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As and Cd in soil can be assimilated and accumulated by vegetables and can be subsequently ingested by humans. Contradictory effects of organic fertilizer application on As and Cd accumulation in soil have been reported in previous studies. An eight-year greenhouse study was conducted on a sandy loam soil in Beijing, China to investigate the effects of organic fertilizer application rate on soil properties, and As and Cd accumulation in soil. The contamination risk of pak choi grown after eight years’ application of organic fertilizer was also evaluated. Soil organic carbon increased 3.0–3.8 times with low, medium and high rates of fertilizer application in 2018 compared to the initial soil. Organic fertilizer application significantly increased soil nutrients and microbial biomass while it mildly affected soil pH. The bioavailability of As/Cd has decreased after eight years’ application of organic fertilizer. Pak choi crop harvested from all three treatments in 2018 did not pose a threat to human health, even for life-time consumption. Soil total As content significantly decreased with organic fertilizer application, mainly due to the lower As content in the applied fertilizer than that in soil. Continuous application of clean organic fertilizer can be adopted to reduce the contamination risk of highly contaminated soil in the soil–plant system.

With the current study, we aimed to determine the characteristics and calcium absorption capacity of egg white peptide–calcium complex (EWP-Ca) and determine the effect of sterilization on EWP-Ca to study the possibility of EWP-Ca as a new potential calcium supplement. The results of SEM and EDS showed a high calcium chelating ability between EWP and calcium, and the structure of EWP-Ca was clustered spherical particles due its combination with calcium. The FTIR and Raman spectrum results showed that EWP could chelate with calcium by carboxyl, phosphate, and amino groups, and peptide bonds may also participate in peptide–calcium binding. Moreover, the calcium absorption of EWP-Ca measured by the intestinal everted sac model in rats was 32.38 ± 6.83 μg/mL, significantly higher than the sample with CaCl2, and the mixture of EWP and Ca (p < 0.05) revealed appropriate calcium absorption capacity. The fluorescence spectra and CD spectra showed that sterilization caused a decrease in the content of α-helix and β-sheet and a significant increase in β-turn (p < 0.05). Sterilization changed the EWP-Ca structure and decreased its stability; the calcium-binding capacity of EWP-Ca after sterilization was decreased to 41.19% (p < 0.05). Overall, these findings showed that EWP could bind with calcium, form a peptide–calcium chelate, and serve as novel carriers for calcium supplements.

The chemical composition of the cell wall varies between species and even within the same species, and impacts the properties of the cell wall. In this study, the dynamic chemical compositions of the xylem cell walls of two black poplar cultivars, Populus × euramericana ‘Zhonglin46’ and Populus × euramericana ‘Neva,’ were investigated in situ using stimulated Raman scattering microscopy (SRS). Meanwhile, the pectin structural features were examined using immunofluorescence methods. The results showed that Neva displayed faster thickening of the fiber cell walls than Zhonglin46 did, and it had a greater cell wall thickness in mature xylem. A faster deposition speed of lignin and cellulose during xylem maturation was revealed in Neva. Significantly higher lignin contents were found in the mature xylem of Neva compared with those of Zhonglin46, while no obvious differences in cellulose deposition in mature xylem were observed between the two cultivars. The patterns of pectin deposition during xylem maturation were similar in the two cultivars, but more pectin was found in the mature xylem of Neva than in that of Zhonglin46. The chemical deposition patterns account for the anatomical feature differences between the cultivars. These results provide valuable insights into the chemical deposition and anatomical differences between cultivars, and they might be helpful in understanding the wood growth processes and facilitating the utilization of different poplar cultivars.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important intracellular pathogen that poses a health threat to humans. This study tries to clarify the mechanism of Salmonella survival and reproduction in the host. In this study, high-throughput sequencing analysis was performed on RNA extracted from the strains isolated from infected mouse spleens and an S. Typhimurium reference strain (ATCC 14028) based on the BGISEQ-500 platform. A total of 1340 significant differentially expressed genes (DEGs) were screened. Functional annotation revealed DEGs associated with regulation, metabolism, transport and binding, pathogenesis, and motility. Through data mining and literature retrieval, 26 of the 58 upregulated DEGs (FPKM > 10) were not reported to be related to the adaptation to intracellular survival and were classified as candidate key genes (CKGs) for survival and proliferation in vivo. Our data contribute to our understanding of the mechanisms used by Salmonella to regulate virulence gene expression whilst replicating inside mammalian cells.

Single cell transcriptome data can be used to determine developmental lineage trajectories. Here the authors map single cell transcriptomes onto a differentiation trajectory defined by cell population transcriptomes and show that cell cycle regulators have a role in differentiation timing.

Background/Aims: The kidney plays a critical role in the control of blood pressure and its elevation in salt-induced hypertension. Mitochondrial dysfunction, especially in energy metabolism, has been associated with hypertension. Here, we aimed to investigate mitochondrial function and metabolic features in renal mitochondria of Dahl salt-sensitive (SS) rats to gain further insight into the relationship between mitochondrial metabolism and predisposition to hypertension. Methods: In this study, SS rats fed low-salt (LS) or high-salt (HS) diets were used to investigate mitochondrial function and metabolism including mitochondrial enzyme activities, pyridine nucleotides, metabolites, and oxidative stress by biochemical analysis and gas chromatography-mass spectrometer (GC-MS). Results: Significantly lower activity levels of fumarase, isocitrate dehydrogenase and succinyl-CoA synthetase were observed in renal mitochondria of SS rats compared with SS.13BN control rats fed LS diets. Intra-mitochondrial pyridine nucleotide content and mitochondrial metabolism were adversely affected in SS rats. In accordance with this, reduced ATP production, Δψm, and superoxide dismutase (SOD) activity were also observed in mitochondria of the renal medulla and cortex of SS rats. Moreover, ATP production was further impaired and oxidative stress was increased, confirming that the mitochondria of SS rats fed HS diets were dysfunctional compared to those of rats fed LS diets. Conclusions: Our data demonstrated that the renal mitochondria of SS rats exhibited complicated metabolic alteration and dysfunction in low-salt diets, and high-salt diets aggravated these dysfunctions. Thus, these results may be associated with renal dysfunction, which, in turn, would help in understanding the development of salt-sensitive hypertension.

Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13BN rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO.

This study aims to evaluate Chinese physicians’ performance of communicating with patients in a primary care setting, and to discuss barriers to improving physician–patient communication from physicians’ perspectives. Physicians’ performance in communicating with patients during primary care consultations were evaluated using a self-developed communication assessment checklist. Field observations of 7 primary care providers were conducted and their performance in 182 consultations was observed and assessed. In-depth interviews were carried out with each physician after the observations. The results of observations indicated that Chinese physicians generally performed poorly in interacting with patients and their communication style relied mainly on their personality and experience. The results of interviews revealed four barriers to improving physician–patient communication, which were the low medical literacy of patients, the high workload for physicians, the low awareness of communication skills and the adoption of defensive behaviors among physicians.

Trichinellosis is a serious foodborne zoonotic disease. It is an important threat to public health in both developing and developed countries. Human infections are strongly associated with consuming undercooked meat containing infective Trichinella larvae. The development of serological tools has enabled seroepidemiological studies and contributed to our knowledge on the importance of this parasite. Serological tests can also help the diagnosis of parasite infections in humans and the surveillance of animals. Generally speaking, serological techniques include detection methods for specific antibodies and for circulating parasite antigens in the serum or tissue fluids. Here, we present a comprehensive review of various methods used in the detection of antibodies against Trichinella and circulating parasite antigens in animals and humans.

Numerous marine reserves worldwide are losing their ability to protect wild endemic species due to surrounding ecological deterioration caused by coastal landscape artificialization. Such risk of becoming invalid nature reserves is particularly high in China's Bohai Sea coastal zone, a region with rapid urbanization and industrialization. In this study, the ecological quality (EQ) status around Laizhou Bay Ostrea rivularis germplasm reserve (R1), Yellow River Estuary Meretrix meretrix germplasm reserve (R2), and Taoer Estuary Sinonovacula constricta germplasm reserve (R3) was dynamically diagnosed using seven indicators characterizing ecological support and threat from peripheral environments. A series of thresholds indicating EQ and corresponding landscape artificialization intensity (LAI) were determined based on multi-factor clustering analysis and relational regression simulation. The results show that the surroundings of these three reserves were favorable in 1984, insufficient in 2000, and unfavorable in 2015. With an average 7.5 times increase in LAI over the past three decades, the EQ levels around R1-R3 declined significantly and have deviated greatly from their optimal reference status by 2015, which stemmed mainly from intertidal landscape artificialization, such as establishing salt pans, industrial areas and ports after reclaiming wetlands. It was found that R3 > R1 > R2 in terms of overall peripheral ecological degradation, implying that the closer the marine reserve is to the land, the more likely it is to lose its effectiveness. The changes in EQ status and LAI were well indicated by the proportion of natural ecosystems, the distance between seawalls and protected boundaries, and the reserves' enclosed degree by artificial systems, which, as a quick and simple diagnostic approach, can facilitate spatial planning and management practices around marine reserves in the Bohai Sea coastal zone and elsewhere. Keywords: Marine reserve, Surrounding environment, Ecological deterioration, Biodiversity conservation, Bohai Sea

ObjectivesAlkaline phosphatase (ALP) can promote vascular calcification, but the association between ALP and in-hospital mortality in patients with acute coronary syndrome (ACS) is not well defined.DesignA prospective cohort study.Setting and participantsA total of 6368 patients with ACS undergoing percutaneous coronary intervention (PCI) from 1 January 2010 to 31 December 2017 were analysed.Main outcome measuresIn-hospital mortality was used in this study.ResultsALP was analysed both as a continuous variable and according to three categories. After multivariable adjustment, in-hospital mortality was significantly higher in Tertile 3 group (ALP＞85 U/L) (OR: 2.399, 95% CI 1.080 to 5.333, p=0.032), compared with other two groups (Tertile 1: ＜66 U/L; Tertile 2: 66–85 U/L). When ALP was evaluated as a continuous variable, after multivariable adjustment, the ALP level was associated with an increased risk of in-hospital mortality (OR: 1.011, 95% CI 1.002 to 1.020, p=0.014). C-statistic of ALP for predicting in-hospital mortality was 0.630 (95% CI 0.618 to 0.642, p=0.001). The cut-off value was 72 U/L with a sensitivity of 0.764 and a specificity of 0.468. However, ALP could not significantly improve the prognostic performance of Global Registry of Acute Coronary Events (GRACE) score (GRACE score+ALP vs GRACE score: C-statistic: z=0.485, p=0.628; integrated discrimination improvement: 0.014, p=0.056; net reclassification improvement: 0.020, p=0.630).ConclusionsIn patients with ACS undergoing PCI, ALP was an independent predictor of in-hospital mortality. But it could not improve the prognostic performance of GRACE score.

