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1.
Artigo em Inglês | MEDLINE | ID: mdl-32406228

RESUMO

Polycyclic aromatic hydrocarbons such as perylene, pyrene, and their derivatives are highly emissive fluorophores in solution. However, the practical applications of these materials in the field of molecular electronic and light emitting devices are often hindered by self-quenching effects due to the formation of non-fluorescent aggregates in concentrated solutions or in the solid state. Herein, we demonstrate that aggregation caused quenching of perylenes can be minimalized by molecular incorporation into metal-organic frameworks (MOFs). This study utilized a stable Zr6 cluster-based MOF, UiO-67, as a matrix. Linear linkers containing the photo-responsive moieties were designed and incorporated into the parent UiO-67 scaffold through the partially replacement of the non-fluorescent linkers of a similar length, forming mixed-linker MOFs. The average distance between perylene moieties was tuned by changing the linker ratios, thus controlling the fluorescence intensity, emission wavelength, and quantum yield. Molecular modeling was further adopted to correlate the number of isolated perylene linkers within the framework to the ratio between the two linkers, therefore rationalizing the change in the observed fluorescent properties. Taking advantage of the tunable fluorescence, inherent porosity, and high chemical stability of this MOF platform, it was applied as a fluorescent sensor for oxygen detection in the gas phase, a model reaction, showing fast response and good recyclability.

2.
IEEE Trans Cybern ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32396119

RESUMO

This article proposes an adaptive finite-time tracking control based on fuzzy-logic systems (FLSs) for an uncertain nonstrict nonlinear multi-input-multi-output (MIMO) full-state-constrained system with the coupled uncertain dead-zone input. By using three kinds of FLSs: the uncertain system, the uncertain dead zone, and the uncertain input transfer inverse matrix are approximated using the system function FLS, dead-zone FLS, and input transfer inverse matrix FLS, respectively. After defining the barrier Lyapunov function, the fuzzy-based adaptive tracking controllers are designed, and the fuzzy weights are updated through the proposed adaptive laws. Then, based on the extended finite-time convergence theorem, with the design parameters chosen properly, the target uncertain nonlinear system is guaranteed to be semiglobal practical finite-time stable (SGPFS); and the full-state constraints are not violated while avoiding the effects of the dead zones. Furthermore, a simulation is presented to verify the validity of the proposed algorithm.

3.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(2): 147-151, 2020 Feb 29.
Artigo em Chinês | MEDLINE | ID: mdl-32376532

RESUMO

The SARS-CoV-2 epidemic starting in Wuhan in December, 2019 has spread rapidly throughout the nation. The control measures to contain the epidemic also produced influences on the transport and treatment process of patients with acute myocardial infarction (AMI), and adjustments in the management of the patients need to be made at this particular time. AMI is characterized by an acute onset with potentially fatal consequence, a short optimal treatment window, and frequent complications including respiratory infections and respiratory and circulatory failure, for which active on-site treatment is essential. To standardize the management and facilitate the diagnosis and treatment, we formulated the guidelines for the procedures and strategies for the diagnosis and treatment of AMI, which highlight 5 Key Principles, namely Nearby treatment, Safety protection, Priority of thrombolysis, Transport to designated hospitals, and Remote consultation. For AMI patients, different treatment strategies are selected based on the screening results of SARS-CoV-2, the time window of STEMI onset, and the vital signs of the patients. During this special period, the cardiologists, including the interventional physicians, should be fully aware of the indications and contraindications of thrombolysis. In the transport and treatment of AMI patients, the physicians should strictly observe the indications for patient transport with appropriate protective measurements of the medical staff.


Assuntos
Infecções por Coronavirus , Infarto do Miocárdio , Pandemias , Pneumonia Viral , Betacoronavirus , Consenso , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Pandemias/prevenção & controle , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Consulta Remota , Terapia Trombolítica , Transporte de Pacientes
4.
Comput Biol Med ; 119: 103671, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32339116

