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Context: Computational drug repurposing methods have been continuously developed in recent years to alleviate the high costs associated with drug development. As drug targets or the products of disease-related genes, proteins play an important role in drug repurposing. Although the potential has been demonstrated, heterogeneous graphs with proteins as independent nodes have yet to be studied, where extracting high-quality protein features from heterogeneous graphs poses a significant challenge. A novel drug repurposing model based on the feature construction of multi-layer ensemble (DRML-Ensemble) is proposed in this study. The performance of DRML-Ensemble, as evaluated on publicly available datasets, achieves an AUPR value of 0.93 and an AUROC value of 0.92, surpassing those of existing state-of-the-art methods. Additionally, DRML-Ensemble demonstrates its notable ability for drug repurposing in Alzheimer's disease. Methods: DRML-Ensemble is primarily composed of multiple layers of heterogeneous graph feature construction (HGFC). Each HGFC can extract protein features by leveraging the relationships between drugs, diseases, and proteins. These protein features are then utilized in subsequent layers to build drug and disease features, facilitating drug repurposing. By stacking multiple layers, optimal protein features can be obtained from the heterogeneous graph, consequently improving the accuracy of drug repurposing. However, an excessive· stacking of layers usually affect the model's training process, for example, causing problems such as overfitting; a multi-layer ensemble prediction module is designed to further improve the model's performance. [ABSTRACT FROM AUTHOR]

Although our knowledge of autism spectrum disorder (ASD) has been deepened, the accurate diagnosis of ASD from normal individuals is still left behind. In this study, we proposed to apply the spatial pattern of the network topology (SPN) to identify children with ASD from normal ones. Based on two independent batches of electroencephalogram datasets collected separately, the accurate recognition of ASD from normal children was achieved by applying the proposed SPN features. Since decreased long-range connectivity was identified for children with ASD, the SPN features extracted from the distinctive topological architecture between two groups in the first dataset were used to validate the capacity of SPN in classifying ASD, and the SPN features achieved the highest accuracy of 92.31%, which outperformed the other features e.g., power spectrum density (84.62%), network properties (76.92%), and sample entropy (73.08%). Moreover, within the second dataset, by using the model trained in the first dataset, the SPN also acquired the highest sensitivity in recognizing ASD, when compared to the other features. These results consistently illustrated that the functional brain network, especially the intrinsic spatial network topology, might be the potential biomarker for the diagnosis of ASD. [ABSTRACT FROM AUTHOR]

Purpose: Sleep apnea-specific hypoxic burden (SASHB) is a polysomnographic metric that comprehensively measures the degree of nocturnal desaturation caused by obstructive sleep apnea. This research was conducted to elucidate the relationship between SASHB and coronary artery disease (CAD) severity. Methods: We carried out a prospective study of hospitalized patients with CAD of unstable angina who were expected to undergo invasive coronary angiography at Beijing Anzhen Hospital from February to September 2023. SASHB values were calculated using a self-programmed C + + program. Multivariable logistic regression analysis was applied to identify the association between SASHB and the prevalence of severe CAD, documented by the Gensini Score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) Score. Results: This study enrolled 137 patients with a median age of 59 years, 96 (70.1%) of whom were male. A total of 125 (91.2%) patients had coronary stenosis of ≥ 50% in at least one location. Patients with a high SASHB of ≥ 18% min/h had a significantly higher Gensini Score (32.0 vs. 18.5, P = 0.002) and SYNTAX Score (14.0 vs. 7.0, P = 0.002) than those with a low SASHB. After adjusting for multiple covariates, a high SASHB was significantly associated with the prevalence of severe CAD, determined by a Gensini Score ≥ 21 (OR 2.67, P = 0.008) or a SYNTAX Score > 22 (OR 4.03, P = 0.016). Conclusion: Our findings revealed a robust and independent association between SASHB and CAD severity in patients with unstable angina, highlighting the potential value of SASHB as a predictor of risk and a target for interventions aimed at preventing cardiovascular diseases. Trial registration: Chinese Clinical Trial Registry No. ChiCTR2300067991 on February 2, 2023. [ABSTRACT FROM AUTHOR]