Aiming at the lubrication problem of piston/cylinder interface of variable length, a two-dimensional mixed lubrication model was established. This model considers the adaptive eccentricity and the force balance of the piston. The calculation procedure for solving the average Reynolds equation and the nonlinear dynamic equations is established by the finite difference method and the global Newton-Raphaon method. The effects of load pressure and tilting angle of the swash plate on lubrication performance were investigated. The results show that when the supply pressure increases to the maximum, the minimum oil film thickness has a relatively small value. The results further indicate that increasing the lubrication area can decrease the inclination of the piston and the peak pressure of the oil film. Increasing the load pressure and the tilting angle of the swash plate can reduce the minimum oil film thickness and increase the friction force.

Alzheimer’s disease (AD) is a devastating disease in the elderly with no known effective treatment. It is characterized by progressive deterioration of memory and cognition. Many new potential targets are being investigated to develop effective therapeutic strategies for AD. Neuropeptide S (NPS) is an endogenous peptide in the central nervous system, which has been shown to play a beneficial role in learning and memory. However, whether NPS can ameliorate cognitive deficits in AD remains unclear. In this study, we examined the effects of NPS treatment on the cognitive behaviors and pathological hallmarks in 8-month-old APPswe/PS1dE9 (APP/PS1) AD mice. We found that the APP/PS1 mice exhibited lower levels of NPS receptors (NPSRs) in the hippocampal area, and NPS administration increased c-Fos expression in the hippocampus and cortex, which suggests the NPS/NPSR system may contribute to the pathogenesis of AD. After an intracerebroventricular injection of NPS (1 nmol) for 2 weeks, we found NPS treatment ameliorated spatial memory deficits and promoted dendrite ramification and spine generation in hippocampal CA1 neurons, which was accompanied by the upregulation of postsynaptic density protein 95 (PSD95) and synapsin1. We also demonstrated that the injection of NPS decreased Aβ plaque deposits by decreasing the γ-secretase activity and the phosphorylation of APP at Thr668. Furthermore, application of NPS reversed the deficits in hippocampal late-phase long-term potentiation (LTP). These findings suggest NPS attenuated cognitive deficits by reducing pathological features in APP/PS1 mice, and NPS might be a potential therapeutic agent for AD.

With the rapid rising of global population, the demand for improving breeding techniques to greatly increase the worldwide crop production has become more and more urgent. Most researchers believe that the key to new breeding techniques lies in genetic improvement of crops, which leads to a large quantity of phenotyping spots. Unfortunately, current phenotyping solutions are not powerful enough to handle so many spots with satisfying speed and accuracy. As a result, high-throughput phenotyping is drawing more and more attention. In this paper, we propose a new field-based sensing solution to high-throughput phenotyping. We mount a LiDAR (Velodyne HDL64-S3) on a mobile robot, making the robot a “phenomobile.” We develop software for data collection and analysis under Robotic Operating System using open source components and algorithm libraries. Different from conducting phenotyping observations with an in-row and one-by-one manner, our new solution allows the robot to move around the parcel to collect data. Thus, the 3D and 360° view laser scanner can collect phenotyping data for a large plant group at the same time, instead of one by one. Furthermore, no touching interference from the robot would be imposed onto the crops. We conduct experiments for maize plant on two parcels. We implement point cloud merging with landmarks and Iterative Closest Points to cut down the time consumption. We then recognize and compute the morphological phenotyping parameters (row spacing and plant height) of maize plant using depth-band histograms and horizontal point density. We analyze the cloud registration and merging performances, the row spacing detection accuracy, and the single plant height computation accuracy. Experimental results verify the feasibility of the proposed solution.

Although the activation of pathogen phagocytosis via complement system has been studied, erythrocyte-phagocyte interactions in pigs are not clearly understood. Therefore, we sought to investigate the ability of porcine erythrocytes to clear immune complexes (ICs) by using laser confocal microscopy and flow cytometry to observe the immune adhesion of porcine erythrocytes to fluorescent bacilli and the immune presentation process of transferring fluorescent bacilli to macrophages. Isolated porcine alveolar macrophages (PAMs) had uniform morphology and size, and a survival rate of 97.2%. The phagocytosis rate was 98.8%. After WT E. coli was labeled with Fluorescein Isothiocyanate (FITC), the bacteria showed a bright green fluorescence, and the labeling rate was 92.3%. When laser confocal microscopy was utilized to observe the co-incubation system of porcine erythrocytes, PAM, and fluorescent E. coli, the fluorescence intensity of bacilli decreased with increasing observation time and even disappeared. Flow Cytometry examination showed that the average fluorescence intensity of PAMs co-incubated with porcine erythrocytes adhered to WT-E. coli-FITC, was significantly higher than that of normal PAMs. Furthermore, when porcine erythrocytes adhered to WT E. coli were incubated with PAMs, the surface mean fluorescence intensity of porcine erythrocytes was significantly higher than that of the blank control group. This shows that PAMs can competitively bind to the oposinized E. coli adhered to the surface of porcine erythrocytes, and these oposinized pathogens can enter macrophages by the process of phagocytosis, which promoting the internalization of ICs or pathogens. During this process, the physical morphology of porcine erythrocytes was not damaged, but the levels of its main functional protein CR1-like were reduced.

The purpose of this paper is to investigate the impact of risk and competition on the profitability of the Pakistani banking industry. Data are retrieved from the annual statements of banks, the Ministry of finance Pakistan and the World Bank covering the period of (2007-2017). Two steps Generalized Method of Moments (GMM) with the collapse command is used as an estimation technique to overcome endogeneity, unobserved heterogeneity and autocorrelation problems. The results of the study showed that the liquidity risk has positive while credit risk, insolvency risk and competition hurt negatively the profitability of Pakistani banks. The results of the study also revealed that capitalization, size, taxation and GDP growth rate positively affect the Banks' profits while banking sector development and infrastructure negatively affect banking profitability in Pakistan. The operational cost management positively affects net interest margins but negatively affects ROA and PBT in the Pakistani banking industry.