RESUMO

Epilepsy involves brain abnormalities that may cause sudden seizures or other uncontrollable body activities. Epilepsy may have substantial impacts on the patient's quality of life, and its detection heavily relies on tedious and time-consuming manual curation by experienced clinicians, based on EEG signals. Most existing EEG-based seizure detection algorithms are patient-dependent and train a detection model for each patient. A new patient can only be monitored effectively after several episodes of epileptic seizures. This study investigates the patient-independent detection of seizure events using the open dataset CHB-MIT Scalp EEG. First, a novel feature extraction algorithm called MinMaxHist is proposed to measure the topological patterns of the EEG signals. Following this, MinMaxHist and several other feature extraction algorithms are applied to parameterize the EEG signals. Next, a comprehensive series of feature screening and classification optimization experiments are conducted, and finally, an optimized EEG-based seizure detection model is presented that can achieve overall values for accuracy, sensitivity, specificity, Matthews correlation coefficient, and Kappa of 0.8627, 0.8032, 0.9222, 0.7504 and 0.7254, respectively, with only 30 features. The classification accuracy of the method with MinMaxHist features was 0.0464 higher than that without MinMaxHist features. Compared with existing methods, the proposed algorithm achieved higher accuracy and sensitivity, as shown in the experimental results.

5.
PLoS One ; 15(4): e0232087, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348325

RESUMO

Many proteins exist in natures as oligomers with various quaternary structural attributes rather than as single chains. Predicting these attributes is an essential task in computational biology for the advancement of proteomics. However, the existing methods do not consider the integration of heterogeneous coding and the accuracy of subunit categories with limited data. To this end, we proposed a tool that can predict more than 12 subunit protein oligomers, QUATgo. Meanwhile, three kinds of sequence coding were used, including dipeptide composition, which was used for the first time to predict protein quaternary structural attributes, and protein half-life characteristics, and we modified the coding method of the functional domain composition proposed by predecessors to solve the problem of large feature vectors. QUATgo solves the problem of insufficient data for a single subunit using a two-stage architecture and uses 10-fold cross-validation to test the predictive accuracy of the classifier. QUATgo has 49.0% cross-validation accuracy and 31.1% independent test accuracy. In the case study, the accuracy of QUATgo can reach 61.5% for predicting the quaternary structure of influenza virus hemagglutinin proteins. Finally, QUATgo is freely accessible to the public as a web server via the site http://predictor.nchu.edu.tw/QUATgo.

6.
Cell Commun Signal ; 18(1): 50, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228589

RESUMO

Interleukin (IL)-9 belongs to the IL-2Rγc chain family and is a multifunctional cytokine that can regulate the function of many kinds of cells. It was originally identified as a growth factor of T cells and mast cells. In previous studies, IL-9 was mainly involved in the development of allergic diseases, autoimmune diseases and parasite infections. Recently, IL-9, as a double-edged sword in the development of cancers, has attracted extensive attention. Since T-helper 9 (Th9) cell-derived IL-9 was verified to play a powerful antitumor role in solid tumors, an increasing number of researchers have started to pay attention to the role of IL-9-skewed CD8+ T (Tc9) cells, mast cells and Vδ2 T cell-derived IL-9 in tumor immunity. Here, we review recent studies on IL-9 and several kinds of IL-9-producing cells in tumor immunity to provide useful insight into tumorigenesis and treatment. Video Abstract.

7.
Mikrochim Acta ; 187(4): 221, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166378

RESUMO

A luminescent metal organic framework was prepared by encapsulating Zn-Ag-In-S quantum dots into "French fries"-like MIL-68(In) metal organic frameworks (ZAISQDs@MIL-68(In)). The ZAISQDs@MIL-68(In) had a maximum excitation wavelength at 370 nm and maximum emission wavelength at 620 nm. It was found that the ZAISQDs@MIL-68(In) was efficiently quenched by cytochrome c (Cyt c), which is an important biomarker of early cell apoptosis. The quenching mechanism was ascribed to be an inner filter effect and dynamic quenching of Cyt c towards the ZAISQDs@MIL-68(In), and the enrichment effect of MIL-68(In). Benefiting from the multiple advantages, ZAISQDs@MIL-68(In) was developed as an assay strategy of Cyt c with logarithmic relation between signal quenching and concentration in the range 0.02 to 3.5 µM. The linear equation was (F0-F)/F0 = 0.5043 + 0.2678 × logcCyt c with a detection limit of 8 nM. Cyt c released by drug induced apoptotic cells was determined by ZAISQDs@MIL-68(In), and this strategy has been utilized for the screening of anticancer drug activity. Graphical abstract Schematic representation of the synthesis of ZAISQDs@MIL-68(In) and its application for Cyt c and screening anticancer drug activity.

