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1.
Cancer Commun (Lond) ; 39(1): 81, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796105

RESUMO

BACKGROUND: High-grade glioma (HGG) is a fatal human cancer. Bortezomib, a proteasome inhibitor, has been approved for the treatment of multiple myeloma but its use in glioma awaits further investigation. This study aimed to explore the chemotherapeutic effect and the underlying mechanism of bortezomib on gliomas. METHODS: U251 and U87 cell viability and proliferation were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, tumor cell spheroid growth, and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry. Temozolomide (TMZ)-insensitive cell lines were induced by long-term TMZ treatment, and cells with stem cell characteristics were enriched with stem cell culture medium. The mRNA levels of interested genes were measured via reverse transcription-quantitative polymerase chain reaction, and protein levels were determined via Western blotting/immunofluorescent staining in cell lines and immunohistochemical staining in paraffin-embedded sections. Via inoculating U87 cells subcutaneously, glioma xenograft models in nude mice were established for drug experiments. Patient survival data were analyzed using the Kaplan-Meier method. RESULTS: Bortezomib inhibited the viability and proliferation of U251 and U87 cells in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest. Bortezomib also significantly inhibited the spheroid growth, colony formation, and stem-like cell proliferation of U251 and U87 cells. When administrated in combination, bortezomib showed synergistic effect with TMZ in vitro and sensitized glioma to TMZ treatment both in vitro and in vivo. Bortezomib reduced both the mRNA and protein levels of Forkhead Box M1 (FOXM1) and its target gene Survivin. The FOXM1-Survivin axis was markedly up-regulated in established TMZ-insensitive glioma cell lines and HGG patients. Expression levels of FOXM1 and Survivin were positively correlated with each other and both related to poor prognosis in glioma patients. CONCLUSIONS: Bortezomib was found to inhibit glioma growth and improved TMZ chemotherapy efficacy, probably via down-regulating the FOXM1-Survivin axis. Bortezomib might be a promising agent for treating malignant glioma, alone or in combination with TMZ.

2.
Comput Biol Chem ; 83: 107146, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707129

RESUMO

Protein-protein interaction (PPI) extraction from published scientific literature provides additional support for precision medicine efforts. Meanwhile, knowledge bases (KBs) contain huge amounts of structured information of protein entities and their relations, which can be encoded in entity and relation embeddings to help PPI extraction. However, the prior knowledge of protein-protein pairs must be selectively used so that it is suitable for different contexts. This paper proposes a Knowledge Selection Model (KSM) to fuse the selected prior knowledge and context information for PPI extraction. Firstly, two Transformers encode the context sequence of a protein pair according to each protein embedding, respectively. Then, the two outputs are fed to a mutual attention to capture the important context features towards the protein pair. Next, the context features are used to distill the relation embedding by a knowledge selector. Finally, the selected relation embedding and the context features are concatenated for PPI extraction. Experiments on the BioCreative VI PPI dataset show that KSM achieves a new state-of-the-art performance (38.08 % F1-score) by adding knowledge selection.

3.
Anesth Analg ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31702696

RESUMO

BACKGROUND: It is unclear whether transfusion of platelets or fresh frozen plasma, in addition to red blood cells, is associated with an increased risk of mortality and infection after cardiac surgery. METHODS: Patients who underwent valve surgery and/or coronary artery bypass grafting from January 1, 2011 to June 30, 2017 and September 1, 2013 to June 30, 2017 at 2 centers performing cardiac surgery were included in this retrospective study. After stratifying patients based on propensity score matching, we compared rates of mortality and infection between patients who transfused red blood cells, fresh frozen plasma, or platelets with those who did not receive such transfusions. We also compared outcomes between patients who received any of the 3 blood products and patients who received no transfusions at all. Multivariable logistic regression was used to assess associations between transfusion and outcomes. RESULTS: Of 8238 patients in this study, 109 (1.3%) died, 812 (9.9%) experienced infection, and 4937 (59.9%) received at least 1 type of blood product. Transfusion of any blood type was associated with higher rates of mortality (2.0% vs 0.18%; P < .01) and infection (13.3% vs 4.8%; P < .01). Each of the 3 blood products was independently associated with an increase in mortality per unit transfused (red blood cells, odds ratio 1.18, 95% confidence interval [CI], 1.14-1.22; fresh frozen plasma, odds ratio 1.24, 95% CI, 1.18-1.30; platelets, odds ratio 1.12, 95% CI, 1.07-1.18). Transfusing 3 units of any of the 3 blood products was associated with a dose-dependent increase in the incidence of mortality (odds ratio 1.88, 95% CI, 1.70-2.08) and infection (odds ratio 1.50, 95% CI, 1.43-1.57). CONCLUSIONS: Transfusion of red blood cells, fresh frozen plasma, or platelets is an independent risk factor of mortality and infection, and combination of the 3 blood products is associated with adverse outcomes after cardiac surgery in a dose-dependent manner.