Moisture absorbed into shrimp hydrolysates (SHs) flour profoundly affected its properties. The unstored hydrolysate flour was called SHs-0h and SHs stored for 30 h at 25 °C and 75% relative humidity was named SHs-30. During the process of storage, the moisture dynamics in SHs flour were investigated by dynamic vapor sorption (DVS) and low-field nuclear magnetic resonance (LF-NMR). The effects of moisture absorption on the radicals scavenging rates of SHs flour were evaluated by electron paramagnetic resonance (EPR). The effects of moisture absorption on secondary structure were studied by mid-infrared (MIR) spectroscopy and infrared microimaging spectroscopy. The changes of volatile components were monitored by purge and trap coupled with gas chromatography-mass spectrometry (PT-GC-MS). DVS results showed that the moisture absorption rate of SHs flour could reach a maximum of 88.93%. Meanwhile, the water was transformed into more stable water with shorter relaxation times. The porous structure of the SHs-30 h flour disappeared and became smoother compared to SH-0 h flour. DPPH (31.09 ± 0.54%) and OH (26.62 ± 1.14%) radicals scavenging rates of SHs-30 h significantly reduced (p < 0.05) compared to that of SHs-0 h flour. The vibrations of the MIR absorbance peaks were changed. Finally, eight volatile components disappeared and six new volatile compounds were found. This study provided a theory basis for moisture dynamics in peptide flour during the storage process.

The objective of this study was to verify the supposition that efflux might be involved in the drug resistance of Riemerella anatipestifer isolates. Two broad-spectrum efflux pump inhibitors, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and Phe-Arg-β-naphthylamide (PAβN), on the contribution of minimum inhibitory concentrations of amikacin, streptomycin, chloramphenicol, tetracycline, ceftriaxone, ceftazidime, nalidixic acid, levofloxacin, enrofloxacin, as well as ciprofloxacin against 69 clinical R. anatipestifer isolates were investigated. We first reported that the two efflux pump inhibitors could restore the antimicrobial susceptibility of R. anatipestifer isolates. It is suggested that active efflux system is possible to be linked with the development of resistance in R. anatipestifer isolates.

Osthole (Ost) is an active constituent of Cnidium monnieri (L.) Cusson which possesses anti-inflammatory and anti-oxidative properties. It also has estrogen-like activity and can stimulate corticosterone secretion. The present study was aimed to check the role of Ost on progesterone (P4) secretion in cultured granulosa cells obtained from hen preovulatory follicles. Different concentrations (5, 2.5, and 1.25 µg/mL) of Ost was added to granulosa cells for 6, 12, 18, and 24 h to investigate the level of progesterone secretions using enzyme linked immunosorbent assay (ELISA). The results showed that progesterone secretion was significantly increased in cells treated with Ost at 2.5 μg/mL. Also, qRT-PCR showed that mRNA expression of steroidogenic acute regulatory protein (StAR) was significantly up-regulated by Ost at 2.5 μg/mL concentration. Cytochrome P450 side-chain cleavage (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD) was significantly up-regulated by Ost. However, no significant differences were observed for the expression of proliferating cell nuclear antigen (PCNA). The protein expression of StAR, P450scc and 3β-HSD were significantly up-regulated by Ost treatment. The concentration of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in cell lysates showed no change with Ost treatment at 2.5 μg/mL by ELISA. An ROS kit showed non-significant difference in the level of reactive oxygen species (ROS). In conclusion, Ost treatment at a concentration of 2.5 μg/mL for 24 h had significantly up-regulated P4 secretion by elevating P450scc, 3β-HSD and StAR at both gene and protein level in granulosa cells obtained from hen preovulatory follicles.

The Three Gorges Reservoir (TGR) intervening basin is one of the most important, ecologically fragile and sensitive areas in the upper reaches of the Yangtze River. Since the completion and operation of the TGR, the change of the ecological environment in this region—with vegetation as an indicator—has been a consistent focus of attention. Based on the six phases of land use data and normalized difference vegetation index (NDVI), temperature and precipitation data from 1998 to 2017, the change and trend of land use and vegetation cover in the TGR intervening basin were analyzed quantitatively by using a transition matrix, linear regression and partial correlation analysis. The area of unchanged land use type is 56,565 km2, accounting for 97.27% of the total area of the basin. The vegetation coverage with NDVI as the indicator showed a significant upward trend, with a growth rate of 7.5%/10a. The impact of temperature on vegetation was greater than that of precipitation on vegetation. The non-linear fitting curve of NDVI to temperature and precipitation rose with the time course of TGR impoundment, although the mechanism remains to be studied further. In general, climate change, ecological restoration measures, urbanization and reservoir impoundment did not significantly change the spatial distribution pattern of land use and the climate driving mechanism of vegetation growth in the TGR intervening basin.