8.
Cell Immunol ; 352: 104085, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32201004

RESUMO

Asthma is a disease of the respiratory system that is commonly considered a T-helper 2 (Th2) cell-associated inflammatory disease. Group 2 innate lymphoid cells (ILC2s) promote the inflammatory responses in asthma by secreting type 2 cytokines. Interleukin (IL)-9 also serves as a promoting factor in asthma and it is well known that ILC2s have an autocrine effect of IL-9 to sustain their survival and proliferation. However, the specific role of ILC2-derived IL-9 in asthma remains unclear. HMGB1 (High-Mobility Group Box-1) is a nuclear protein, and Previous studies have shown that HMGB1 can regulate the differentiation of T-helper cells and participate in the development of asthma. But whether HMGB1 can regulate the innate lymphocytes in the pathological process of asthma is unknown. In this study we have shown increased presence of HMGB1 protein in the lung of mice with asthma, which was associated with increased secretion of IL-9 by ILC2s. This led to the activation of dendritic cells (DCs) that can accelerate the differentiation of Th2 cells and worsen the severity of asthma. Taken together, our study provides a complementary understanding of the asthma development and highlights a novel inflammatory pathway in the pathogenesis of asthma.

9.
J Chromatogr A ; 1620: 461036, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32201039

RESUMO

Leaves, flowers, fruits and stems (44 sample groups) were collected from mature Camptotheca acuminate during 2017.3-2018.3 and classified by ultra-high performance liquid chromatography coupled with quadrupole-time of flight-mass spectrometry based metabolomics. One hundred metabolites including forty-seven alkaloids, fifteen terpenes, thirty-two polyphenols and six other metabolites were rapidly identified through the in-house database alignment at first glance. Thirty-three alkaloids classified into five groups including camptothecin group (CG1-13), pumiloside group (PG1-5), strictosidinic acid group (SG1-3), vincosamide group (VG1-7), and a new hybrid group, vincosamide-camptothecin group (VC1-5) were mined and further characterized by MS/MS analyses. The identification of two untapped biosynthetic precursors, 2-hydroxypumiloside (PG2) and 16­hydroxy­15, 16-dihydrocamptothecoside (CG3), along with sixteen new alkaloids enables us for a better understanding of camptothecin biogenetic reasoning. The underlying enzymes involved in camptothecin biosynthesis were also proposed according to the guiding metabolic map, thus purposefully mining of enzymes involved in the downstream biosynthetic pathway of camptothecin could be initiated with the help of this map.

10.
Biomed Res Int ; 2020: 1593068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185192

RESUMO

Background: High-altitude headache (HAH) is the most common complication after high-altitude exposure. Hypoxia-inducible factor- (HIF-) related genes have been confirmed to contribute to high-altitude acclimatization. We aim to investigate a possible association between HIF-related genes and HAH in the Chinese Han population. Methods: In total, 580 healthy Chinese Han volunteers were recruited in Chengdu (500 m) and carried to Lhasa (3700 m) by plane in 2 hours. HAH scores and basic physiological parameters were collected within 18-24 hours after the arrival. Thirty-five single nucleotide polymorphisms (SNPs) in HIF-related genes were genotyped, and linkage disequilibrium (LD) was evaluated by Haploview software. The functions of SNPs/haplotypes for HAH were developed by using logistic regression analysis. Results: In comparison with wild types, the rs4953354 "G" allele (P=0.013), rs6756667 "A" allele (P=0.013), rs6756667 "A" allele (EPAS1, and rs6520015 "C" allele in PPARA (P=0.013), rs6756667 "A" allele (PPARA (P=0.013), rs6756667 "A" allele (EPAS1, and rs6520015 "C" allele in PPARA (P=0.013), rs6756667 "A" allele (. Conclusions: EPAS1 and PPARA polymorphisms were associated with HAH in the Chinese Han population. Our findings pointed out potentially predictive gene markers, provided new insights into understanding pathogenesis, and may further provide prophylaxis and treatment strategies for HAH.EPAS1, and rs6520015 "C" allele in PPARA (.