4.
Cell Biol Toxicol ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768838

RESUMO

Inflammation reaction mediated by NLRP3 inflammasome and Nrf2-related oxidative stress are vital participants in the development of diabetic nephropathy (DN) and closely associated to kidney fibrosis. Nrf2, a known antioxidative transcription factor, has been reported to activate NLRP3 inflammasome through its downstream factors (HO-1, NQO1, etc.) recently. AB38b is a newly synthesized biphenyl diester derivative with a Nrf2 activation property. This research aims to evaluate the renal protective effects of AB-38b and to elucidate the anti-inflammation mechanisms involved. Type 2 diabetic mice induced by high fat diet with streptozocin (STZ) and high glucose-cultured mouse glomerular mesangial cells (GMCs) were used in current study. Results showed that administration of AB-38b improved the kidney function while attenuated renal fibrosis progression in diabetic mice together with reducing the extracellular matrix (ECM) accumulation of GMCs cultured in high glucose. Mechanistically, treatment with AB-38b significantly decreased the high level of NLRP3 inflammasome in diabetic condition by inhibiting the ROS/TXNIP/NLRP3 signaling pathway. And meanwhile, AB-38b treatment effectively improved Nrf2 signaling during diabetic condition. Furthermore, knocking down the gene expression of Nrf2 by siRNA in GMCs abolished the inhibition effect of AB-38b on NLRP3 inflammasome activation and ECM accumulation. Taken together, our data suggest that AB-38b was able to improve the renal function of diabetic mice, and the NLRP3 inflammasome inhibition effect of AB-38b was responsible for the renal protective effect. Further exploration indicate that Nrf2 plays pivotal role in AB-38b's attenuation of DN progression through inhibiting NLRP3 inflammasome activation.

5.
Acta Pharmacol Sin ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645661

RESUMO

Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, ß-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mM)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg-1· d-1, ig) or a positive control drug resveratrol (40 mg· kg-1· d-1, ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5-10 µM) or resveratrol (10 µM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31634139

RESUMO

Brain imaging genetics studies the genetic basis of brain structures and functionalities via integrating genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). In this area, both multi-task learning (MTL) and sparse canonical correlation analysis (SCCA) methods are widely used since they are superior to those independent and pairwise univariate analysis. MTL methods generally incorporate a few of QTs and could not select features from multiple QTs; while SCCA methods typically employ one modality of QTs to study its association with SNPs. Both MTL and SCCA are computational expensive as the number of SNPs increases. In this paper, we propose a novel multi-task SCCA (MTSCCA) method to identify bi-multivariate associations between SNPs and multi-modal imaging QTs. MTSCCA could make use of the complementary information carried by different imaging modalities. MTSCCA enforces sparsity at the group level via the G2,1-norm, and jointly selects features across multiple tasks for SNPs and QTs via the L2,1-norm. A fast optimization algorithm is proposed using the grouping information of SNPs. Compared with conventional SCCA methods, MTSCCA obtains better correlation coefficients and canonical weights patterns. In addition, MTSCCA runs very fast and easy-to-implement, indicating its potential power in genome-wide brain-wide imaging genetics.

7.
ACS Appl Mater Interfaces ; 11(44): 41258-41266, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31603640

RESUMO

The nitrogen coordinated single cobalt atoms embedded in carbon matrix, i.e., Co/N/C material, is cost-efficient and free from iron-ion induced Fenton reagent, which has been thus considered as a promising candidate to replace the well-accepted Pt-based and Fe/N/C materials for oxygen reduction reaction (ORR). Recently, the pyrolysis of metal-organic framework (MOF) precursors has been investigated to achieve well-defined Co/N/C catalysts with high ORR activity. However, the relationships among the composition/structure of MOF precursor, the derived catalysts, and ORR performance have been rarely touched in specialty, while the regulations to achieve single-atom Co/N/C catalysts derived from MOF are confusing. Herein, we engineer several Co-doped MOF (zeolitic imidazolate frameworks, to be specific) precursors with different compositions and structures by tuning synthesis protocols (e.g., ratios, cobalt sources, and reaction time) and investigate the derived catalysts and their ORR properties. The regulations to single-atom Co/N/C are revealed in this work. The superior ORR activity and durability of the optimized Co/N/C catalysts are revealed and attributed to the well-defined Co-Nx moieties and their stable nanostructures.