Recently released potato cultivars Dakota Russet and Easton were bred for low reducing sugars, and low acrylamide-forming potential in French fries. The objectives of this study were to determine: (1) the effects of nitrogen rate and storage time on tuber glucose concentrations in different cultivars; (2) the relationships between acrylamide, glucose, and asparagine for the new cultivars and Russet Burbank. The study was conducted at Becker, Minnesota over a period of two years on a loamy sand soil under irrigated conditions. All cultivars were subjected to five N rates from 135 to 404 kg ha−1 in a randomized complete block design. Following harvest, tubers were stored at 7.8 °C and sampled at 0, 16, and 32 weeks. Dakota Russet and Easton had significantly lower concentrations of stem- and bud-end glucose, asparagine, and acrylamide than those of Russet Burbank in both years. The effect of storage time on glucose concentration was significant but differed with cultivar and year. N rate effects on stem- and bud-end glucose concentrations were cultivar and storage time dependent. After 16 weeks of storage, both asparagine and acrylamide concentrations linearly increased with increasing N rate. Glucose concentration was positively correlated with acrylamide concentration (r2 = 0.61). Asparagine concentration was also positively correlated with acrylamide concentration (r2 = 0.45) when the asparagine:glucose ratio was

Summary: Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations’ non-tissue-specific “core transcriptome signatures” (CSs) of 8,476 genes generated from the TCGA database. We developed the core-signature drug-to-gene (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures. csD2G significantly outperformed conventional cell line-based gene perturbation signatures and existing drug-repositioning methods in both coverage and specificity. We highlight this with 3 demonstrated applications: (1) repositioned category of psychiatric drugs to inhibit the TGF-β pathway; (2) antihypertensive calcium channel blockers predicted to activate AMPK and inhibit AKT pathways, and validated by clinical electronic medical records; and (3) 7 drugs predicted and validated to selectively target the AKT-FOXO and AMPK pathways and thus regulate worm lifespan. : Xu et al. generated core transcriptome signatures representing single-gene mutations for 8,476 human genes from the cancer transcriptomes in the TCGA database and developed a drug-repositioning method to predict high-specificity candidate target genes for 1,938 drugs. Applied to targeting aging pathways, 7 lifespan-extending drugs are found and functionally validated. Keywords: drug repositioning, drug target, cancer genomics, data integrative analysis

Neuropathic pain (NP) is a type of chronic pain that is different from the common type of pain. The mechanisms of NP are still poorly understood. Exploring the key genes and neurobiological changes in NP could provide important diagnostic and treatment tools for clinicians. GSE24982 is an mRNA-seq dataset that we downloaded from the Gene Expression Omnibus database to identify key genes in NP. Differentially expressed genes (DEGs) were identified using the BRB-ArrayTools software and R. Functional and pathway enrichment analyses of the DEGs were performed using Metascape. A protein–protein interaction network was created and visualized using Cytoscape. A total of 123 upregulated DEGs were obtained. Among these genes, p53 was the node with the highest degree; hence, we validated it experimentally using a chronic constriction injury mouse model. Our results showed that overexpression of the p53 gene, and the subsequent increase in caspase-3 expression, in dorsal root ganglion neurons led to increased apoptotic changes in these neurons. p53 may therefore be partly responsible for the development of chronic constriction injury-induced NP.

A simple and novel method has been proposed to determine the enantiomeric composition of racemate praziquantel (PZQ) by using the analysis of ultraviolet (UV) spectroscopy combined with partial least squares (PLS). This method does not rely on the use of expensive carbohydrates such as cyclodextrins, but on the use of inexpensive sucrose, which is equally effective as carbohydrate. PZQ has two enantiomers. Through measuring the slight difference in the UV spectral absorption of PZQ due to different interactions between its two enantiomers and sucrose, the enantiomeric composition was determined by a quantitative model based on PLS analysis. The model showed that the correlation coefficients of calibration set and validation set were 0.9971 and 0.9972, respectively. The root mean square error of calibration (RMSEC) and the root mean square error of prediction (RMSEP) were 0.0167 and 0.0129, respectively. Then, the independent data of PZQ tablets were also used to test how well the quantitative model of PLS predicted the enantiomeric composition. The ratio of S-PZQ in tablet was 0.492, determined by high-performance liquid chromatography as the reference value. Six solutions of the tablet samples were prepared, and the ratios of S-PZQ in tablet samples in the validation set were predicted by the PLS model. Their relative errors with the reference value were not more than 4%. Therefore, the established model could be accurate and employed to predict the enantiomeric compositions of PZQ tablets.

Canine distemper virus (CDV), a paramyxovirus, causes a severe highly contagious lethal disease in carnivores, such as mink. Mink lung epithelial cells (Mv.1.Lu cells) are sensitive to CDV infection and are homologous to the natural host system of mink. The current study analyzed the response of Mv.1.Lu cells to CDV infection by iTRAQ combined with LC–MS/MS. In total, 151 and 369 differentially expressed proteins (DEPs) were markedly up-regulated or down-regulated, respectively. Thirteen DEPs were validated via real-time RT-PCR or western blot analysis. Network and KEGG pathway analyses revealed several regulated proteins associated with the NF-κB signaling pathway. Further validation was performed by western blot analysis and immunofluorescence assay, which demonstrated that different CDV strains induced NF-κB P65 phosphorylation and nuclear translocation. Moreover, the results provided interesting information that some identified DEPs possibly associated with the pathogenesis and the immune response upon CDV infection. This study is the first overview of the responses to CDV infection in Mv.1.Lu cells, and the findings will help to analyze further aspects of the molecular mechanisms involved in viral pathogenesis and the immune responses upon CDV infection.

Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content. Additionally, metabolite profiling was conducted using gas chromatography combined with time-of-flight mass spectrometry (GC/TOF-MS). Phenotypically, the RI alfalfa exhibited a greater resistance to alkali stress than the NI plants examined. Physiological analysis and metabolic profiling revealed that RI plants accumulated more antioxidants (SOD, POD, GSH), osmolytes (sugar, glycols, proline), organic acids (succinic acid, fumaric acid, and alpha-ketoglutaric acid), and metabolites that are involved in nitrogen fixation. Our pairwise metabolomics comparisons revealed that RI alfalfa plants exhibited a distinct metabolic profile associated with alkali putative tolerance relative to NI alfalfa plants. Data provide new information about the relationship between non-nodulized, rhizobium-nodulized alfalfa and alkali resistance.