11.
Sci Rep ; 10(1): 5414, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214168

RESUMO

Previous investigations have indicated that environmental and genetic factors collectively contribute to the development of acute mountain sickness (AMS), but whether the EDN1 gene is involved in AMS remains to be elucidated. A total of 356 healthy male soldiers who had not traveled to high altitudes in the previous 12 months were enrolled in our study. All participants were taken by plane from 500 m (Chengdu in Sichuan Province) to a 3700 m highland (Lhasa) within 2 hours. Clinical data were collected within 24 hours, and pulmonary function parameters were completed simultaneously. Genotypes were obtained by using iMLDR genotyping assays. A total of 237 soldiers (66.57%) presented AMS symptoms, including headache, dizziness, gastrointestinal upset and fatigue. Soldiers with AMS showed an increase in heart rate (HR), plasma tryptophan and serotonin, and a decrease in SaO2, FEV1, PEF, FVC, V75, V50, V25 and MMF (all P < 0.01). Notably, allele T in single nucleotide polymorphism (SNP) rs2070699 showed a positive correlation with the occurrence of AMS. A general linear regression analysis showed that rs2060799, Mean Arterial Pressure (MAP), SaO2, FVC, tryptophan and serotonin were independent predictors for the occurrence of AMS. Importantly, the area under the curve (AUC) values for tryptophan (0.998), serotonin (0.912) and FVC (0.86) had diagnostic specificity and sensitivity. Our results demonstrated that AMS is accompanied by changes in lung function parameters, increased plasma tryptophan and serotonin levels, and that the EDN1 polymorphism is a potential risk factor for AMS.

12.
Anal Chem ; 92(8): 6026-6033, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32202417

RESUMO

Cross-linking mass spectrometry (XL-MS) has become a powerful structural tool for defining protein-protein interactions (PPIs) and elucidating architectures of large protein assemblies. To advance XL-MS studies, we have previously developed a series of sulfoxide-containing MS-cleavable cross-linkers to facilitate the detection and identification of cross-linked peptides using multistage mass spectrometry (MSn). While current sulfoxide-based cross-linkers are effective for in vivo and in vitro XL-MS studies at the systems-level, new reagents are still needed to help expand PPI coverage. To this end, we have designed and synthesized six variable-length derivatives of disuccinimidyl sulfoxide (DSSO) to better understand the effects of spacer arm modulation on MS-cleavability, fragmentation characteristics, and MS identification of cross-linked peptides. In addition, the impact on cross-linking reactivity was evaluated. Moreover, alternative MS2-based workflows were explored to determine their feasibility for analyzing new sulfoxide-containing cross-linked products. Based on the results of synthetic peptides and a model protein, we have further demonstrated the robustness and predictability of sulfoxide chemistry in designing MS-cleavable cross-linkers. Importantly, we have identified a unique asymmetric design that exhibits preferential fragmentation of cross-links over peptide backbones, a desired feature for MSn analysis. This work has established a solid foundation for further development of sulfoxide-containing MS-cleavable cross-linkers with new functionalities.

13.
Proc Natl Acad Sci U S A ; 117(8): 4088-4098, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32034103

RESUMO

The COP9 signalosome (CSN) is an evolutionarily conserved eight-subunit (CSN1-8) protein complex that controls protein ubiquitination by deneddylating Cullin-RING E3 ligases (CRLs). The activation and function of CSN hinges on its structural dynamics, which has been challenging to decipher by conventional tools. Here, we have developed a multichemistry cross-linking mass spectrometry approach enabled by three mass spectometry-cleavable cross-linkers to generate highly reliable cross-link data. We applied this approach with integrative structure modeling to determine the interaction and structural dynamics of CSN with the recently discovered ninth subunit, CSN9, in solution. Our results determined the localization of CSN9 binding sites and revealed CSN9-dependent structural changes of CSN. Together with biochemical analysis, we propose a structural model in which CSN9 binding triggers CSN to adopt a configuration that facilitates CSN-CRL interactions, thereby augmenting CSN deneddylase activity. Our integrative structure analysis workflow can be generalized to define in-solution architectures of dynamic protein complexes that remain inaccessible to other approaches.

