Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
Int J Chron Obstruct Pulmon Dis ; 16: 2697-2706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34611398

RESUMO

Background: Pneumoconiosis has high prevalence of chronic obstructive pulmonary disease (COPD), respiratory morbidity, and mortality. Objective: The aim of the present study was to examine patient characteristics and adherence to inhaled therapy among pneumoconiosis with COPD in a real-world clinical setting. Methods: A cohort of pneumoconiosis patients with COPD prescript with at least one type of long-acting inhaled drug was followed for adherence for 2 years. Demographic and COPD-related characteristics were collected in baseline. Results: In baseline, after adjusting for age, dust exposure duration positively correlated with number of acute exacerbation (AE) frequency in the last year. There were close associations among COPD Assessment Tool (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC) grade, number of AE, and pre-FEV1 value. Of 296 participants originally recruited, 213 participants finished the 2-year follow-up for adherence. 122 (57.28%) were non-adherent to inhaled therapy. The most common reason for non-adherence was "relief of symptoms after short-term controller medication use" (53.28%). Patients who were non-adherent reported higher body mass index (BMI), less AE events in the last year, higher pre-FEV1 value, higher post-FEV1 value and low CAT, mMRC scores compared to adherent in baseline. High pre-FEV1 value (OR = 1.04, CI = 1.018-1.064) and low mMRC scores (OR = 0.406, CI = 0.214-0.771) were risk factors found associated with non-adherence. Conclusion: A majority of pneumoconiosis patients complicated with COPD have suboptimal inhaled therapy adherence. Evidence-based, adherence-enhancing interventions should be targeted on less severe subjects.


Assuntos
Pneumoconiose , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Humanos , Pneumoconiose/diagnóstico , Pneumoconiose/tratamento farmacológico , Pneumoconiose/epidemiologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória
2.
Proc Natl Acad Sci U S A ; 118(36)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34475213

RESUMO

The bacterial mechanosensitive channel of small conductance (MscS) has been extensively studied to understand how mechanical forces are converted into the conformational changes that underlie mechanosensitive (MS) channel gating. We showed that lipid removal by ß-cyclodextrin can mimic membrane tension. Here, we show that all cyclodextrins (CDs) can activate reconstituted Escherichia coli MscS, that MscS activation by CDs depends on CD-mediated lipid removal, and that the CD amount required to gate MscS scales with the channel's sensitivity to membrane tension. Importantly, cholesterol-loaded CDs do not activate MscS. CD-mediated lipid removal ultimately causes MscS desensitization, which we show is affected by the lipid environment. While many MS channels respond to membrane forces, generalized by the "force-from-lipids" principle, their different molecular architectures suggest that they use unique ways to convert mechanical forces into conformational changes. To test whether CDs can also be used to activate other MS channels, we chose to investigate the mechanosensitive channel of large conductance (MscL) and demonstrate that CDs can also activate this structurally unrelated channel. Since CDs can open the least tension-sensitive MS channel, MscL, they should be able to open any MS channel that responds to membrane tension. Thus, CDs emerge as a universal tool for the structural and functional characterization of unrelated MS channels.

3.
Commun Biol ; 4(1): 1038, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489534

RESUMO

Mechanosensitive channels are integral membrane proteins that sense mechanical stimuli. Like most plasma membrane ion channel proteins they must pass through biosynthetic quality control in the endoplasmic reticulum that results in them reaching their destination at the plasma membrane. Here we show that N-linked glycosylation of two highly conserved asparagine residues in the 'cap' region of mechanosensitive Piezo1 channels are necessary for the mature protein to reach the plasma membrane. Both mutation of these asparagines (N2294Q/N2331Q) and treatment with an enzyme that hydrolyses N-linked oligosaccharides (PNGaseF) eliminates the fully glycosylated mature Piezo1 protein. The N-glycans in the cap are a pre-requisite for N-glycosylation in the 'propeller' regions, which are present in loops that are essential for mechanotransduction. Importantly, trafficking-defective Piezo1 variants linked to generalized lymphatic dysplasia and bicuspid aortic valve display reduced fully N-glycosylated Piezo1 protein. Thus the N-linked glycosylation status in vitro correlates with efficient membrane trafficking and will aid in determining the functional impact of Piezo1 variants of unknown significance.