By using sample units (SUs), the generalized data envelopment analysis (DEA) method can evaluate the efficiency of decision making unit (DMU) through different reference sets, but the existing models are radial models, and the DMU is treated as a black box, rarely taking the operations of the internal divisions into account. This paper proposes a generalized network slacks-based measure (SBM) approach based on the SUs. First, the generalized network SBM approach for a basic two-stage structure is proposed. This paper considers the intermediate products in calculating the divisional efficiency for each DMU. Overall efficiency of DMU is a weighted average of the divisional efficiency. The weight of each division does not need to be given in advance. Since the DMUs set and SUs set are not necessarily the same, this paper proposes an improved generalized network SBM approach for a basic two-stage structure to solve the problem that the original model may be infeasible. Then, the approach for basic two-stage structure is extended to general multi-stage structure. Finally, an example is given to show the practicability of the generalized network SBM approach.

Consistent streamflow forecasts play a fundamental part in flood risk mitigation. Population increase and water cycle intensification are extending not only globally but also among Pakistan’s water resources. The frequency of floods has increased in the last few decades in the country, which emphasizes the importance of efficient practices needed to adopt for various aspects of water resource management such as reservoir scheduling, water sustainability, and water supply. The purpose of this study is to develop a novel hybrid model for streamflow forecasting and validate its efficiency at the upper Indus basin (UIB), Pakistan. Maximum streamflow in the River Indus from its upper mountain basin results from melting snow or glaciers and climatic unevenness of both precipitation and temperature inputs, which will, therefore, affect rural livelihoods at both a local and a regional scale through effects on runoff in the Upper Indus basin (UIB). This indicates that basins receive the bulk of snowfall input to sustain the glacier system. The present study will help find the runoff from high altitude catchments and estimated flood occurrence for the proposed and constructed hydropower projects of the Upper Indus basin (UIB). Due to climate variability, the upper Indus basin (UIB) was further divided into three zone named as sub-zones, zone one (z1), zone two (z2), and zone three (z3). The hybrid models are designed by incorporating artificial intelligence (AI) models, which includes Feedforward backpropagation (FFBP) and Radial basis function (RBF) with decomposition methods. This includes a discrete wavelet transform (DWT) and ensemble empirical mode decomposition (EEMD). On the basis of the autocorrelation function and the cross-correlation function of streamflow, precipitation and temperature inputs are selected for all developed models. Data have been analyzed by comparing the simulation outputs of the models with a correlation coefficient (R), root mean square errors (RMSE), Nash-Sutcliffe Efficiency (NSE), mean absolute percentage error (MAPE), and mean absolute errors (MAE). The proposed hybrid models have been applied to monthly streamflow observations from three hydrological stations and 17 meteorological stations in the UIB. The results show that the prediction accuracy of the decomposition-based models is usually better than those of AI-based models. Among the DWT and EEMD based hybrid model, EEMD has performed significantly well when compared to all other hybrid and individual AI models. The peak value analysis is also performed to confirm the results’ precision rate during the flood season (May-October). The detailed comparative analysis showed that the RBFNN integrated with EEMD has better forecasting capabilities as compared to other developed models and EEMD-RBF can capture the nonlinear characteristics of the streamflow time series during the flood season with more precision.

Appropriate neural initiation of the pluripotent stem cells in the early embryos is critical for the development of the central nervous system. This process is regulated by the coordination of extrinsic signals and intrinsic programs. However, how the coordination is achieved to ensure proper neural fate commitment is largely unknown. Here, taking advantage of genome-wide ChIP-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) analyses, we demonstrate that the transcriptional factor Pou3f1 is an upstream activator of neural-promoting genes, and it is able to repress neural-inhibitory signals as well. Further studies revealed that Pou3f1 could directly bind neural lineage genes like Sox2 and downstream targets of neural inhibition signaling such as BMP and Wnt. Our results thus identify Pou3f1 as a critical dual-regulator of the intrinsic transcription factors and the extrinsic cellular signals during neural fate commitment. Data were deposited in Gene Expression Omnibus (GEO) datasets under reference number GSE69865.

Ovarian cancer has a poor prognosis, with different outcomes for different patients. The mechanism underlying this poor prognosis and heterogeneity is not well understood. We have developed an unbiased, adaptive clustering approach to integratively analyze ovarian cancer genome-wide gene expression, DNA methylation, microRNA expression, and copy number alteration profiles. We uncovered seven previously uncategorized subtypes of ovarian cancer that differ significantly in median survival time. We then developed an algorithm to uncover molecular signatures that distinguish cancer subtypes. Surprisingly, although the good-prognosis subtypes seem to have not been functionally selected, the poor-prognosis ones clearly have been. One subtype has an epithelial–mesenchymal transition signature and a cancer hallmark network, whereas the other two subtypes are enriched for a network centered on SRC and KRAS. Our results suggest molecular signatures that are highly predictive of clinical outcomes and spotlight “driver” genes that could be targeted by subtype-specific treatments.

