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1.
EMBO J ; 40(18): e105658, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34260076

RESUMO

The Ebola virus VP30 protein interacts with the viral nucleoprotein and with host protein RBBP6 via PPxPxY motifs that adopt non-canonical orientations, as compared to other proline-rich motifs. An affinity tag-purification mass spectrometry approach identified additional PPxPxY-containing host proteins hnRNP L, hnRNPUL1, and PEG10, as VP30 interactors. hnRNP L and PEG10, like RBBP6, inhibit viral RNA synthesis and EBOV infection, whereas hnRNPUL1 enhances. RBBP6 and hnRNP L modulate VP30 phosphorylation, increase viral transcription, and exert additive effects on viral RNA synthesis. PEG10 has more modest inhibitory effects on EBOV replication. hnRNPUL1 positively affects viral RNA synthesis but in a VP30-independent manner. Binding studies demonstrate variable capacity of the PPxPxY motifs from these proteins to bind VP30, define PxPPPPxY as an optimal binding motif, and identify the fifth proline and the tyrosine as most critical for interaction. Competition binding and hydrogen-deuterium exchange mass spectrometry studies demonstrate that each protein binds a similar interface on VP30. VP30 therefore presents a novel proline recognition domain that is targeted by multiple host proteins to modulate viral transcription.


Assuntos
Ebolavirus/fisiologia , Doença pelo Vírus Ebola/metabolismo , Doença pelo Vírus Ebola/virologia , Prolina/metabolismo , Tirosina/metabolismo , Proteínas de Transporte , Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Ligação Proteica , Replicação Viral
2.
Nat Mater ; 22(12): 1499-1506, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37770677

RESUMO

Recently, the increasing demand for data-centric applications is driving the elimination of image sensing, memory and computing unit interface, thus promising for latency- and energy-strict applications. Although dedicated electronic hardware has inspired the development of in-memory computing and in-sensor computing, folding the entire signal chain into one device remains challenging. Here an in-memory sensing and computing architecture is demonstrated using ferroelectric-defined reconfigurable two-dimensional photodiode arrays. High-level cognitive computing is realized based on the multiplications of light power and photoresponsivity through the photocurrent generation process and Kirchhoff's law. The weight is stored and programmed locally by the ferroelectric domains, enabling 51 (>5 bit) distinguishable weight states with linear, symmetric and reversible manipulation characteristics. Image recognition can be performed without any external memory and computing units. The three-in-one paradigm, integrating high-level computing, weight memorization and high-performance sensing, paves the way for a computing architecture with low energy consumption, low latency and reduced hardware overhead.

3.
Phys Chem Chem Phys ; 26(14): 10974-10981, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38526392

RESUMO

Bulk Dirac semimetals (BDSs) possess Fermi energy dependent optical parameters, providing unprecedented opportunities for the study of the controllable Goos-Hänchen (GH) shift. However, the enhancement of GH shifts often comes at the cost of the reflectance in the previous BDS-based structures, which hinders their practical application. In this work, we theoretically present the investigation of the GH shift in a multilayered structure composed of one BDS film and a symmetric one-dimensional photonic crystal (1DPC) with a defect layer. We demonstrate that this well-designed structure supports a large GH shift at the specific working wavelength, whose magnitude can be enhanced up to 3883 times the incident wavelength. In particular, such an enhanced GH shift achieved in this structure is associated with high reflectance (0.94) and these remarkable features can be attributed to the sharp change in the reflective phase and the destructive interference that occurs between the simultaneously excited optical Tamm state (OTS) at the BDS/1DPC interface and the defect state at the 1D defected PC. In addition, we also explore the manipulation of the GH shift by adjusting the Fermi energy of the BDS as well as the geometrical parameter of the multilayered structure. Our results provide a new approach for realizing an enhanced and controllable GH shift in a BDS-based multilayered structure, which endows it with promising prospects for application in optical sensors, optical detectors and beam controllers.