4.
IEEE Trans Vis Comput Graph ; 27(11): 4087-4096, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34449378

RESUMO

A common approach for Augmented Reality labeling is to display the label text on a flag planted into the real world element at a 3D anchor point. When there are more than just a few labels, the efficiency of the interface decreases as the user has to search for a given label sequentially. The search can be accelerated by sorting the labels alphabetically, but sorting all labels results in long and intersecting leader lines from the anchor points to the labels. This paper proposes a partially-sorted concentric label layout that leverages the search efficiency of sorting while avoiding the label display problems of long or intersecting leader lines. The labels are partitioned into a small number of sorted sequences displayed on circles of increasing radii. Since the labels on a circle are sorted, the user can quickly search each circle. A tight upper bound derived from circular permutation theory limits the number of circles and thereby the complexity of the label layout. For example, 12 labels require at most three circles. When the application allows it, the labels are presorted to further reduce the number of circles in the layout. The layout was tested in a user study where it significantly reduced the label searching time compared to a conventional single-circle layout.

5.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200949

RESUMO

In this paper, carbon/zinc oxide (LC/ZnO) composites were successfully synthesized and characterized by X-ray powder diffraction, field emission scanning electron microscopy, Fourier transform infrared spectroscopy, Raman, thermogravimetry, and N2 adsorption-desorption, and tested by electrochemical performance. Studies have shown that the morphology of LC/ZnO composites is that lignin pellets are embedded in ZnO microplates. The lignin carbon in the composites mainly exists in an amorphous structure, and the specific surface area and pore channels of metal oxides are increased by the presence of lignin carbon. The electrochemical performance test shows that the carbonization temperature of LC/ZnO with the highest specific capacitance is 550 °C, and the capacitance retention rate reaches 96.74% after 1000 cycles of testing, indicating that the composite material has good cycle stability. Compared with the control group, it is found that the specific capacitance of LC/ZnO-550 °C is 2.3 times and 1.8 times that of ZnO-550 °C and LC-550 °C, respectively. This shows that during the electrochemical test, the lignin carbon and the metal oxide promote each other and act synergistically. In addition, the composite material exhibits the characteristics of a pseudo-capacitance capacitor, indicating that the redox reaction occurred in the electrochemical performance test.

6.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299234

RESUMO

Brassinosteroids (BRs) are known to be essential regulators for wood formation in herbaceous plants and poplar, but their roles in secondary growth and xylem development are still not well-defined, especially in pines. Here, we treated Pinus massoniana seedlings with different concentrations of exogenous BRs, and assayed the effects on plant growth, xylem development, endogenous phytohormone contents and gene expression within stems. Application of exogenous BR resulted in improving development of xylem more than phloem, and promoting xylem development in a dosage-dependent manner in a certain concentration rage. Endogenous hormone determination showed that BR may interact with other phytohormones in regulating xylem development. RNA-seq analysis revealed that some conventional phenylpropanoid biosynthesis- or lignin synthesis-related genes were downregulated, but the lignin content was elevated, suggesting that new lignin synthesis pathways or other cell wall components should be activated by BR treatment in P. massoniana. The results presented here reveal the foundational role of BRs in regulating plant secondary growth, and provide the basis for understanding molecular mechanisms of xylem development in P. massoniana.


Assuntos
Brassinosteroides/farmacologia , Pinus/metabolismo , Xilema/metabolismo , Brassinosteroides/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Lignina/metabolismo , Floema/efeitos dos fármacos , Floema/metabolismo , Pinus/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Madeira/genética , Xilema/efeitos dos fármacos , Xilema/crescimento & desenvolvimento
8.
Brain Behav ; 11(8): e2242, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34105901