Flood forecasting plays an important role in flood control and water resources management. Recently, the data-driven models with a simpler model structure and lower data requirement attract much more attentions. An extreme learning machine (ELM) method, as a typical data-driven method, with the advantages of a faster learning process and stronger generalization ability, has been taken as an effective tool for flood forecasting. However, an ELM model may suffer from local minima in some cases because of its random generation of input weights and hidden layer biases, which results in uncertainties in the flood forecasting model. Therefore, we proposed an improved ELM model for short-term flood forecasting, in which an emerging dual population-based algorithm, named backtracking search algorithm (BSA), was applied to optimize the parameters of ELM. Thus, the proposed method is called ELM-BSA. The upper Yangtze River was selected as a case study. Several performance indexes were used to evaluate the efficiency of the proposed ELM-BSA model. Then the proposed model was compared with the currently used general regression neural network (GRNN) and ELM models. Results show that the ELM-BSA can always provide better results than the GRNN and ELM models in both the training and testing periods. All these results suggest that the proposed ELM-BSA model is a promising alternative technique for flood forecasting.

Nanocarriers encapsulating multiple chemotherapeutics are a promising strategy to achieve combinational chemotherapy for cancer therapy; however, they generally use exotic new carriers without therapeutic effect, which usually suffer from carrier-related toxicity issues, as well as having to pass extensive clinical trials to be drug excipients before any clinical applications. Cargo-free nanomedicines, which are fabricated by drugs themselves without new excipients and possess nanoscale characteristics to realize favorable pharmacokinetics and intracellular delivery, have been rapidly developed and drawn much attention to cancer treatment. Herein, we discuss recent advances of cargo-free nanomedicines for cancer treatment. After a brief introduction to the major types of carrier-free nanomedicine, some representative applications of these cargo-free nanomedicines are discussed, including combination therapy, immunotherapy, as well as self-monitoring of drug release. More importantly, this review draws a brief conclusion and discusses the future challenges of cargo-free nanomedicines from our perspective.

The purpose of a flood control reservoir operation is to prevent flood damage downstream of the reservoir and the safety of the reservoir itself. When a single reservoir cannot provide enough storage capacity for certain flood control points downstream, cascade reservoirs should be operated together to protect these areas from flooding. In this study, for efficient use of the reservoir storage, an optimal flood control operation model of cascade reservoirs for certain flood control points downstream was proposed. In the proposed model, the upstream reservoirs with the optimal operation strategy were considered to reduce the inflow of the reservoir downstream. For a large river basin, the flood routing and time-lag cannot be neglected. So, dynamic programming (DP) combined with the progressive optimality algorithm (POA) method, DP-POA, was proposed. Thus, the innovation of this study is to propose a two-stage optimal reservoir operation model with a DP-POA algorithm to solve the problem of optimal co-operation of cascade reservoirs for multiple flood control points downstream during the flood season. The upper Yangtze River was selected as a case study. Three reservoirs from upstream to downstream, Xiluodu, Xiangjiaba and the Three Gorges reservoirs (TGR) in the upper Yangtze River, were taken into account. Results demonstrate that the two-stage optimization algorithm has a good performance in solving the cascade reservoirs optimization problem, because the inflow of reservoir downstream and the division volumes were largely reduced. After the optimal operation of Xiluodu and Xiangjiaba reservoirs, the average reduction of flood peak for all these 13 typical flood hydrographs (TFHs) is 13.6%. Meanwhile, the cascade reservoirs can also store much more storm water during a flood event, and the maximum volumes stored in those two reservoirs upstream in this study can reach 25.2 billion m3 during a flood event. Comprising the proposed method with the current operation method, results demonstrate that the flood diversion volumes at the flood control points along the river decrease significantly.

Due to inherent randomness and fluctuation of wind speeds, it is very challenging to develop an effective and practical model to achieve accurate wind speed forecasting, especially over large forecasting horizons. This paper presents a new decomposition-optimization model created by integrating Variational Mode Decomposition (VMD), Backtracking Search Algorithm (BSA), and Regularized Extreme Learning Machine (RELM) to enhance forecasting accuracy. The observed wind speed time series is firstly decomposed by VMD into several relative stable subsequences. Then, an emerging optimization algorithm, BSA, is utilized to search the optimal parameters of the RELM. Subsequently, the well-trained RELM is constructed to do multi-step (1-, 2-, 4-, and 6-step) wind speed forecasting. Experiments have been executed with the proposed method as well as several benchmark models using several datasets from a widely-studied wind farm, Sotavento Galicia in Spain. Additionally, the effects of decomposition and optimization methods on the final forecasting results are analyzed quantitatively, whereby the importance of decomposition technique is emphasized. Results reveal that the proposed VMD-BSA-RELM model achieves significantly better performance than its rivals both on single- and multi-step forecasting with at least 50% average improvement, which indicates it is a powerful tool for short-term wind speed forecasting.

This paper introduces three artificial neural network (ANN) architectures for monthly streamflow forecasting: a radial basis function network, an extreme learning machine, and the Elman network. Three ensemble techniques, a simple average ensemble, a weighted average ensemble, and an ANN-based ensemble, were used to combine the outputs of the individual ANN models. The objective was to highlight the performance of the general regression neural network-based ensemble technique (GNE) through an improvement of monthly streamflow forecasting accuracy. Before the construction of an ANN model, data preanalysis techniques, such as empirical wavelet transform (EWT), were exploited to eliminate the oscillations of the streamflow series. Additionally, a theory of chaos phase space reconstruction was used to select the most relevant and important input variables for forecasting. The proposed GNE ensemble model has been applied for the mean monthly streamflow observation data from the Wudongde hydrological station in the Jinsha River Basin, China. Comparisons and analysis of this study have demonstrated that the denoised streamflow time series was less disordered and unsystematic than was suggested by the original time series according to chaos theory. Thus, EWT can be adopted as an effective data preanalysis technique for the prediction of monthly streamflow. Concurrently, the GNE performed better when compared with other ensemble techniques.