Background: The study aimed to establish a link between blood ethylene oxide (EO) levels and periodontitis, given the growing concern about EO’s detrimental health effects. Materials and methods: The study included 1006 adults from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) dataset. We assessed periodontitis prevalence across groups, used weighted binary logistic regression and restricted cubic spline fitting for HbEO-periodontitis association, and employed Receiver Operating Characteristic (ROC) curves for prediction. Results: In the periodontitis group, HbEO levels were significantly higher (40.57 vs. 28.87 pmol/g Hb, P < 0.001). The highest HbEO quartile showed increased periodontitis risk (OR = 2.88, 95% CI: 1.31, 6.31, P = 0.01). A “J”-shaped nonlinear HbEO-periodontitis relationship existed (NL-P value = 0.0116), with an inflection point at ln-HbEO = 2.96 (EO = 19.30 pmol/g Hb). Beyond this, ln-HbEO correlated with higher periodontitis risk. A predictive model incorporating sex, age, education, poverty income ratio, alcohol consumption, and HbEO had 69.9% sensitivity and 69.2% specificity. The model achieved an area under the ROC curve of 0.761. Conclusions: These findings suggest a correlation between HbEO levels and an increased susceptibility to periodontitis. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common malignancy in children and adolescents and has a high probability of recurrence and metastasis. A growing number of studies have shown that neutrophil extracellular traps (NETs) are strongly associated with cancer metastasis, but in osteosarcoma, genes associated with NETs that promote osteosarcoma recurrence and metastasis remain to be explored. We systematically investigated the gene expression patterns of NETs in OS samples from the GEO database. NETs molecular typing was evaluated based on NETs expression profiles, and the association between NETs molecular subtypes and immune microenvironment and metastatic features were explored. Ultimately, we constructed a signature model and column line graph associated with metastasis prediction and screened possible potential drugs for metastatic osteosarcoma. We established two different molecular subtypes of NETs, which showed significant differences in metastatic status, metastasis time, tumor immune microenvironment, and biological effects. We also constructed a NETs-related gene metastasis signature(NRGMS) to assess the expression pattern of NETs in patients to predict metastatic recurrence in osteosarcoma patients. We screened for TOMM40 and FH associated with metastatic recurrence in osteosarcoma patients. Overall, this study constructs a predictive model for osteosarcoma metastasis of NETs-related genes, which is expected to provide new insights into the metastasis of osteosarcoma. [ABSTRACT FROM AUTHOR]

In this study, the intact Nanning stiff clay were subjected to cyclic wetting–drying under different axial constrain conditions. Experimental results showed that specimen presented vertical stress-dependent axial strain under one-dimensional condition, and gave varying axial stress responses under limited-axial swelling condition. At the first wetting stage, the swelling pressure extrapolated from the swelling strain–vertical stress relationship was found well comparable to that measured on the intact specimen hydrated under constant-volume condition. The proceeding wetting–drying cycles caused structural deterioration of the intact specimens, which differed under different constraint conditions, thus giving rise to different swelling behaviour of the soil. Under one-dimensional condition, the swelling deformation directly destroyed the diagenetic structure of the natural expansive stiff clay. Increasing the vertical stress helps prohibiting such destructive effect. While under limited-axial swelling condition, the specimen swelled to develop varying axial stress in response to hydration during each wetting–drying cycle. More interestingly, the developed axial stress presented a considerable decrease after it remained comparatively stable over three-consecutive wetting–drying cycles. By further analysing such evolving trend of the axial stress from the perspective of structural degradation, the de-structuration of expansive stiff clay under limited-axial swelling condition could evolve in forms of the desiccation- and hydration-induced cracks growth, diagenetic bonds breakdown and crack sealing during cyclic wetting–drying. Such degradation mechanism needs further verification and quantification by microstructural observations. [ABSTRACT FROM AUTHOR]

Purpose: To determine the independent predictive role of nasal obstruction in resistant hypertension (RH) in uncontrolled hypertensive patients with obstructive sleep apnea (OSA). Methods: This prospective cohort study comprised of 236 OSA patients with uncontrolled blood pressure (BP) using 1 or 2 classes of antihypertensive drugs visiting Sleep Medicine Center from April 2021 to March 2022. Information on demographic characteristics, comorbidities, BP control and classes of antihypertensive medication, sleep-related symptoms, Nasal Obstruction Symptom Evaluation (NOSE) Scale and sleep parameters was collected. RH incidence according to the BP control and classes of antihypertensive drugs data during the 5 month follow-up was collected. Results: After 5 month follow-up, 217 participants were included for final data analysis. Ninety-five subjects had nocturnal nasal obstruction with a higher proportion of RH (36.8% vs. 17.2%, p = 0.001) compared to those without nocturnal nasal obstruction. After adjustment for demographic characteristics, sleep-related symptoms and OSA severity, multinomial logistic regression models showed that nocturnal nasal obstruction (all ORs > 2.5, p < 0.05) or NOSE ≥ 8 (all ORs > 4.5, p < 0.05) was independently associated with a higher odds of RH. Nasal obstruction treatment improved NOSE score significantly, but did not reduce the incidence of RH significantly. Effective nasal obstruction treatment was associated with antihypertensive drugs reduction (OR 4.43; 95% CI 1.20–16.27). Conclusions: Nasal obstruction is an independent predictor of RH in uncontrolled hypertensive patients with OSA. In addition to the treatment of OSA, assessment and treatment of nasal obstruction should be considered in the management of uncontrolled hypertensive patients with OSA. [ABSTRACT FROM AUTHOR]