4.
J Environ Sci (China) ; 142: 43-56, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38527895

RESUMO

Alkali metal potassium was beneficial to the electronic regulation and structural stability of transition metal oxides. Herein, K ions were introduced into manganese oxides by different methods to improve the degradation efficiency of toluene. The results of activity experiments indicated that KMnO4-HT (HT: Hydrothermal method) exhibited outstanding low-temperature catalytic activity, and 90% conversion of toluene can be achieved at 243°C, which was 41°C and 43°C lower than that of KNO3-HT and Mn-HT, respectively. The largest specific surface area was observed on KMnO4-HT, facilitating the adsorption of toluene. The formation of cryptomelane structure over KMnO4-HT could contribute to higher content of Mn3+ and lattice oxygen (Olatt), excellent low-temperature reducibility, and high oxygen mobility, which could increase the catalytic performance. Furthermore, two distinct degradation pathways were inferred. Pathway Ⅰ (KMnO4-HT): toluene → benzyl → benzoic acid → carbonate → CO2 and H2O; Pathway ⅠⅠ (Mn-HT): toluene → benzyl alcohol → benzoic acid → phenol → maleic anhydride → CO2 and H2O. Fewer intermediates were detected on KMnO4-HT, indicating its stronger oxidation capacity of toluene, which was originated from the doping of K+ and the interaction between KOMn. More intermediates were observed on Mn-HT, which can be attributed to the weaker oxidation ability of pure Mn. The results indicated that the doping of K+ can improve the catalytic oxidation capacity of toluene, resulting in promoted degradation of intermediates during the oxidation of toluene.


Assuntos
Compostos de Manganês , Manganês , Tolueno , Manganês/química , Oxigênio/química , Dióxido de Carbono , Óxidos/química , Oxirredução , Catálise , Ácido Benzoico
5.
J Physiol ; 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37642341

RESUMO

Chronic cough (CC) is a common but poorly understood disease that has a negative impact on quality of life. For years, clinicians have been trying to find the underlying diagnosis and using existing disease models to describe the patients' illness. This presents a confusing picture of CC. Most patients with CC present with hypersensitivity of the cough reflex, which is characterised by laryngeal paraesthesia and an increased response to the tussive stimuli or an innocuous stimulus that would not trigger coughing in healthy people. Recently, it has been proposed that CC is a unique disease characterised by vagal hypersensitivity that projects to the central nervous system altering responsiveness. The evidence supports the hypothesis that CC is primarily a neurological disorder, consisting of different phenotypes.

6.
BMC Plant Biol ; 23(1): 77, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737681

RESUMO

BACKGROUND: Jatropha curcas is a promising alternative bio-energy resource. However, underrun limited its broad application in the industry. Luckily, TAW1 is a high-productivity promoting gene that increases the lateral branches by prolonging the identification of inflorescence meristems to generate more spikes and flowers. RESULTS: In the current study, we introduced the Jatropha JcTAW1 gene into tobacco to depict its functional profile. Ectopically expressed JcTAW1 increased the lateral branches and ultimate yield of the transgenic tobacco plants. Moreover, the JcTAW1 lines had significantly higher plant height, longer roots, and better drought resistance than those of wild-type (W.T.). We performed RNA sequencing and weighted gene co-expression network analysis to determine which biological processes were affected by JcTAW1. The results showed that biological processes such as carbon metabolism, cell wall biosynthesis, and ionization transport were extensively promoted by the ectopic expression of JcTAW1. Seven hub genes were identified. Therein, two up-regulated genes affect glucose metabolism and cell wall biosynthesis, five down-regulated genes are involved in DNA repair and negative regulation of TOR (target-of-rapamycin) signaling which was identified as a central regulator to promote cell proliferation and growth. CONCLUSIONS: Our study verified a new promising candidate for Jatropha productive breeding and discovered several new features of JcTAW1. Except for boosting flowering, JcTAW1 was found to promote stem and root growth. Additionally, transcriptome analysis indicated that JcTAW1 might promote glucose metabolism while suppressing the DNA repair system.


Assuntos
Fenômenos Biológicos , Jatropha , Nicotiana/genética , Resistência à Seca , Expressão Ectópica do Gene , Melhoramento Vegetal , Plantas Geneticamente Modificadas , Glucose/metabolismo , Regulação da Expressão Gênica de Plantas
7.
Int J Clin Pract ; 2023: 7992062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36941872