RESUMO

Among many of the autoimmune diseases observed in patients with myasthenia gravis (MG), myocarditis is one of the most critical. The goal of this review is to systematically describe and investigate the characteristics of MG complicated with myocarditis. We identified 183 records in PubMed (MEDLINE), Web of Science, and EMBASE from 1948 to September 10, 2020. Studies were included if they presented clinical data on MG complicated with myocarditis. Of the 35 patients from 28 studies in this review, 57.14% (20/35) were males, with a mean age of 59.11 ± 15.87. Dyspnea was the most common cardiac symptom accounting for over 60% in the study. Among the 35 patients, 13 cases of myocarditis occurred concomitantly with MG and the longest interval between MG and myocarditis was 7 years. Forty percent of patients developed myocarditis caused by immune checkpoint inhibitors (ICI). Among the patients with myocarditis, over half of the patients were diagnosed by myocardial biopsy. After active immune regulation and symptomatic treatment, only 15 of 35 patients with MG complicated with myocarditis improved, 18 patients died during hospitalization, one patient died due to tumor progression and 1patient died 5 years later. The prognosis of patients with MG complicated with myocarditis is poor, and myocardial enzymes and other indexes need to be monitored for patients taking ICI drugs. Patients with dyspnea who are still not ideally treated by mechanical ventilation should be vigilant against the occurrence of MG complicated with myocarditis.


Assuntos
Miastenia Gravis , Miocardite , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Miocardite/complicações , Miocardite/tratamento farmacológico
9.
J Biol Chem ; 296: 100738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33957127

RESUMO

Anoctamin-1 (ANO1) (TMEM16A) is a calcium-activated chloride channel that plays critical roles in diverse physiological processes, such as sensory transduction and epithelial secretion. ANO1 levels have been shown to be altered under physiological and pathological conditions, although the molecular mechanisms that control ANO1 protein levels remain unclear. The ubiquitin-proteasome system is known to regulate the levels of numerous ion channels, but little information is available regarding whether and how ubiquitination regulates levels of ANO1. Here, we showed that two E3 ligases, TRIM23 and TRIM21, physically interact with the C terminus of ANO1. In vitro and in vivo assays demonstrated that whereas TRIM23 ubiquitinated ANO1 leading to its stabilization, TRIM21 ubiquitinated ANO1 and induced its degradation. Notably, ANO1 regulation by TRIM23 and TRIM21 is involved in chemical-induced pain sensation, salivary secretion, and heart-rate control in mice, and TRIM23 also mediates ANO1 upregulation induced by epidermal growth factor treatment. Our results suggest that these two antagonistic E3 ligases act together to control ANO1 expression and function. Our findings reveal a previously unrecognized mechanism for regulating ANO1 protein levels and identify a potential molecular link between ANO1 regulation, epidermal growth factor, and other signaling pathways.


Assuntos
Anoctamina-1/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Neoplasias/metabolismo , Ribonucleoproteínas/metabolismo , Células HEK293 , Humanos , Estabilidade Proteica , Proteólise , Ubiquitinação
10.
Int J Environ Health Res ; : 1-11, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825597

RESUMO

This study was to investigate the effects of oxidative stress in cigarette smoke (CS)-induced cell apoptosis in mice with emphysema. Thirty-two mice were divided into four groups: the control group, the CS group, the CS + Pifithrin-α group, and the CS + NAC group. Pathological changes and apoptosis in lung tissue of mice were detected. The activity of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were measured using spectrophotometer. The proteins expression of p53, Bcl-2, Bax, and caspase-3 were determined by western blot. The results showed that cell apoptosis, lung structural damage, and the activity of MDA, as well as the expression of apoptosis-related proteins Bax, total caspase-3, and cleaved caspase-3 were increased in CS-treated mice. The activity of SOD, CAT, and T-AOC, as well as the expression of anti-apoptosis protein Bcl-2 were decreased in CS-treated mice when compared with the control group. However, Pifithrin-α (p53 inhibitor) and N-Acetylcysteine (NAC) could reduce cell apoptosis, lung structural damage and oxidative stress, accelerate the expression of Bcl-2, while suppressing the expression of Bax, total caspase-3 and cleaved caspase-3. More importantly, the treatment with NAC even inhibited the expression of p53. In conclusions, oxidative stress linking the p53 is involved in cell apoptosis in CS-treated emphysema mice.