14.
J Proteome Res ; 19(4): 1788-1799, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32105074

RESUMO

Phosphorylation is crucial in regulating various biological processes. However, comprehensive phosphoproteomic profiling in the termination of liver regeneration (LR) is still missing. Here, we used Tandem Mass Tag (TMT) labeling coupled with phosphopeptide enrichment and two-dimensional (2D) liquid chromatography-mass spectrometry (LC-MS)/MS analysis to establish a global phosphoproteomic map in the liver of mice at day 5 after partial hepatectomy (PH). Altogether, 9731 phosphosites from 3443 proteins were identified and 7802 phosphosites from 2980 proteins were quantified. Motif analysis of the identified phosphosites revealed a diverse array of consensus sequences, suggesting that multiple kinase families including ERK/MAPK, PKA/PKC, CaMK-II, CKII, and CDK may be involved in the termination of LR. Functional clustering analysis of proteins with dysregulated phosphosites showed that they mainly participate in metabolic pathways, DNA replication, and tight junction. More importantly, the deletion of PP2Acα in the liver remarkably changes the overall phosphorylation profile, indicating its critical role in regulating the termination of LR. Finally, several differentially phosphorylated sites were validated by co-immunoprecipitation and Western blot. Taken together, our data unravel the first comprehensive phosphoproteomic map in the termination of LR in mice, which greatly expands our knowledge in the complicated regulation of this process and provides new directions for the treatment of liver cancer using liver resection.

15.
Ther Innov Regul Sci ; 54(1): 211-219, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32008238

RESUMO

BACKGROUND: The US Food and Drug Administration conducts on-site inspections and data audits through Bioresearch Monitoring program for assurance of the quality and integrity of data in the pre- and postapproval processes. It is important to inspect the study sites that are different compared with other sites in clinical studies and identify the problems related to those sites. Usually one cannot inspect all the sites in a clinical study because of limited resources, and statistical tools are needed to help in selecting sites for inspection. METHODS: We propose two technical approaches, namely Fisher combination approach and likelihood ratio test (LRT) approach, for site selection, with each approach integrating the information obtained from a P value matrix. The proposed approaches produce site rankings, and the sites with highest rankings may be selected for inspection. RESULTS: The application of the approaches is demonstrated through a hypothetical data set reflecting the pattern of the real data in a premarket approval submission for a diagnostic device. The proposed methods are shown, through extensive simulations, to control false discovery rate, while maintaining good sensitivity. CONCLUSION: The proposed approaches will be useful for site selection process. However, limitations exist when only using the statistical approaches proposed here. In practice, investigators will select the site for inspection by considering the outputs from the statistical approaches along with other important factors. Future research topic is discussed to facilitate practical application of the approaches.

16.
Brief Bioinform ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020158

RESUMO

Empowered by the advancement of high-throughput bio technologies, recent research on body-fluid proteomes has led to the discoveries of numerous novel disease biomarkers and therapeutic drugs. In the meantime, a tremendous progress in disclosing the body-fluid proteomes was made, resulting in a collection of over 15 000 different proteins detected in major human body fluids. However, common challenges remain with current proteomics technologies about how to effectively handle the large variety of protein modifications in those fluids. To this end, computational effort utilizing statistical and machine-learning approaches has shown early successes in identifying biomarker proteins in specific human diseases. In this article, we first summarized the experimental progresses using a combination of conventional and high-throughput technologies, along with the major discoveries, and focused on current research status of 16 types of body-fluid proteins. Next, the emerging computational work on protein prediction based on support vector machine, ranking algorithm, and protein-protein interaction network were also surveyed, followed by algorithm and application discussion. At last, we discuss additional critical concerns about these topics and close the review by providing future perspectives especially toward the realization of clinical disease biomarker discovery.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32073210

RESUMO

AIM: Fetal bowel dilatation (FBD) in the late trimester of pregnancy can be related with varies of prognosis. Our aims were to obtain antenatal factors that might have relevance for the distinct prognosis with FBD. METHODS: Seven features of 68 pregnancies presented with FBD were assessed. The best cut-off value to predict intestinal outcomes was selected using receiver-operating characteristics curves, and the effective variables were included into a logistic regression model. RESULTS: The best cut-off valves to predict intestinal pathologies were 14.5 mm of fetus dilated loop and 37.7 weeks of gestational age at delivery, respectively. The congenital gastrointestinal tract anomalies included 24 cases (92.3%) of intestine atresia, 1 case (3.85%) of small intestine volvulus and 1 case (3.85%) of midgut malrotation. CONCLUSION: Fetal dilated loops and gestational age at delivery are both an independent risk factor for predicting intestinal pathologies of newborns, which should arouse high attention.