RESUMO

Background: The clinical management of nonacid gastroesophageal reflux-induced chronic cough (GERC) is challenging, and patient response to standard antireflux therapy (omeprazole 20 mg twice daily plus mosapride 10 mg thrice daily) is suboptimal. This study aimed to identify predictors of standard antireflux therapy efficacy and provide evidence for standardized management algorithms of nonacid GERC. Methods: A total of 115 nonacid GERC patients who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) were enrolled between March 2017 and March 2021. Retrospective analysis of general information and MII-pH indications were used to establish a regression analysis model for multiple factors affecting standard antireflux therapy efficacy. Results: 90 patients met the inclusion criteria, and the overall response rate to standard antireflux therapy was 55.5% (50/90). The mean nocturnal baseline impedance (MNBI) (1817.75 ± 259.26 vs. 2369.93 ± 326.35, P = 0.030) and proximal MNBI (1833.39 ± 92.16 vs. 2742.57 ± 204.64, P ≤ 0.001) of responders were lower than those of nonresponders. Weakly acid reflux (56.00 (31.70, 86.00) vs. 14.00 (14.00, 44.20), P = 0.022), nonacid reflux (61.35 (15.90.86.50) vs. 21.60 (0.00, 52.50), P = 0.008), and proximal extent (19.00 (5.04, 24.00) vs. 5.50 (2.56, 11.13), P = 0.011) were markedly higher in responders than nonresponders. Proximal MNBI (OR = 0.997, P = 0.042, and optimal cutoff = 2140 Ω) and weakly acid reflux (OR = 1.051, P = 0.029, and optimal cutoff = 45) were independent predictors of standard antireflux therapy efficacy. The combination predictive value did not show better results than either individual predictor. Conclusions: Proximal MNBI < 2140 Ω may be used to screen patients with nonacid GERC suitable for standard antireflux therapy and in standardized management algorithms for nonacid GERC. In the absence of MNBI, weakly acid reflux > 45 can be used as an auxiliary indicator.


Assuntos
Monitoramento do pH Esofágico , Refluxo Gastroesofágico , Humanos , Estudos Retrospectivos , Tosse/diagnóstico , Tosse/etiologia , Impedância Elétrica , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Doença Crônica
8.
J Environ Manage ; 348: 119465, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37924697

RESUMO

Grassland degradation poses a serious threat to biodiversity, ecosystem services, and human well-being. In this study, we investigated grassland degradation in Zhaosu County, China, between 2001 and 2020, and analyzed the impacts of climate change and human activities using the Miami model. The actual net primary productivity (ANPP) obtained with CASA (Carnegie-Ames-Stanford Approach) modeling, showed a decreasing trend, reflecting the significant degradation that the grasslands in Zhaosu County have experienced in the past 20 years. Grassland degradation was found to be highest in 2018, while the degraded area continuously decreased in the last 3 years (2018-2020). Climatic factors for found to be the dominant factor affecting grassland degradation, particularly the decrease in precipitation. On the other hand, human activities were found to be the main factor affecting improvement of grasslands, especially in recent years. This finding profoundly elucidates the underlying causes of grassland degradation and improvement and helps implement ecological conservation and restoration measures. From a practical perspective, the research results provide an important reference for the formulation of policies and management strategies for sustainable land use.


Assuntos
Ecossistema , Pradaria , Humanos , Mudança Climática , China , Atividades Humanas
9.
BMC Plant Biol ; 22(1): 570, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36471240

RESUMO

BACKGROUND: Leaf color mutants are ideal materials to study pigment metabolism and photosynthesis. Leaf color variations are mainly affected by chlorophylls (Chls) and carotenoid contents and chloroplast development in higher plants. However, the regulation of chlorophyll metabolism remains poorly understood in many plant species. The chloroplast signal-recognition particle system is responsible for the insertion of the light-harvesting chlorophyll a/b proteins (LHCPs) to thylakoid membranes, which controls the chloroplast development as well as the regulation of Chls biosynthesis post-translationally in higher plants. RESULTS: In this study, the yellow leaf cucumber mutant, named yl, was found in an EMS-induced mutant library, which exhibited a significantly reduced chlorophyll content, abnormal chloroplast ultrastructure and decreased photosynthetic capacity. Genetic analysis demonstrated that the phenotype of yl was controlled by a recessive nuclear gene. Using BSA-seq technology combined with the map-based cloning method, we narrowed the locus to a 100 kb interval in chromosome 3. Linkage analysis and allelism test validated the candidate SNP residing in CsaV3_3G009150 encoding one homolog of chloroplast signal-recognition particle (cpSRP) receptor in Arabidopsis, cpFtsY, could be responsible for the yellow leaf phenotype of yl. The relative expression of CscpFtsY was significantly down-regulated in different organs except for the stem, of yl compared with that in the wild type (WT). Subcellular localization result showed that CscpFtsY located in the chloroplasts of mesophyll cells. CONCLUSIONS: The yl mutant displayed Chls-deficient, impaired chloroplast ultrastructure with intermittent grana stacks and significantly decreased photosynthetic capacity. The isolation of CscpFtsY in cucumber could accelerate the progress on chloroplast development by cpSRP-dependant LHCP delivery system and regulation of Chls biosynthesis in a post-translational way.