11.
eNeuro ; 8(1)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33509951

RESUMO

The mechanotransduction (MT) complex in auditory hair cells converts the mechanical stimulation of sound waves into neural signals. Recently, the MT complex has been suggested to contain at least four distinct integral membrane proteins: protocadherin 15 (PCDH15), transmembrane channel-like protein 1 (TMC1), lipoma HMGIC fusion partner-like 5 (LHFPL5), and transmembrane inner ear protein (TMIE). However, the composition, function, and regulation of the MT-complex proteins remain incompletely investigated. Here, we report previously undescribed splicing isoforms of TMC1, LHFPL5, and TMIE. We identified four alternative splicing events for the genes encoding these three proteins by analyzing RNA-seq libraries of auditory hair cells from adult mice [over postnatal day (P)28], and we then verified the alternative splicing events by using RT-PCR and Sanger sequencing. Moreover, we examined the tissue-specific distribution, developmental expression patterns, and tonotopic gradient of the splicing isoforms by performing semiquantitative and quantitative real-time PCR (qRT-PCR), and we found that the alternative splicing of TMC1 and LHFPL5 is cochlear-specific and occurs in both neonatal and adult mouse cochleae. Our findings not only reveal the potential complexity of the MT-complex composition, but also provide critical insights for guiding future research on the function, regulation, and trafficking of TMC1, LHFPL5, and TMIE and on the clinical diagnosis of hearing loss related to aberrant splicing of these three key genes in hearing.


Assuntos
Processamento Alternativo , Mecanotransdução Celular , Proteínas de Membrana/genética , Animais , Cóclea , Células Ciliadas Auditivas , Audição , Camundongos
12.
Int J Chron Obstruct Pulmon Dis ; 15: 2449-2460, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116460

RESUMO

Background and Objectives: Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of many diseases, including cancer, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In this study, we intended to identify the differentially expressed lncRNAs and the role of HOXA cluster antisense RNA 2 (HOXA-AS2) in patients with COPD. Methods: We analyzed lncRNA profiles of three non-COPD and seven COPD patients' lungs via microarray and then validated the expression of the top differentially expressed lncRNAs by using real-time polymerase chain reaction (PCR). To identify the mechanism of HOXA-AS2 during COPD pathogenesis and endothelial cell proliferation, we knocked down and overexpressed HOXA-AS2 with siRNA and lentivirus transfection approach in human pulmonary microvascular endothelial cells (HPMECs). Results: Among 29,150 distinct lncRNA transcripts, 353 lncRNAs were significantly (≥2-fold change and P<0.05) upregulated and 552 were downregulated in COPD patients. The fold change of HOXA-AS2 is 9.32; real-time PCR confirmed that HOXA-AS2 was downregulated in COPD patients. In in vitro experiments, cigarette smoke extract (CSE) treatment reduced the expression of HOXA-AS2 and cell proliferation of HPMECs. Knocking down HOXA-AS2 inhibited HPMECs proliferation and the expression of Notch1 in HPMECs. Overexpressing Notch1 could partly rescue the inhibition of cell viability induced by the silence of HOXA-AS2. Conclusion: Our results demonstrated that differentially expressed lncRNAs may act as potential molecular biomarkers for the diagnosis of COPD, and HOXA-AS2 was involved in the pathogenesis of COPD by regulating HPMECs proliferation via Notch1, which may provide a new approach for COPD treatment.


Assuntos
Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células , Células Endoteliais , Humanos , Pulmão , Análise em Microsséries , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , RNA Longo não Codificante/genética , Receptor Notch1/genética
13.
Int J Chron Obstruct Pulmon Dis ; 15: 2257-2266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061343

RESUMO

Background: Fractional exhaled nitric oxide (FENO) has been shown to be a marker of airway inflammation in various pulmonary diseases, including chronic obstructive pulmonary disease (COPD). In this study, we assessed the FENO level in patients with acute exacerbations of COPD (AECOPD) and analyzed the predictive value of the FENO level for treatment response. Methods: Demographic data were collected at admission. FENO, lung function, blood gases, COPD Assessment Test (CAT), and modified Medical Research Council (mMRC) scores were measured at admission and on day 7. At the second visit, the patients were asked to report their health status; scores ranged from 1 to 5, representing "much better", "slightly better", "no change", "slightly worse", and "much worse", respectively. The treatment response was evaluated based on the patient's reported health status (responders were those who reported much better and slightly better) and lung function (responders were those who presented an increase in FEV1 over 200 mL). Results: A total of 182 patients were recruited into the analysis. The FENO level positively correlated with an increase in FEV1 and FEV1% (r = 0.291, p < 0.001 and r = 0.205, p = 0.005, respectively), but negatively correlated with a decrease in the COPD Assessment Test (CAT) score (r = -0.197, p = 0.008) and patient-reported health status (rho = -0.408, p<0.001). An inverse correlation was observed between FENO concentrations at admission and the length of hospital stay. The cut-off point for differentiating responders, identified by health status, was 18 ppb, with the sensitivity being 89.7% and specificity 88.9%. Conclusion: FENO levels, determined at hospital admission, are potential to predict the overall treatment response in AECOPD patients, including remission in subjective patient-reported health statuses and, also, improvements in lung function. Registry Number: ChiCTR-ROC-16,009,087 (http://www.chictr.org.cn/).


