the analysis of hundreds of metabolites. Understanding that these metabolites dominate the study condition from biological pathway perspective is still a significant challenge. Pathway identification is an invaluable aid to address this issue and, thus, is urgently needed. In this study, we developed a network-based metabolite pathway identification method, MPINet, which considers the global importance of metabolites and the unique character of metabolomic profile. Through integrating the global metabolite functional network structure and the character of metabolomic profile, MPINet provides a more accurate metabolomic pathway analysis. This integrative strategy simultaneously captures the global nonequivalence of metabolites in a pathway and the bias from metabolomic experimental technology. We then applied MPINet to four different types of metabolite datasets. In the analysis of metastatic prostate cancer dataset, we demonstrated the effectiveness of MPINet. With the analysis of the two type 2 diabetes datasets, we show that MPINet has the potentiality for identifying novel pathways related with disease and is reliable for analyzing metabolomic data. Finally, we extensively applied MPINet to identify drug sensitivity related pathways. These results suggest MPINet's effectiveness and reliability for analyzing metabolomic data across multiple different application fields. [ABSTRACT FROM AUTHOR]