Assuntos
Arabidopsis , Cucumis sativus , Cucumis sativus/genética , Cucumis sativus/metabolismo , Clorofila A/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/metabolismo , Cloroplastos/metabolismo , Fenótipo , Clorofila/metabolismo , Arabidopsis/genética , Complexos de Proteínas Captadores de Luz/genética , Partícula de Reconhecimento de Sinal/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação
10.
Theor Appl Genet ; 135(8): 2711-2723, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35788747

RESUMO

KEY MESSAGE: A novel compact plant architecture mutant, cpa-2, was identified from EMS-induced mutagenesis. Bulked segregant analysis sequencing and map-based cloning revealed CsDWF1 encoding C-24 reductase enzyme as the candidate gene. The compact architecture is a vital and valuable agronomic trait that helps to reduce the labor of plant management, and improve the fruit yield by increasing planting density in cucumbers. However, the molecular basis underlying the regulation of plant architecture in cucumber is complex and largely unknown. In this study, a novel recessive compact allele, designated as cpa-2 (compact plant architecture-2) was fine mapped in a 109 kb region on chromosome 7 by the strategy of bulked segregant analysis sequencing combined with map-based cloning. Gene annotation of the corresponding region revealed that the CsaV3_7G030530 (CsDWF1) gene encoding C-24 reductase, which acts as the key enzyme in brassinosteroids biosynthesis, functions as the candidate gene for cpa-2. Sequence analysis showed that a single-nucleotide mutation (G to A) in the second exon of CsaV3_7G030530 caused an amino acid substitution from E502 to K502. Compared with wild-type CCMC, CsDWF1 had lower expression levels in the stem, leaf and ovary of cpa-2. In addition, the compact phenotype in cpa-2 could be partially restored by exogenous BR application. Transcriptome analysis revealed that many genes related to plant growth hormones were differentially expressed in cpa-2 plants. This is the first report about the characterization and cloning of the CsDWF1 gene. This work revealed the importance of CsDWF1 in plant development regulation and extended our understanding of the interaction between BRs and other hormones for plant architecture development.


Assuntos
Cucumis sativus , Brassinosteroides , Mapeamento Cromossômico , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Hormônios , Mutação , Oxirredutases/genética , Fenótipo , Proteínas de Plantas/genética , Esteroides Heterocíclicos
11.
Purinergic Signal ; 18(3): 289-305, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35727480

RESUMO

Chronic cough is the most common complaint in respiratory clinics. Most of them have identifiable causes and some may respond to common disease-modifying therapies. However, there are many patients whose cough lacks effective aetiologically targeted treatments or remains unexplained after thorough assessments, which have been described as refractory chronic cough. Current treatments for refractory chronic cough are limited and often accompanied by intolerable side effects such as sedation. In recent years, various in-depth researches into the pathogenesis of chronic cough have led to an explosion in the development of drugs for the treatment of refractory chronic cough. There has been considerable progress in the underlying mechanisms of chronic cough targeting ATP, and ongoing or completed clinical studies have confirmed the promising antitussive efficacy of P2X3 antagonists for refractory cough. Herein, we review the foundation on which ATP target was developed as potential antitussive medications and provide an update on current clinical progresses.


Assuntos
Antitussígenos , Doença Enxerto-Hospedeiro , Trifosfato de Adenosina , Antitussígenos/efeitos adversos , Doença Crônica , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Humanos , Resultado do Tratamento
12.
Chem Rev ; 120(10): 4355-4454, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32319757