Power transformer is an essential component in the power systems. The concentration of fault characteristic gases dissolved transformer oil is essential to the insulation fault diagnosis. The concentration prediction of the gases is an important supplement for periodical testing. A NMGM(1, 5)model using Nou-equidistance Multivariable grey theory for the five characteristic gases dissolved in transformer oil, i.e. hydrogen, methane, ethane, ethylene, acetylene, was constructed. In the built model, the interaction among these gases was comprehensively considered and the disadvantage that only one index extracted from the signal or each index that was dealt with separately was made up, meanwhile, the scope of application is enlarged. Two actual prediction cases were analyzed and the results were compared with those obtained by Non-equidistant GM(1, l)model. The comparison result indicates the validity and efficiency of the proposed model.

In the present work, a novel photocatalytic fuel cell (PFC) system involving a dual heterojunction photoelectrodes, viz. polyaniline/TiO2 nanotubes (PANI/TiO2 NTs) photoanode and CuO/Co3O4 nanorods (CuO/Co3O4 NRs) photocathode, has been designed. Compared to TiO2 NTs electrode of PFC, the present heterojunction design not only enhances the visible light absorption but also offers the higher efficiency in degrading Rhodamine B–a model organic pollutant. The study includes an evaluation of the dual performance of the photoelectrodes as well. Under visible-light irradiation of 3 mW cm−2, the cell composed of the photoanode PANI/TiO2 NTs and CuO/Co3O4 NRs photocathode forms an interior bias of +0.24 V within the PFC system. This interior bias facilitated the transfer of electrons from the photoanode to photocathode across the external circuit and combined with the holes generated therein along with a simultaneous power production. In this manner, the separation of electron/hole pair was achieved in the photoelectrodes by releasing the holes and electrons of PANI/TiO2 NTs photoanode and CuO/Co3O4 NRs photocathode, respectively. Using this PFC system, the degradation of Rhodamine B in aqueous media was achieved to an extent of 68.5% within a reaction duration of a four-hour period besides a simultaneous power generation of 85 μA cm−2.

A hallmark of Alzheimer's disease (AD) is the accumulation of extracellular amyloid-β (Aβ) plaques in the brains of patients. N-terminally truncated pyroglutamate-modified Aβ (pEAβ) has been described as a major compound of Aβ species in senile plaques. pEAβ is more resistant to degradation, shows higher toxicity and has increased aggregation propensity and β-sheet stabilization compared to non-modified Aβ. Here we characterized recombinant pEAβ(3-40) in aqueous trifluoroethanol (TFE) solution regarding its aggregation propensity and structural changes in comparison to its non-pyroglutamate-modified variant Aβ(1-40). Secondary structure analysis by circular dichroism spectroscopy suggests that pEAβ(3-40) shows an increased tendency to form β-sheet-rich structures in 20% TFE containing solutions where Aβ(1-40) forms α-helices. Aggregation kinetics of pEAβ(3-40) in the presence of 20% TFE monitored by thioflavin-T (ThT) assay showed a typical sigmoidal aggregation in contrast to Aβ(1-40), which lacks ThT positive structures under the same conditions. Transmission electron microscopy confirms that pEAβ(3-40) aggregated to large fibrils and high molecular weight aggregates in spite of the presence of the helix stabilizing co-solvent TFE. High resolution NMR spectroscopy of recombinantly produced and uniformly isotope labeled [U-15N]-pEAβ(3-40) in TFE containing solutions indicates that the pyroglutamate formation affects significantly the N-terminal region, which in turn leads to decreased monomer stability and increased aggregation propensity.

An outbreak of Streptococcus suis serotype 2 emerged in the summer of 2005 in Sichuan Province, and sporadic infections occurred in 4 additional provinces of China. In total, 99 S. suis strains were isolated and analyzed in this study: 88 isolates from human patients and 11 from diseased pigs. We defined 98 of 99 isolates as pulse type I by using pulsed-field gel electrophoresis analysis of SmaI-digested chromosomal DNA. Furthermore, multilocus sequence typing classified 97 of 98 members of the pulse type I in the same sequence type (ST), ST-7. Isolates of ST-7 were more toxic to peripheral blood mononuclear cells than ST-1 strains. S. suis ST-7, the causative agent, was a single-locus variant of ST-1 with increased virulence. These findings strongly suggest that ST-7 is an emerging, highly virulent S. suis clone that caused the largest S. suis outbreak ever described.

Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam (1), together with the previously reported compounds cis-N-feruloyl-3-O-methyldopamine (2) and trans-N-feruloyl-3-O-methyldopamine (3). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS) were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G1 fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G1 fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima.

The neural fate commitment of pluripotent stem cells requires the repression of extrinsic inhibitory signals and the activation of intrinsic positive transcription factors. However, how these two events are integrated to ensure appropriate neural conversion remains unclear. In this study, we showed that Pou3f1 is essential for the neural differentiation of mouse embryonic stem cells (ESCs), specifically during the transition from epiblast stem cells (EpiSCs) to neural progenitor cells (NPCs). Chimeric analysis showed that Pou3f1 knockdown leads to a markedly decreased incorporation of ESCs in the neuroectoderm. By contrast, Pou3f1-overexpressing ESC derivatives preferentially contribute to the neuroectoderm. Genome-wide ChIP-seq and RNA-seq analyses indicated that Pou3f1 is an upstream activator of neural lineage genes, and also is a repressor of BMP and Wnt signaling. Our results established that Pou3f1 promotes the neural fate commitment of pluripotent stem cells through a dual role, activating internal neural induction programs and antagonizing extrinsic neural inhibitory signals.