Adverse drug–drug interactions (DDIs) can severely damage the body. Thus, it is essential to accurately predict DDIs. DDIs are complex processes in which many factors can cause interactions. Rather than merely considering one or two of the factors, we design a two-pathway drug–drug interaction framework named TP-DDI that uses multimodal data for DDI prediction. TP-DDI effectively explores the combined effect of a topological structure-based pathway and a biomedical object similarity-based pathway to obtain multimodal drug representations. For the topology-based pathway, we focus on drug chemistry structures through the self-attention mechanism, which can capture hidden critical relationships, especially between pairs of atoms at remote topological distances. For the similarity-based pathway, our model can emphasize useful biomedical objects according to the channel weights. Finally, the fusion of multimodal data provides a holistic view of DDIs by learning the complementary features. On a real-world dataset, experiments show that TP-DDI can achieve better performance than the state-of-the-art models. Moreover, we can find the most critical substructures with certain interpretability in the newly predicted DDIs. [ABSTRACT FROM AUTHOR]

Purpose: It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates β3 adrenergic receptor (β3 AR). However, the effect of selective β3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. Methods: We generated a CIH-induced atherosclerosis model through exposing ApoE−/− mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5–21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective β3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. Results: The expression of β3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE−/− mice in CIH but not in normoxia. Mechanistically, mirabegron activated β3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, β3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. Conclusion: This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via β3 AR–mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH. [ABSTRACT FROM AUTHOR]

Single-cell RNA-seq technology provides an unprecedented opportunity to allow researchers to study the biological heterogeneity during cell differentiation and development with higher resolution. Although many computational methods have been proposed to infer cell lineages from single-cell RNA-seq data, constructing accurate cell trajectories remains a challenge. We develop a novel trajectory inference method-based probability distribution (TIPD) to describe the heterogeneity of cell population. TIPD combines signalling entropy and clustering results of the gene expression profile to describe the probability distributions of heterogeneous states in a cell population. It does not require external knowledge to determine the direction of the differentiation trajectories, so its application is not limited by the annotations of the data set. We also propose a new distance metric to measure the distance of the probability distributions of the identified heterogeneous states. On this distance matrix, a minimum spanning tree (MST) is built to reorganize the order of cell clusters. The constructed MST is calculated based on systems-level information, so it is consistent with the real biological process. We validated our method on four previously published single-cell RNA-seq data sets including the linear structure and branch structure. The results showed that TIPD successfully reconstructed the differentiation trajectories that are highly consistent with the known differentiation trajectories and outperformed the other four state-of-the-art methods under different assessment criteria. [ABSTRACT FROM AUTHOR]

Background: To investigate the severity of hypoxemia and prevalence of pulmonary hypertension (PHTN) in patients with the overlap syndrome (OS) of restrictive ventilatory defect (RVD) and sleep apnea (SA). Methods: Patients referred for both sleep test and spirometry for suspected SA and ventilatory disorders were recruited prospectively from January 2019 to January 2020. SA was determined by an apnea-hypopnea index ≥ 5/h; average oxygen saturation during sleep (meanSaO2) and percentage of total sleep time with saturation < 90% (T90) were calculated. RVD was diagnosed in the presence of forced expiratory volume in the first second/forced vital capacity (FVC) > 0.7 and FVC < 80% predicted value. PHTN was defined by tricuspid regurgitation peak velocity ≥ 3.4 m/s, documented by noninvasive transthoracic echocardiography. Results: Patients with OS had significantly lower meanSaO2 but higher T90 than subjects with isolated SA and isolated RVD. Patients with OS vs. those with isolated SA had higher odds of PHTN in multivariable analysis with age, sex, and body mass index adjusted for (OR 2.96, 95%CI 1.05–8.91, p = 0.040). Patients with meanSaO2 < 92% vs. meanSaO2 ≥ 92% had significantly higher odds of being diagnosed with PHTN (OR 5.40, 95%CI 2.01–15.7, p < 0.001). Similarly, T90 (≥ 4.5% versus < 4.5%) was also independently associated with the prevalence of PHTN (OR 7.21, 95%CI 2.54–23.67, p < 0.001). Conclusion: Patients with OS of RVD and SA had severe hypoxemia, which is associated with the prevalence of PHTN. Further investigation is needed to discern whether therapeutic strategies toward OS might mitigate PHTN in this cohort. Trial registration: Clinical Trial Registration No. ChiCTR1900027294 on 1 October 2019 [ABSTRACT FROM AUTHOR]