RESUMO

Proteins adopt different higher-order structures (HOS) to enable their unique biological functions. Understanding the complexities of protein higher-order structures and dynamics requires integrated approaches, where mass spectrometry (MS) is now positioned to play a key role. One of those approaches is protein footprinting. Although the initial demonstration of footprinting was for the HOS determination of protein/nucleic acid binding, the concept was later adapted to MS-based protein HOS analysis, through which different covalent labeling approaches "mark" the solvent accessible surface area (SASA) of proteins to reflect protein HOS. Hydrogen-deuterium exchange (HDX), where deuterium in D2O replaces hydrogen of the backbone amides, is the most common example of footprinting. Its advantage is that the footprint reflects SASA and hydrogen bonding, whereas one drawback is the labeling is reversible. Another example of footprinting is slow irreversible labeling of functional groups on amino acid side chains by targeted reagents with high specificity, probing structural changes at selected sites. A third footprinting approach is by reactions with fast, irreversible labeling species that are highly reactive and footprint broadly several amino acid residue side chains on the time scale of submilliseconds. All of these covalent labeling approaches combine to constitute a problem-solving toolbox that enables mass spectrometry as a valuable tool for HOS elucidation. As there has been a growing need for MS-based protein footprinting in both academia and industry owing to its high throughput capability, prompt availability, and high spatial resolution, we present a summary of the history, descriptions, principles, mechanisms, and applications of these covalent labeling approaches. Moreover, their applications are highlighted according to the biological questions they can answer. This review is intended as a tutorial for MS-based protein HOS elucidation and as a reference for investigators seeking a MS-based tool to address structural questions in protein science.


Assuntos
Proteínas/química , Medição da Troca de Deutério , Espectrometria de Massas , Conformação Proteica
13.
J Acoust Soc Am ; 152(5): 2711, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36456303

RESUMO

This paper presents a far-field enhanced-resolution underwater ultrasonic imaging on the basis of a single-slit structured planar focusing lens. The iterative angular spectrum approach was employed to optimize the planar focusing lens from a designated focal pattern, characterized by focal length and full width at half maxima. Numerical simulations and experimental investigations were conducted on different target objects. Compared to the conventional method, both results showed that the performance of far-field ultrasonic imaging was comprehensively enhanced with the proposed planar focusing lens, in terms of resolving capability, working distance, operational bandwidth, and robustness. The single-slit structured planar focusing lens is cost effective and easy to fabricate, which would greatly benefit ultrasonic imaging and drive new applications of ultrasound in various scenarios.

14.
Theor Appl Genet ; 134(7): 2023-2034, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33683399

RESUMO

KEY MESSAGE: By the strategy of bulked segregant analysis sequencing combined with genetic mapping, CsDWF5, which encodes 7 dehydrocholesterol reductase that involved in brassinosteroids biosynthesis, was identified as the candidate gene for cpa. Dwarf architecture is one of the most important breeding goals in crops. The biosynthesis and signal transduction of brassinosteroids (BRs) have a great impact on plant growth and development including plant architecture. Here, we identified a compact plant architecture (cpa) mutant from an EMS-induced cucumber population. cpa displayed the extremely dwarf phenotype with shortened internode and petiole, darkened and wrinkled leaf. Genetic analysis revealed that cpa was caused by a single recessive gene. By the strategy of bulked segregant analysis sequencing combined with genetic mapping, CsDWF5, encoding a 7-dehydrocholesterol reductase that involved in sterol biosynthesis, was identified as the candidate gene for cpa. One single nucleotide mutation (G→A) in splicing site causing 3-bp insertion (TAG) was found in the first base of the sixth intron of CsDWF5 in cpa, which furtherly resulted in the frameshift mutation and got a premature stop codon. The expression of CsDWF5 gene was significantly down regulated in different tissues of the cpa mutant compared with that in wild type. The phenotype of cpa could be partially recovered by exogenous BR treatment. Transcriptome analysis identified 1096 genes that exhibited differential expression between the cpa mutant and wild type. KEGG enrichment analysis indicated that differentially expressed genes were significantly enriched in BR biosynthesis and plant-pathogen interaction pathways. These results provide perspectives on the molecular mechanisms underlying the dwarfing phenotype in cucumber.


Assuntos
Brassinosteroides/biossíntese , Cucumis sativus/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Sequência de Aminoácidos , Mapeamento Cromossômico , Códon sem Sentido , Cucumis sativus/enzimologia , Mutação da Fase de Leitura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Genes Recessivos , Fenótipo
15.
J Environ Manage ; 290: 112586, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33865158