Assuntos
Óxido Nítrico , Doença Pulmonar Obstrutiva Crônica , Testes de Função Respiratória , Idoso , Biomarcadores , Expiração , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
14.
Int J Chron Obstruct Pulmon Dis ; 15: 1613-1619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753861

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD), usually caused by tobacco smoking, is increased in China. Smoking cessation is the first step in COPD management. Data on predictors of smoking cessation are sparse in COPD patients in China. We aim to find the differences in the clinical characteristics between ex-smokers and current smokers with COPD to determine the factors related to smoking cessation. Patients and Methods: From outpatient departments of 12 hospitals in Hunan and Guangxi provinces, a total of 4331 patients were included. Information on demographic and sociological data, lung function, and modified Medical Research Council (mMRC) dyspnea scale scores were recorded. Patients were divided into an ex-smokers group and a current smokers group based on whether they gave up smoking. A logistic regression analysis was performed to analyze the factors associated with smoking cessation. Results: Of the total, the mean age was 62.9±8.5 years, and 47.3% were ex-smokers. Compared with the current smokers, the ex-smokers were older, and had heavier dyspnea, more severe airflow limitation, fewer pack-years, shorter smoking duration, and a higher proportion of Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups C and D. The logistic regression model showed that smoking cessation was negatively correlated with widowhood, years of smoking, and forced expiratory volume in 1 second (FEV1), but was positively correlated with age, education level, amount smoked, mMRC score, GOLD grades, and GOLD groups. Conclusion: Among patients with COPD, more than half still smoked. In the group of patients who quit smoking, many of them quit rather late in age after they had significant symptoms. Several predictors of smoking cessation were identified, indicating that ex-smokers differ substantially from continuing smokers. This should be taken into account in smoking-cessation interventions.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Fumantes , Idoso , China/epidemiologia , Estudos Transversais , Ex-Fumantes , Volume Expiratório Forçado , Humanos , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia
15.
Respiration ; 99(7): 606-616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32659763

RESUMO

BACKGROUND: The Clinical COPD Questionnaire (CCQ) has been suggested by the Global Initiative of Chronic Obstructive Lung Disease (GOLD) as a comprehensive symptom measurement tool, which helps to classify patients in order to direct pharmacological treatment. Therefore, it is essential to understand its determinants. OBJECTIVES: To identify the determinants of the overall CCQ score and scores of its 3 subdomains among chronic obstructive pulmonary disease (COPD) patients from China. METHODS: A total of 1,241 COPD patients in the outpatient department of the Second Xiangya Hospital in China were recruited. Basic information and clinical data were collected. Differences in the GOLD categories based on Modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), and CCQ were compared. Multiple linear regression analyses were performed to evaluate determinant factors of the total CCQ and subdomain scores. RESULTS: The total CCQ and/or separate domain scores significantly differed with sex, age, BMI, smoking status, biomass fuel exposure, exacerbation frequency, mMRC, CAT, and GOLD grades and groups. Subjects with asthma-COPD overlap (ACO) had worse health status based on CCQ than those with COPD alone. As for the 16 subgroups based on GOLD 2017, statistical differences in the total CCQ and functional domain scores were found among subgroups 1A-4A, 1B-4B, and 1D-4D. The mMRC classified much more patients into more symptom groups than CAT and CCQ. No significant difference was observed in the GOLD categories between the CAT and CCQ (cut point = 1.5). Multiple linear regression analysis showed that smoking status, underweight, ACO, post-bronchodilator FEV1% predicted <50%, exacerbation history, and mMRC were independently associated with the total CCQ score. Only 3 variables were significantly associated with the symptom domain: ACO, exacerbations, and mMRC; for the functional domain, age ≥75 years, ACO, post-bronchodilator FEV1% predicted <50%, exacerbation history, and mMRC were significant; female sex, underweight, frequent exacerbations (≥2), and mMRC were significantly associated with higher scores in the mental domain. CONCLUSIONS: The classification of COPD produced by mMRC, CAT, and CCQ was not identical. Smoking status, underweight, ACO, post-bronchodilator FEV1% predicted <50%, exacerbation history, and mMRC were associated with lower health-related quality of life assessed by the total CCQ score, while different subdomains of CCQ had different determinant factors.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
16.
Cell Rep ; 30(10): 3323-3338.e6, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32160540