8.
ACS Appl Mater Interfaces ; 11(45): 42744-42750, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638769

RESUMO

The rapid development of both wearable and implantable biofuel cells has triggered more and more attention on the lactate biofuel cell. The novel lactate/oxygen biofuel cell (L/O-BFC) with the direct electron transfer (DET)-type lactate oxidase (LOx) anode and the platinum group metal (PGM)-free Fe-N-C cathode is designed and constructed in this paper. In such a reasonable design, the surface-controlled direct two-electron electrochemical reaction of the lactate oxidase was determined by cyclic voltammetry (CV) on the carbon nanotube (CNT) modified electrode with favorable high electrochemical active surface area and electronic conductivity. Additionally, the biosensor based on DET-type LOx modified electrode impressively presented linear response to lactate with different concentrations from 0.000 mM to 12.300 mM. In particular, the apparent Michealis-constant (KMapp) calculated as 0.140 mM clearly indicates that LOx on CNT has strong affinity to the substrate lactate. Meanwhile, 4e- transfer oxygen reduction reaction (ORR) was proven to take place on the Fe-N-C catalysts inthe 0.1 M PBS system, indicating the advantage by using the Fe-N-C catalysts at the cathode of L/O-BFC. Last but not least, the L/O-BFC with the direct electron transfer (DET)-type lactate oxidase(LOx) anode and the Fe-N-C cathode produced an superior open circuit potential (OCP) of 0.264 V and a maximum output power density (OPD) of 24.430 µW cm-2 in O2 saturated 95.020 mM lactate solution. The above results will not only bring about significant interest in developing a DET-type biofuel cell, but also offer guiding direction to explore novel catalyst materials for the biofuel cell. This work enriches the research content and may push developments of the implantable and wearable biofuel cell forward.

9.
Sci Rep ; 9(1): 13069, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506454

RESUMO

Platelet-leukocyte aggregate (PLA) is implicated in the etiology of both vascular lesions and cardiovascular events. This prospective cohort study aimed to examine the prognostic value of PLA for major adverse cardiac and cerebrovascular events (MACCE) and perioperative adverse events (AEs) in patients with rheumatic heart disease undergoing surgical intervention by Cox proportional hazard regression and logistic regression. A total of 244 patients were included, of whom 7 were lost to follow-up. Among the analyzed 237 subjects who completed 3-year follow-up, 30 experienced MACCE and 38 experienced perioperative AEs. Preoperative PLA was higher in subjects who developed MACCE (13.32%) than in those who did not (8.69%, p = 0.040). In multivariate regression, elevated PLA was associated with increased MACCE (hazard ratio 1.51 for each quartile, 95% CI 1.07-2.13; p = 0.020), and perioperative AEs (odds ratio 1.61, 95% CI 1.14-2.26; p = 0.007). The optimal PLA cut-off for predicting MACCE was 6.8%. Subjects with PLA > 6.8% had a higher prevalence of MACCE (17.1% vs. 5.5%, p = 0.009) and perioperative AEs (19.9% vs. 8.6%, p = 0.018). Kaplan-Meier analysis showed shorter MACCE-free survival in patients with PLA > 6.8% (p = 0.007, log rank). Elevated preoperative PLA is associated with increased MACCE and perioperative AEs in patients with rheumatic valve disease undergoing surgical intervention.

10.
Bioinformatics ; 35(14): i474-i483, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31510645

RESUMO

MOTIVATION: Identifying the genetic basis of the brain structure, function and disorder by using the imaging quantitative traits (QTs) as endophenotypes is an important task in brain science. Brain QTs often change over time while the disorder progresses and thus understanding how the genetic factors play roles on the progressive brain QT changes is of great importance and meaning. Most existing imaging genetics methods only analyze the baseline neuroimaging data, and thus those longitudinal imaging data across multiple time points containing important disease progression information are omitted. RESULTS: We propose a novel temporal imaging genetic model which performs the multi-task sparse canonical correlation analysis (T-MTSCCA). Our model uses longitudinal neuroimaging data to uncover that how single nucleotide polymorphisms (SNPs) play roles on affecting brain QTs over the time. Incorporating the relationship of the longitudinal imaging data and that within SNPs, T-MTSCCA could identify a trajectory of progressive imaging genetic patterns over the time. We propose an efficient algorithm to solve the problem and show its convergence. We evaluate T-MTSCCA on 408 subjects from the Alzheimer's Disease Neuroimaging Initiative database with longitudinal magnetic resonance imaging data and genetic data available. The experimental results show that T-MTSCCA performs either better than or equally to the state-of-the-art methods. In particular, T-MTSCCA could identify higher canonical correlation coefficients and capture clearer canonical weight patterns. This suggests that T-MTSCCA identifies time-consistent and time-dependent SNPs and imaging QTs, which further help understand the genetic basis of the brain QT changes over the time during the disease progression. AVAILABILITY AND IMPLEMENTATION: The software and simulation data are publicly available at https://github.com/dulei323/TMTSCCA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