RESUMO

High salinity wastewater generally resulted in microorganism death and low treatment efficiency of nutrient in conventional activity sludge system. Marine sediments, containing a huge amount of natural salt-tolerant microorganisms, provide a feasible option for the rapid construction of halophilic biological treatment system. However, the dynamic of native microorganisms and the fate of soluble microbial products (SMP) in halophilic biofilm system developed from marine sediments needs to be further studied. In this study, a partial nitrification system was successfully established by inoculation of marine sediments in sequential batch biofilm reactor. Satisfactory chemical oxygen demand (COD) and NH4+-N removal efficiency (95% and 99%) and nitrite accumulation rate (NAR) (>90%) was achieved for treatment of synthetic seawater blackwater. High cell surface hydrophobicity (CSH) and proteins to polysaccharide ratio of extracellular polymeric substance (EPS) were beneficial to the initial biofilm formation. High-throughput sequencing results revealed Nitrosomonas halophila was the sole ammonia oxidizing bacteria (AOB). Thauera and Paracoccus were the main denitrifying bacteria in three biofilm samples. Excitation emission matrix (EEM) spectroscopy coupled with parallel factor analysis (PARAFAC) clarified that proteins were significantly degraded than the other two components (humic-like and fulvic acid-like substance). This study will provide a feasible approach for developing halophilic biological treatment system and present an in-depth insight of the dynamic characteristics of SMP in partial nitrification biofilm system.


Assuntos
Microbiota , Nitrificação , Biofilmes , Reatores Biológicos , Matriz Extracelular de Substâncias Poliméricas , Sedimentos Geológicos , Nitrogênio , Nitrosomonas , Salinidade , Esgotos , Águas Residuárias
16.
Chron Respir Dis ; 18: 14799731211006682, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33779345

RESUMO

OBJECTIVES: To elucidate the accuracy and advantages of Multichannel intraluminal impedance-pH monitoring (MII-pH) in diagnosing gastroesophageal reflux-induced chronic cough (GERC). METHODS: The patients with suspected GERC were recruited and underwent MII-pH, GERC was confirmed by subsequent anti-reflux treatment despite the findings of MII-pH. Its diagnostic accuracy in identifying GERC were evaluated by receiver operating characteristic (ROC) analysis and compared with that of 24-h esophageal pH monitoring. RESULTS: Among 158 patients completing both MII-pH and anti-reflux therapy, GERC was diagnosed in 136 patients, including acid GERC in 96 patients (70.6%), non-acid GERC in 30 patients (22.0%), neither one of both GERC in 10 patients (7.4%). For the identification of GERC, MII-pH presented with the sensitivity of 92.6%, specificity of 63.6%, positive predictive value of 94.0%, negative predictive value of 58.3% and area under ROC curve of 0.863, which was totally superior to 24-h esophageal pH monitoring. As the essential criteria of MII-pH, esophageal acid exposure time and symptom associated probability had a limited diagnostic value when used alone, but improved greatly the diagnostic yield when used in combination, even with a suboptimal efficacy. CONCLUSION: MII-pH is a more sensitive test for identifying GERC, but with a suboptimal diagnostic efficacy.


Assuntos
Tosse , Refluxo Gastroesofágico , Tosse/diagnóstico , Tosse/etiologia , Impedância Elétrica , Monitoramento do pH Esofágico , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Humanos , Concentração de Íons de Hidrogênio
17.
Anal Chem ; 92(13): 9086-9094, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32441507

RESUMO

Programmed cell death-1 (PD-1), an antigen co-receptor on cell surfaces, is one of the conspicuous immune checkpoints. Nivolumab, a monoclonal antibody therapeutic approved by the FDA, binds to PD-1 and efficiently blocks its pathways. In this study, an integrated approach was developed to map the epitope/paratope of PD-1/nivolumab. The approach includes hydrogen-deuterium exchange mass spectrometry (HDX-MS) followed by electron-transfer dissociation (ETD), chemical cross-linking, and molecular docking. HDX-ETD offers some binding-site characterization with amino acid resolution. Chemical cross-linking provides complementary information on one additional epitope (i.e., the BC-loop) and a potential paratope at the N-terminus of the heavy chain. Furthermore, cross-linking identifies another loop region (i.e., the C'D-loop) that undergoes a remote conformational change. The distance restraints derived from the cross-links enable building high-confidence models of PD-1/nivolumab, evaluated with respect to a resolved crystal structure. This integrated strategy is an opportunity to characterize comprehensively other antigen-antibody interactions, to enable the understanding of binding mechanisms, and to design future antibody therapeutics.