RESUMO

Eukaryotic DNA replication licensing is a prerequisite for, and plays a role in, regulating genome duplication that occurs exactly once per cell cycle. ORC (origin recognition complex) binds to and marks replication origins throughout the cell cycle and loads other replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs), completing replication licensing. However, how an asymmetric single-heterohexameric ORC structure loads the symmetric MCM (minichromosome maintenance) double hexamers is controversial, and importantly, it remains unknown when and how ORC proteins associate with the newly replicated origins to protect them from invasion by histones. Here, we report an essential and cell-cycle-dependent ORC "dimerization cycle" that plays three fundamental roles in the regulation of DNA replication: providing a symmetric platform to load the symmetric pre-RCs, marking and protecting the nascent sister replication origins for the next licensing, and playing a crucial role to prevent origin re-licensing within the same cell cycle.


Assuntos
Ciclo Celular , Cromossomos Fúngicos/metabolismo , Replicação do DNA , Dimerização , Origem de Replicação , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Proliferação de Células , Cromatina/metabolismo , Modelos Biológicos , Mutação/genética , Fosforilação , Subunidades Proteicas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
17.
Carbohydr Res ; 491: 107986, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32222490

RESUMO

Carbon aerogels are 3D hierarchical multiscale porous materials with outstanding physicochemical properties such as high specific surface area, low density, high porosity, excellent electrical conductor, good chemical stability, hydrophobicity, and adjustable surface chemistry among others. Unlike conventional carbon aerogels, biomass-based carbon aerogels are economical, environmentally friendly and have nigh inexhaustible precursors, which have generated extensive interest and exhibited outstanding electrocatalysis and adsorption/absorption performance. In this review, we mainly summarized the four main kinds of biomass (cellulose, chitosan, lignin and tannin) as carbon aerogel precursor, and discussed in detail their resource, constitute and optimized synthesis mechanism. Further advice was also given for better utilization of biomass as carbon aerogel precursors.


Assuntos
Carbono/química , Celulose/síntese química , Quitosana/síntese química , Taninos/síntese química , Biomassa , Celulose/química , Quitosana/química , Géis/síntese química , Géis/química , Tamanho da Partícula , Propriedades de Superfície , Taninos/química
18.
JCI Insight ; 5(3)2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31935199

RESUMO

Alternative polyadenylation (APA) is a widespread and important mechanism in regulation of gene expression. Dysregulation of the 3' UTR cleavage and polyadenylation represents a common characteristic among many disease states, including lung fibrosis. In this study, we investigated the role of mammalian cleavage factor I-mediated (CFIm-mediated) APA in regulating extracellular matrix production in response to mechanical stimuli from stiffened matrix simulating the fibrotic lungs. We found that stiff matrix downregulated expression of CFIm68, CFIm59 and CFIm25 subunits and promoted APA in favor of the proximal poly(A) site usage in the 3' UTRs of type I collagen (COL1A1) and fibronectin (FN1) in primary human lung fibroblasts. Knockdown and overexpression of each individual CFIm subunit demonstrated that CFIm68 and CFIm25 are indispensable attributes of stiff matrix-induced APA and overproduction of COL1A1, whereas CFIm did not appear to mediate stiffness-regulated FN1 APA. Furthermore, expression of the CFIm subunits was associated with matrix stiffness in vivo in a bleomycin-induced mouse model of pulmonary fibrosis. These data suggest that stiff matrix instigates type I collagen biogenesis by selectively targeting mRNA transcripts for 3' UTR shortening. The current study uncovered a potential mechanism for regulation of the CFIm complex by mechanical cues under fibrotic conditions.