The electrode materials are traditionally loaded on the surface of the metal current collector by using of roll coating methods in sodium-ion batteries (SIBs). However, with the increase of the mass loading, the sodium storage performance of the cathodes deteriorates dramatically in the traditional casting process. In this work, we propose a novel strategy by applying electrospinning and airbrush-spraying technique to fabricate Na0.44MnO2-based paper (NMO-BP) electrodes. The results indicate that the NMO-BP electrodes show good electrochemical performance in terms of high areal capacities and good cycling stability with the loaded Na0.44MnO2 active material increasing from 2.6 to 10.4 mg cm−2. A high areal capacities of 1.10 mAh cm−2 is obtained in the NMO-BP electrodes with high areal loading (> 10 mg cm−2) for SIBs. This research provides a new method to explore cathode materials for sodium-ion battery with higher areal capacities. [ABSTRACT FROM AUTHOR]

Deciphering regulatory patterns of neural stem cell (NSC) differentiation with multiple stages is essential to understand NSC differentiation mechanisms. Recent single-cell transcriptome datasets became available at individual differentiation. However, a systematic and integrative analysis of multiple datasets at multiple temporal stages of NSC differentiation is lacking. In this study, we propose a new method integrating prior information to construct three gene regulatory networks at pair-wise stages of transcriptome and apply this method to investigate five NSC differentiation paths on four different single-cell transcriptome datasets. By constructing gene regulatory networks for each path, we delineate their regulatory patterns via differential topology and network diffusion analyses. We find 12 common differentially expressed genes among the five NSC differentiation paths, with one common regulatory pattern (Gsk3b_App_Cdk5) shared by all paths. The identified regulatory pattern, partly supported by previous experimental evidence, is essential to all differentiation paths, but it plays a different role in each path when regulating other genes. Together, our integrative analysis provides both common and specific regulatory mechanisms for each of the five NSC differentiation paths. [ABSTRACT FROM AUTHOR]

Tropical race 4 of Fusarium oxysporum f. sp. cubense (FocTR4) is seriously threatening the banana industry worldwide. Resistant genotypes are present in wild relatives of banana, but little is known about the genetic and molecular mechanisms driving resistance responses. In this work, through in-depth expression analysis, we compared the responses of the resistant wild relative Musa acuminata ssp. burmanicoides (WTB) with the susceptible banana cultivar "Brizilian" (CAV, as it belongs to the Cavendish subgroup) to FocTR4 infection. Our findings showed that 1196 defense-related genes in the resistant WTB were differentially expressed genes (DEGs); only 358 defense-related DEGs were detected in CAV. DEGs related to pattern recognition receptors (PRRs) and disease resistance (R genes) were found in both genotypes, indicating the onset of both basal and specific defenses to FocTR4. Genes associated with cell wall modification exhibited a more remarkable upregulation in WTB than in CAV and might be involved in resistance during penetration steps. Our data also suggested that the high resistance of WTB is quantitatively driven with larger numbers and higher expression levels of defense-related DEGs. Fine-tuning studies to understand the resistance responses of WTB at early stages should be conducted to better support banana breeding programs. Further investigations are also required to validate the role of key genes screened in this study. [ABSTRACT FROM AUTHOR]