11.
Opt Express ; 27(15): 21843-21855, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510254

RESUMO

We study the controllable optical response in a three-mode optomechanical system comprised of two indirectly coupled cavity modes and an intermediate mechanical mode. The two cavity modes are assumed to have different frequencies and driven by two control fields on the red and blue sidebands, respectively. When the system is perturbed by two probe fields satisfying the specific matching condition, a series of intriguing phenomena can be observed by adjusting phases and amplitudes of the control fields, such as absorption-amplification switching, ultra-narrow response windows, frequency-independent perfect reflection, and ultralong optical group delay. We also compare our system with conventional optomechanical systems to highlight its distinct features. Our results may have potential applications in optical communication and quantum information processing.

13.
Aging Cell ; 18(6): e13024, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31389140

RESUMO

Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long-acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat-to-mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.

14.
Phytother Res ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452288

RESUMO

Multiphase pathological processes involve in Type 2 diabetes (T2DM)-induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM-induced NAFLD were investigated. T2DM-induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM-induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM-induced production of interleukin 1 beta, interleukin 6, and TNF-α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM-induced NAFLD. In high D-glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G-protein-coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM-induced NAFLD.

15.
Ying Yong Sheng Tai Xue Bao ; 30(7): 2345-2351, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31418238

RESUMO

Clubroot, caused by the soil-borne obligate pathogen Plasmodiophora brassicae, is one of the most severe disease in cruciferous crops. Previous studies showed that when oilseed rape was planted after soybean (namely soybean-oilseed rotation), the incidence and severity of clubroot of oilseed rape could be significantly reduced, compared with that with oilseed rape-oilseed rape conti-nuous cropping. Therefore, the soybean-oilseed rape rotation is a good way to suppress clubroot of oilseed rape. In this study, we compared the rhizosphere microbiome of soybean and oilseed rape rhizosphere soil collected from the field by 16S rRNA (for identification of prokaryotes) and the internal transcribed spacer (ITS) (for identification of fungi) sequencing. The results showed that both soybean and oilseed rape rhizosphere soils had Proteobacteria, Bacteroidetes, Acidobacteria, Actinobacteria, Ascomycota, Zygomycota, Basidiomycota and Chytridiomycota. Many microbial genera (e.g., Flavobacterium, Sphingomonas, Bacillus, Streptomyces, Pseudomonas, Trichoderma and Coniothyrium) with activities of biological control and plant growth promotion were more abundant in soybean rhizosphere soil than in the oilseed rape rhizosphere soil. The abundance of plant pathogenic bacteria and fungi was higher in the oilseed rape rhizosphere soil than in the soybean rhizosphere soil. Moreover, the soybean rhizosphere soil was enriched with Rhizobium, Bradyrhizobium (both for nitrogen fixation), and arbuscular mycorrhizal fungus (Glomus). These results indicated that soybean rhizosphere soil could promote the growth and proliferation of beneficial microorga-nisms, but inhibit that of plant pathogens. Our results provide evidence for explanation of the effectiveness of soybean-oilseed rape rotation to control clubroot of oilseed rape and provide potential bio-control resources for clubroot prevention.


Assuntos
Microbiota , Rizosfera , Microbiologia do Solo , Brassica rapa/crescimento & desenvolvimento , Brassica rapa/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , RNA Ribossômico 16S , Soja/crescimento & desenvolvimento , Soja/microbiologia
16.
Acta Pharmacol Sin ; 40(12): 1555-1567, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31235817