18.
J Am Chem Soc ; 142(10): 4732-4738, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058715

RESUMO

The continuous variation of the lattice metric in metal-organic frameworks (MOFs) allows precise control over their chemical and physical properties. This has been realized herein by a series of mixed-linker and Zr6-cluster-based MOFs, namely, continuously variable MOFs (CVMOFs). Similar to the substitutional solid solutions, organic linkers with different lengths and various ratios were homogeneously incorporated into a framework rather than being allowed to form separate phases or domains, which was manifested by single-crystal X-ray diffraction, powder X-ray diffraction, fluorescence quenching experiments, and molecular simulations. The unit cell dimension, surface area, and pore size of CVMOFs were precisely controlled by adopting different linker sets and linker ratios. We demonstrate that CVMOFs allow the continuous and fine tailoring of cell-edge lengths from 17.83 to 32.63 Å, Brunauer-Emmett-Teller (BET) surface areas from 585 to 3791 m2g-1, and pore sizes up to 15.9 Å. Furthermore, this synthetic strategy can be applied to other MOF systems with various metal nodes thus allowing for a variety of CVMOFs with unprecedented tunability.

19.
Int J Cardiovasc Imaging ; 36(5): 799-810, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31953650

RESUMO

High-altitude (HA) exposure has been widely considered as a cardiac stress, and associated with altered cardiac function. However, the characteristics of cardiac responses to HA exposure are unclear. In total, 240 healthy men were enrolled and ascended to 4100 m by bus within 7 days. Standard echocardiography and color tissue Doppler imaging were performed at sea level and at 4100 m. In all subjects, HA exposure increased HR [65 (59, 71) vs. 72 (63, 80) beats/min, p < 0.001] but decreased the stroke volume index (SVi) [35.5 (30.5, 42.3) vs. 32.9 (27.4, 39.5) ml/m2, p < 0.001], leading to an unchanged cardiac index (CI). Moreover, baseline HR was negatively correlated with HA exposure-induced changes in HR (r = - 0.410, p < 0.001) and CI (r = - 0.314, p < 0.001). Following HA exposure, subjects with lowest tertile of baseline HR showed an increased HR [56 (53, 58) vs. 65 (58, 73) beats/min, p < 0.001], left ventricular ejection fraction (LVEF) [61.7 (56.5, 68.0) vs. 66.1 (60.7, 71.5) %, p = 0.004] and mitral S' velocity [5.8 ± 1.4 vs. 6.5 ± 1.9 cm/s, p = 0.040]. However, subjects with highest tertile of baseline HR showed an unchanged HR, LVEF and mitral S' velocity, but a decreased E' velocity [9.2 ± 2.0 vs. 8.4 ± 1.8 cm/s, p = 0.003]. Our findings indicate that baseline HR at sea level could determine cardiac responses to HA exposure; these responses were characterized by enhanced LV function in subjects with a low baseline HR and by reduced LV myocardial velocity in early diastole in subjects with a high baseline HR.

20.
J Proteome Res ; 19(3): 1119-1130, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31950832

RESUMO

The COP9 signalosome (CSN) is an evolutionarily conserved multisubunit protein complex, which controls protein degradation through deneddylation and inactivation of cullin-RING ubiquitin E3 ligases (CRLs). Recently, the CSN complex has been linked to the NF-κB signaling pathway due to its association with the IKK complex. However, how the CSN complex is regulated in this signaling pathway remains unclear. Here, we have carried out biochemical experiments and confirmed the interaction between the CSN and IKK complexes. In addition, we have determined that overexpression of IKKα or IKKß leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro. Interestingly, TNF-α treatment not only enhances the interaction between CSN and IKK but also induces an IKK-dependent phosphorylation of CSN5 at serine 201, linking CSN to TNF-α signaling through IKK. Moreover, TNF-α treatment affects the CSN interaction network globally, especially the associations of CSN with the proteasome complex, eukaryotic translation initiation factor complex, and CRL components. Collectively, our results provide new insights into IKK-mediated regulation of CSN associated with the NF-κB signaling pathway.

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