Clustering analysis has been widely used in image segmentation, face recognition, protein identification, intrusion detection, document clustering and so on. Most of the previous clustering algorithms are not suitable for complex situations with manifold structure and large variations in density. Clustering by density core (DCore) turns out to be a very effective clustering method for complex structure. However, DCore must set too many parameters for better results, which often fails when the shape of data is complex and the density of data varies too much. Inspired by universal gravitation, we propose a novel clustering algorithm (called DCLRF) based on density core and local resultant force. In this algorithm, each data point is viewed as an object with a local resultant force (LRF) generated by its neighbors and a local measure named centrality is proposed based on LRF and natural neighbors. Firstly, we extract core points using the CE value. Then, we use the natural neighbor structure information of core points to get the final clustering results. Excluding the influence of noise, core points can well represent the structure of clusters. Therefore, DCLRF can obtain the optimal cluster numbers for the datasets which contain clusters of arbitrary shapes. Both synthetic datasets and real datasets are used for experiments to verify the efficiency and accuracy of the DCLRF. [ABSTRACT FROM AUTHOR]

As the second largest carbon flux in terrestrial ecosystems, the soil CO2 flux is closely related to the atmospheric CO2 concentration. The soil CO2 flux is the sum of biotic respiration and abiotic geochemical CO2 exchange; however, little is known about abiotic CO2 fluxes in arid areas. To investigate the relative contribution of abiotic and biotic soil CO2 fluxes over a diurnal course, the abiotic CO2 flux was distinguished by autoclaving sterilization in both saline and alkaline soils at an arid site in northwestern China. The results demonstrated that: (1) Over the diurnal course, the abiotic CO2 was a significant component of the soil CO2 flux in both saline and alkaline soil, which accounted for more than 56% of the diurnal soil CO2 flux. (2) There was a dramatic difference in the temperature response between biotic and abiotic CO2 fluxes: the response curves of biotic respiration were exponential in the saline soil and quadratic in the alkaline soil, while the abiotic CO2 flux was linearly correlated with soil temperature. They were of similar magnitude but with opposite signs: resulting in almost neutral carbon emissions on daily average. (3) Due to this covering up effect of the abiotic CO2 flux, biotic respiration was severely underestimated (directly measured soil CO2 flux was only one-seventh of the biotic CO2 flux in saline soil, and even an order of magnitude lower in alkaline soil). In addition, the soil CO2 flux masked the temperature-inhibition of biotic respiration in the alkaline soil, and veiled the differences in soil biological respiration between the saline and alkaline soils. Hence, the soil CO2 flux may not be an ideal representative of soil respiration in arid soil. Our study calls for a reappraisal of the definition of the soil CO2 flux and its temperature dependence in arid or saline/alkaline land. Further investigations of abiotic CO2 fluxes are needed to improve our understanding of arid land responses to global warming and to assist in identifying the underlying abiotic mechanisms. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder partly induced by dysregulation of different brain regions. Prefrontal cortex (PFC) dysregulation has been reported to associate with mental symptoms such as delusion, apathy, and depression in AD patients. However, the internal mechanisms have not yet been well-understood. This study aims to identify the potential therapeutic target genes and related pathways in PFC of AD. First, differential expression analyses were performed on transcriptome microarray of PFC between AD specimens and non-AD controls. Second, protein–protein interaction networks were constructed based on the identified differentially expressed genes to explore candidate therapeutic target genes. Finally, these candidate genes were validated through biological experiments. The enrichment analyses showed that the differentially expressed genes were significantly enriched in protein functions and pathways related to AD. Furthermore, the top ten hub genes in the protein–protein interaction network (ELAVL1, CUL3, MAPK6, FBXW11, YWHAE, YWHAZ, GRB2, CLTC, YWHAQ, and PDHA1) were proved to be directly or indirectly related to AD. Besides, six genes (PDHA1, CLTC, YWHAE, MAPK6, YWHAZ, and GRB2) of which were validated to significantly altered in AD mice by biological experiments. Importantly, the most significantly changed gene, PDHA1, was proposed for the first time that may be serve as a target gene in AD treatment. In summary, several genes and pathways that play critical roles in PFC of AD patients have been uncovered, which will provide novel insights on molecular targets for treatment and diagnostic biomarkers of AD. [ABSTRACT FROM AUTHOR]