RESUMO

Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the potential mechanisms of renal fibrosis, which promotes the development of diabetic nephropathy (DN). However, the molecular mechanisms of EMT remain largely unknown. Tuberous sclerosis proteins TSC1 and TSC2 are key integrators of growth factor signaling, and the loss of TSC1 or TSC2 function leads to a spectrum of diseases that underlie abnormalities in cell growth, proliferation, differentiation, and migration. In this study, we investigated the effects of TSC1 on high glucose (HG)-induced EMT of human proximal tubular epithelial HK-2 cells in vitro and renal fibrosis in TSC1-/- and db/db mice. We found that the exposure of HK-2 cells to HG (30 mM) time-dependently decreased TSC1 expression, increased the phosphorylation of mTORC1, P70S6K, and 4E-BP-1, and promoted cell migration, resulting in EMT. Transfection of the cells with TSC1 mimic significantly ameliorated HG-induced EMT of HK-2 cells. The tubules-specific TSC1 knockout mice (TSC1-/-) displayed a significant decline in renal function. TSC1-/- mice, similar to db/db mice, showed greatly activated mTORC1 signaling and EMT process in the renal cortex and exacerbated renal fibrosis. Overexpression of TSC1 through LV-TSC1 transfection significantly alleviated the progression of EMT and renal fibrosis in the renal cortex of db/db mice. Taken together, our results suggest that TSC1 plays a key role in mediating HG-induced EMT, and inhibition of TSC1-regulated mTORC1 signaling may be a potential approach to prevent renal fibrosis in DN.

17.
J Biomed Inform ; 96: 103234, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202937

RESUMO

Protein-protein interaction (PPI) extraction from published scientific literature provides additional support for precision medicine efforts. However, many of the current PPI extraction methods need extensive feature engineering and cannot make full use of the prior knowledge in knowledge bases (KBs). KBs contain huge amounts of structured information about entities and relationships, therefore play a pivotal role in PPI extraction. This paper proposes a knowledge-aware attention network (KAN) to fuse prior knowledge about protein-protein pairs and context information for PPI extraction. The proposed model first adopts a diagonal-disabled multi-head attention mechanism to encode context sequence along with knowledge representations learned from KBs. Then a novel multi-dimensional attention mechanism is used to select the features that can best describe the encoded context. Experiment results on the BioCreative VI PPI dataset show that the proposed approach could acquire knowledge-aware dependencies between different words in a sequence and lead to a new state-of-the-art performance.

18.
ISA Trans ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31151750

RESUMO

Towing is a critical process to deploy a cylindrical drilling platform. However, the towing process faces a great variety of risks from a complex nautical environment, the dynamics in towing and maneuvering, to unexpected events. Therefore, safely navigating the towing system following a planned route to a target sea area is essential. To tackle the time-varying disturbances induced by wind, current and system parametric uncertainties, a path following control method for a towing system of cylindrical drilling platform is designed based on linear active disturbance rejection control. By utilizing Maneuvering Modeling Group model as well as a catenary model, we develop a three degree-of-freedom dynamic mathematical model of the towing system under external environmental disturbances and internal uncertainties. Furthermore, we design a linear active disturbance rejection control path following controller for real-time tracking error correction based on a guidance method combining cross-track error and parallax. Finally, the path following performance of the towing system is evaluated in a simulation environment under various disturbances and internal uncertainties, where the corresponding tracking error is analyzed. The results show that the linear active disturbance rejection control performs well under both the external disturbance and inherent uncertainties, and better satisfy the tracking performance criteria than a traditional proportional-integral-derivative controller.

19.
Proc Natl Acad Sci U S A ; 116(27): 13305-13310, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31209052

RESUMO

Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and ß-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal ß-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.

20.
PLoS One ; 14(5): e0216562, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075129

RESUMO

BACKGROUND: Acute pancreatitis (AP) is associated with high complications. Early, reliable prediction of mortality may improve patient management. METHODS: We retrospectively reviewed medical records of 1,599 patients with AP treated at a single large hospital in southwest China. Models to predict mortality were derived from a subset of 1,062 patients (development dataset), and the models were then validated in the remaining 537 patients (validation dataset). Independent risk factors and prediction models for mortality were identified using logistic regression. RESULTS: A total of 33 patients in the development dataset and 13 in the validation dataset died during hospitalization. Independent risk factors for mortality were found to be plasma urea levels, glucose levels and platelet counts at admission; as well as peak urea levels, leukocyte counts and use of invasive ventilation during hospitalization. Based on the development dataset, a mortality prediction model based only on urea level at admission gave an area under the curve (AUC) of 0.81, which did not significantly improve by incorporating glucose level or platelet count at admission. Significantly better was a model taking into account three in-hospital parameters: peak urea level, leukocyte count and use of invasive ventilation (AUC 0.97). CONCLUSIONS: While mortality of AP patients can be predicted reasonably well based only on urea values at admission, predictions are more reliable when they take into account in-hospital data on peak urea level, leukocyte count and use of invasive ventilation.

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