Assuntos
Colágeno Tipo I/biossíntese , Poli A/metabolismo , Regiões 3' não Traduzidas , Animais , Células Cultivadas , Regulação para Baixo , Regulação da Expressão Gênica , Humanos , Mamíferos , RNA Mensageiro/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-31936453

RESUMO

Chinese windmill palms (Trachycarpus fortunei) are widely planted in karst bedrock outcrop areas in southwest China because of their high economic and ecological values. The aims of this study were to investigate the foraging ability of Chinese windmill palm seedlings planted in six different types of karst microhabitat and to identify the main environmental factors that influence root foraging ability. We planted three-year-old Chinese windmill palm seedlings in six typical karst microhabitats (i.e., rocky trough, rocky surface, rocky gully, rocky soil surface, rocky pit, and soil surface microhabitats). One year after transplanting, the seedlings were excavated to determine the morphological parameters values of new roots and the nutrient concentrations of new roots and leaves. The root foraging ability of Chinese windmill palm seedlings, defined as new root length and new root surface area, was significantly greater in the rocky trough, rocky soil surface, and soil surface microhabitats than in the rocky gully, rocky surface, and rocky pit microhabitats (p < 0.05). Redundancy analysis revealed that the main positive factor affecting the rooting ability of Chinese windmill palm seedlings was soil thickness. Chinese windmill palm seedlings improved their root absorption efficiency by increasing their root length and root surface area under soil nutrient deficiency conditions. The organic carbon, total nitrogen, and available potassium in soil positively influenced the concentration of N and K in roots. Total potassium in soil negatively influenced the biomass of new annual leaves and concentrations of N, P and K in new annual roots and leaves. Chinese windmill palm seedlings can be grown in the different karst microhabitats, especially in the rocky trough, rocky soil surface, and soil surface microhabitats, and, therefore, it is suitable for use in the regeneration of karst forests.


Assuntos
Arecaceae/fisiologia , Florestas , Raízes de Plantas/fisiologia , Solo , Biomassa , China , Ecologia , Nitrogênio , Folhas de Planta , Plantas , Plântula
20.
COPD ; 17(1): 90-100, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31948299

RESUMO

The purposes of this study were to: (1) study the prevalence of pain in patients with mild-to-very severe chronic obstructive pulmonary disease (COPD) in China; (2) compare the differences in pain characteristics between stable COPD and acute exacerbation of COPD (AECOPD); (3) explore the clinical associations with pain in those with COPD. This cross-sectional study was conducted in China from October 24, 2017, to January 11, 2019. A face-to-face interview was conducted to collect data. The Chinese version of the brief pain inventory (BPI-C) was applied to investigate the pain characteristics in patients with COPD. Of the 901 patients in this study, 226 (25.1%) patients reported pain problems. The prevalence of pain in patients with mild to very severe COPD was 32.9%, 23.9%, 25.2%, and 23.5%, respectively (p = 0.447). According to the BPI-C results, 31.3% (31/99) of patients reported pain of AECOPD, compared to 24.3% (195/802) of stable COPD (p = 0.13). Reported pain intensity and pain interference evaluated by the BPI-C were significantly higher in AECOPD than stable COPD (p < 0.001, p < 0.05, respectively). Those with body mass index (BMI) ≥ 24kg/m2 or COPD assessment test (CAT) score > 20 were significantly more likely to have pain problems than BMI < 24kg/m2 (aOR = 1.568, a95IC = 1.132-2.170, p = 0.007) or CAT ≤ 20 (aOR= 1.754, a95IC = 1.213-2.536, p = 0.003). Pain was common in patients with both stable COPD and AECOPD. AECOPD patients had a significantly higher pain intensity than stable COPD. Overweight and CAT > 20 were significantly related to higher prevalence of pain.


Assuntos
Dor/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , China/epidemiologia , Comorbidade , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Medição da Dor , Prevalência , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Espirometria
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...