The interaction of gastrodin with pepsin has been investigated by enzyme activity assay, fluorescence, UV-Visible, circular dichroism spectra, and molecular docking. The pepsin activity results suggest that gastrodin is an inhibitor of pepsin. The fluorescence experiments show that gastrodin can quench the fluorescence of pepsin via a static quenching process. The thermodynamic analysis suggests that hydrophobic interaction is the main force between pepsin and gastrodin. UV-Visible and circular dichroism spectra studies suggest that the binding of gastrodin leads to a loosening and unfolding of pepsin backbone with partial α-helix being transformed into β-sheet. All these experimental results have been validated by docking studies, which further show that besides hydrophobic interaction, hydrogen bond also help stabilize the gastrodin-pepsin complex. The results reveal the potential to develop the natural compound gastrodin for the treatment of diseases related to the excessive activity of pepsin. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinoma (GC) is one of the most common malignancies in the world and one of the most frequent causes of cancer-related death. Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. However, the mechanism and guiding significance of autophagy in the development and progression of GC have remained to be elucidated. This study aimed to explore the clinicopathological significances and prognostic values of autophagy-related proteins AMBRA1 and Beclin-1 in GC. Quantum dots based immunofluorescence histochemistry (QDs-IHC) was performed to observe the expression of AMBRA1 and Beclin-1 proteins in the tissue microarrays including 163 specimens of GC and 20 noncancerous gastric tissues. Simultaneously, AMBRA1 and Beclin-1 proteins were detected by Western blotting in the 10 fresh GC and corresponding normal gastric tissues. The results showed that the expression levels of both AMBRA1 and Beclin-1 proteins were higher in GC tissues than in noncancerous gastric tissues by QDs-IHC and Western blotting ( P<0.05). High AMBRA1 expression was detected in 90 of 163 (55.2%) GCs and high Beclin-1 expression was detected in 83 of 163 (50.9%) GCs. High AMBRA1 expression was closely related to depth of invasion, and lymph nodes metastasis ( P<0.05). High expression of Beclin-1 protein was correlated with tumor grade ( P<0.05). Positive correlation was observed between AMBRA1 and Beclin-1. Survival analysis indicated the high expression of AMBRA1 and Beclin- 1 was an independent factor in predicting poor overall survival (OS) of GC patients. These findings suggest the high expression of AMBRA1 and Beclin-1 proteins is significantly correlated with GC progression. High AMBRA1 and Beclin-1 expression heralds worse outcome of GC patients, suggesting a novel candidate prognostic marker and a therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Currently, IP mobility management solutions standardized by IETF rely on a centralized and static mobility approach, whereby a central mobility anchor manages mobility signaling and data traffic forwarding. All data traffic sent to a mobile node (MN) traverse the central mobility anchor regardless the current point of attachment of the MN in the Internet. Consequently, the packets follow a non-optimal path via the central mobility anchor which is typically located in the MN's home network, and result to increase in packet delivery latency. This paper discusses a distributed mobility management mechanism that releases the burden of the central mobility anchor by splitting the mobility management functions of the mobility anchor and co-locating the mobility routing function at the gateway of each sub-network. This mechanism optimizes the data path of the MN that has moved to visited networks, which reduces the packet delivery latency. Moreover, the mechanism is extended to achieve seamless handover when the MN moves between visited networks. Through simulation under NS-2, the performance of the packet delivery latency, handover delay and packet loss is studied and analyzed with respect to varying network load and increasing distance of the MN's home network from the visited networks. Simulation results show the improvement in packet delivery latency as compared to using non-optimized paths. Moreover, the results also verify the achievement of seamless handover when an MN moves between visited networks. [ABSTRACT FROM AUTHOR]

Debris flow occurs frequently (ten events on average per year) and displays a great variety of properties in the Jiangjia Gully (JJG) in southwest China. We find that the material of debris flow satisfies a universal grain size distribution (GSD) of P ( D) = CDexp(− D/ D), and the parameters μ and D are closely related to the dynamical properties such as flow density, velocity, and discharge. A small μ implies a small porosity and possible high excess pore pressure in flow, reflecting high mobility and capacity of transportation, and a large D means a wide range of grain composition and hence a high grain concentration. A debris flow always achieves a state of certain mobility and density that can be well described by μ and D, and the parameters impose power law constraints on the fluctuations of debris flow surges. An upper limit of unit-width discharge is estimated as Q = 1.25 D. Variation of GSD parameters also describes material exchanges between debris flow and streambed sediment. Intense incision or deposition occurs when remarkable difference of grain composition exists. As the GSD is satisfied universally, the results derived from JJG are expected to be applicable for evaluating the properties and peak discharge of a potential debris flow in other conditions. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of biodegradable multifunctional group-terminated copolymers is explored, by which a series of novel biodegradable tetra-amino-terminated PLGA telechelic copolymers are synthesized for the first time. The composition, structure, and thermal property of the telechelic copolymer were characterized by FTIR, NMR, GPC, and MDSC. The results show that by careful selection of the synthesis parameters, tetra-amino-terminated PLGA telechelic copolymer with desired molecular weight and glass transition temperature can be prepared. This versatile synthetic platform can provide a large family of biodegradable, tetra-amino-terminated telechelic copolymers with tunable physiochemical and biological properties useful for the preparation of network biodegradable polyester elastomer with tailorable properties. [ABSTRACT FROM AUTHOR]

Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine the anti-remodeling effect of intravenous MSCs (VMSCs) and intratracheal MSCs (TMSCs) in rats with PH, and the underlying mechanisms. MSCs were isolated from rat bone marrow and cultured. PH was induced in rats by intraperitoneal injection of MCT. One week after MCT administration, the rats were divided into 3 groups in terms of different treatments: VMSCs group (intravenous injection of MSCs), TMSCs group (intratracheal injection of MSCs), PH group (no treatment given). Those receiving saline instead of MCT served as negative control (control group). Pulmonary arterial structure was pathologically observed, pulmonary arterial dynamics measured, and remodeling-associated cytokines Smad2 and Smad3 detected in the lungs, three weeks after MCT injection. The results showed that PH group versus control group had higher pulmonary arterial pressure (PAP) and wall thickness index (WTI) 21 days after MCT treatment. The expression of phosphorylated (p)-Smad2 and the ratio of p-Smad2/Smad2 were much higher in PH group than in control group. Fluorescence-labeled MSCs were extensively distributed in rats' lungs in VMSCs and TMSCs groups 3 and 14 days after transplantation, but not found in the media of the pulmonary artery. WTI and PAP were significantly lower in both VMSCs and TMSCs groups than in PH group three weeks after MCT injection. The p-Smad2 expression and the ratio of p-Smad2/Smad2 were obviously reduced in VMSCs and TMSCs groups as compared with those in PH group. In conclusion, both intravenous and intratracheal transplantation of MSCs can attenuate PAP and pulmonary artery remodeling in MCT-induced PH rats, which may be associated with the early suppression of Smad2 phosphorylation via paracrine pathways. [ABSTRACT FROM AUTHOR]

Real-time reverse transcriptase (RT)-PCR using SYBR GreenI was applied to quantify sucrose phosphate synthase (SPS) mRNA expression at different storage days during the natural ripening (with no treatment), inhibited ripening with ethylene absorbent and accelerated ripening by treatment with propylene of banana fruit. The results showed that expression level of SPS mRNA were significantly different between 3 kinds of ripening fruit. Expression of SPS mRNA in fruit treated with propylene was dramatically promoted, the peak of SPS mRNA expression in these fruits appeared 16 days earlier than that in fruit with natural ripening. On the contrary, when fruit applied with ethylene absorbent, SPS mRNA expression was remarkably inhibited, the amount of SPS mRNA expression were significantly lower than that in naturally ripened fruit. These results indicated that the expression level of SPS mRNA of banana fruit can be impacted by regulating ethylene evolution, and that close relationships may exist between SPS mRNA expression and SPS activity, fruit softening, respiration rate, and ethylene production during ripening of banana fruit. [ABSTRACT FROM AUTHOR]

Cytoscape is one of the most popular platforms for biomolecular networks research. However Cytoscape cannot display biomolecular names according to their accession identifiers in different databases. A plugin named Ai2NU is designed and implemented in this paper. It can make biomolecular names displayed automatically in biomolecular networks graphs in Cytoscape by constructing a local dictionary. It is convenient for researchers to recognize biomolecules and enhance the research efficiency. [ABSTRACT FROM AUTHOR]

Alpha-synuclein plays an important role in Parkinson’s disease (PD). The current study of alpha-synuclein mainly concentrates at the gene level. However, it is found that the study at the protein level has special significance. Meanwhile, there is free information on the Internet, such as databases and algorithms of protein-protein interactions (PPIs). In this paper, a novel method which integrates distributed heterogeneous data sources and algorithms to predict PPIs for alphasynuclein in silico is proposed. The PPIs generated by the method take advantage of various experimental data, and indicate new information about PPIs for alpha-synuclein. In the end of this paper, the result illustrates that the method is practical. It is hoped that the prediction result obtained by this method can provide guidance for biological experiments of PPIs for alpha-synuclein to reveal possible mechanisms of PD. [ABSTRACT FROM AUTHOR]

The article introduces various reports published within the issue including "MobiSoC: A Middleware for Mobile Social Computing Applications," "Recoverable Class Loaders for a Fast Restart of Java Applications," and "Privacy from Promises to Protection-Privacy Guaranteeing Execution Container."