Assuntos
Medição da Troca de Deutério , Mapeamento de Epitopos/métodos , Epitopos/análise , Nivolumabe/imunologia , Receptor de Morte Celular Programada 1/imunologia , Sequência de Aminoácidos , Complexo Antígeno-Anticorpo/química , Sítios de Ligação , Cromatografia Líquida de Alta Pressão , Epitopos/química , Epitopos/imunologia , Humanos , Simulação de Acoplamento Molecular , Nivolumabe/metabolismo , Receptor de Morte Celular Programada 1/química , Receptor de Morte Celular Programada 1/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , Espectrometria de Massas em Tandem
19.
Theor Appl Genet ; 133(2): 371-382, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31734868

RESUMO

KEY MESSAGE: Via bulked segregant analysis sequencing combined with linkage mapping, the ist gene responsible for the irregularly striped rind mutation was delimited to a 144-kb region in cucumber. Sequencing and expression analysis identified Csa1G005490 as the candidate gene. The rind appearance of cucumber is one of the most important commercial quality traits. Usually, an immature cucumber fruit has a uniform rind that varies from green to yellow to white among different cultivated varieties. In the present paper, we isolated a novel fruit appearance cucumber mutant, ist, that has an irregularly striped rind pattern. The mutant displayed green irregular stripes on a yellow-green background at the immature fruit stage. Genetic analysis revealed that a single recessive gene, ist, is responsible for this mutation. A BSA (bulked segregant analysis) sequencing approach combined with genetic mapping delimited the ist locus to an interval with a length of 144 kb, and 21 predicted genes were annotated in the region. Based on mutation site screening and expression analysis, two single-nucleotide polymorphisms within the candidate gene, Csa1G005490, were identified as constituting the mutation. Csa1G005490 encodes a polygalacturonase-1 noncatalytic subunit beta protein (PG1ß) known to be involved in fruit softening. The expression of Csa1G005490 was significantly lower in the ist mutant than in the wild type. Transcriptome analysis identified 1796 differentially expressed genes (DEGs) between the ist mutant and wild type. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were enriched mostly in photosynthesis and chlorophyll metabolism pathways. Decreased expression patterns of several chlorophyll synthesis genes in the mutant suggest that ist plays a key role in chlorophyll biosynthesis. These results will provide new insight into the molecular mechanism underlying rind appearance polymorphisms in cucumber.


Assuntos
Cucumis sativus/genética , Frutas/genética , Regulação da Expressão Gênica de Plantas/genética , Poligalacturonase/genética , Clorofila/genética , Clorofila/metabolismo , Cloroplastos/metabolismo , Cloroplastos/ultraestrutura , Mapeamento Cromossômico , Cucumis sativus/metabolismo , Frutas/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Genes de Plantas , Genes Recessivos , Microscopia Eletrônica de Transmissão , Mutação , Fenótipo , Fotossíntese/genética , Proteínas de Plantas/genética , Poligalacturonase/metabolismo , Polimorfismo de Nucleotídeo Único , RNA-Seq , Transdução de Sinais/genética
20.
Soc Psychiatry Psychiatr Epidemiol ; 55(2): 251-257, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31115597

RESUMO

PURPOSE: There is evidence that social isolation or loneliness may be associated with mental health. However, it is unclear to what extent these two factors independently affect mental health and if these effects are gender dependent. This study examined the simultaneous associations of social isolation and loneliness with depressive symptoms in a longitudinal study of male and female college students. METHODS: Data were analyzed from 741 college students (28.3% males, 71.7% females; mean age = 18.47, SD = 0.87) at Tianjin Medical University. Multiple linear regression models were conducted to test the independent, relative, and synergistic effects of baseline isolation and loneliness on depressive symptoms at follow-up for female and male college students separately. All analyses were adjusted for baseline depressive symptoms and personality traits. RESULTS: Gender differences were found for the prospective associations of social isolation and loneliness with depressive symptoms. For females, either baseline isolation (ß = 0.22, p < 0.001) or loneliness (ß = 0.23, p < 0.001) can significantly predict the increased depressive symptoms. For males, baseline isolation (ß = 0.25, p < 0.01) rather than loneliness (ß = 0.14, p > 0.05) can significantly predict depressive symptoms. CONCLUSIONS: This longitudinal study found a gender-dependent impact of isolation and loneliness on depressive symptoms. These results indicated that female and male college students may require different interventions to help them adjust to college life.


Assuntos
Depressão/psicologia , Solidão/psicologia , Fatores Sexuais , Isolamento Social/psicologia , Estudantes/psicologia , Adolescente , Adulto , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Estudos Prospectivos , Universidades , Adulto Jovem
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