Cassava (Manihot esculenta) is a major staple food, animal feed and energy crop in the tropics and subtropics. It is one of the most drought-tolerant crops, however, the mechanisms of cassava drought tolerance remain unclear. Abscisic acid (ABA)-responsive element (ABRE)-binding factors (ABFs) are transcription factors that regulate expression of target genes involved in plant tolerance to drought, high salinity, and osmotic stress by binding ABRE cis-elements in the promoter regions of these genes. However, there is little information about ABF genes in cassava. A comprehensive analysis of Manihot esculenta ABFs (MeABFs) described the phylogeny, genome location, cis-acting elements, expression profiles, and regulatory relationship between these factors and Manihot esculenta betaine aldehyde dehydrogenase genes (MeBADHs). Here we conducted genome-wide searches and subsequent molecular cloning to identify seven MeABFs that are distributed unevenly across six chromosomes in cassava. These MeABFs can be clustered into three groups according to their phylogenetic relationships to their Arabidopsis (Arabidopsis thaliana) counterparts. Analysis of the 5′-upstream region of MeABFs revealed putative cis-acting elements related to hormone signaling, stress, light, and circadian clock. MeABF expression profiles displayed clear differences among leaf, stem, root, and tuberous root tissues under non-stress and drought, osmotic, or salt stress conditions. Drought stress in cassava leaves and roots, osmotic stress in tuberous roots, and salt stress in stems induced expression of the highest number of MeABFs showing significantly elevated expression. The glycine betaine (GB) content of cassava leaves also was elevated after drought, osmotic, or salt stress treatments. BADH1 is involved in GB synthesis. We show that MeBADH1 promoter sequences contained ABREs and that MeBADH1 expression correlated with MeABF expression profiles in cassava leaves after the three stress treatments. Taken together, these results suggest that in response to various dehydration stresses, MeABFs in cassava may activate transcriptional expression of MeBADH1 by binding the MeBADH1 promoter that in turn promotes GB biosynthesis and accumulation via an increase in MeBADH1 gene expression levels and MeBADH1 enzymatic activity. These responses protect cells against dehydration stresses by preserving an osmotic balance that enhances cassava tolerance to dehydration stresses. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a movement disorder due to the loss of dopaminergic (DA) neurons in the substantia nigra. Alpha-synuclein phosphorylation and α-synuclein inclusion (Lewy body) become a main contributor, but little is known about their formation mechanism. Here we used protein expression profiling of PD to construct a model of their signalling network from drsophila to human and nominate major nodes that regulate PD development. We found in this network that LK6, a serine/threonine protein kinase, plays a key role in promoting α-synuclein Ser129 phosphorylation by identification of LK6 knockout and overexpression. In vivo test was further confirmed that LK6 indeed enhances α-synuclein phosphorylation, accelerates the death of dopaminergic neurons, reduces the climbing ability and shortens the the life span of drosophila. Further, MAP kinase-interacting kinase 2a (Mnk2a), a human homolog of LK6, also been shown to make α-synuclein phosphorylation and leads to α-synuclein inclusion formation. On the mechanism, the phosphorylation mediated by LK6 and Mnk2a is controlled through ERK signal pathway by phorbolmyristate acetate (PMA) avtivation and PD98059 inhibition. Our findings establish pivotal role of Lk6 and Mnk2a in unprecedented signalling networks, may lead to new therapies preventing α-synuclein inclusion formation and neurodegeneration. [ABSTRACT FROM AUTHOR]

Species competitive abilities and their distributions are closely related to functional traits such as biomass allocation patterns. When we consider how nutrient supply affects competitive abilities, quantifying the apparent and true plasticity in functional traits is important because the allometric relationships among traits are universal in plants. We propose to integrate the notion of allometry and the classical reaction norm into a composite theoretical framework that quantifies the apparent and true plasticity. Combining the framework with a meta-analysis, a series of field surveys and a competition experiment, we aimed to determine the causes of the dune/interdune distribution patterns of two Haloxylon species in the Gurbantonggut Desert. We found that (1) the biomass allocation patterns of both Haloxylon species in responses to environmental conditions were apparent rather than true plasticity and (2) the allometric allocation patterns affected the plants' competition for soil nutrient supply. A key implication of our results is that the apparent plasticity in functional traits of plants determines their response to environmental change. Without identifying the apparent and true plasticity, we would substantially overestimate the magnitude, duration and even the direction of plant responses in functional traits to climate change. [ABSTRACT FROM AUTHOR]