Publications by authors named "Zijing Zhou"

31 Publications

A systematic review of myasthenia gravis complicated with myocarditis.

Brain Behav 2021 Jun 9. Epub 2021 Jun 9.

Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

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.
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http://dx.doi.org/10.1002/brb3.2242DOI Listing
June 2021

Opposing roles of E3 ligases TRIM23 and TRIM21 in regulation of ion channel ANO1 protein levels.

J Biol Chem 2021 May 3:100738. Epub 2021 May 3.

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong; Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong; State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong; HKUST Shenzhen Research Institute, Hong Kong University of Science and Technology, Hong Kong; Hong Kong Branch of Guangdong Southern Marine Science and Engineering Laboratory (Guangzhou), Hong Kong University of Science and Technology, Hong Kong. Electronic address:

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 (EGF) 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, EGF, and other signaling pathways.
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http://dx.doi.org/10.1016/j.jbc.2021.100738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191318PMC
May 2021

Alternative Splicing of Three Genes Encoding Mechanotransduction-Complex Proteins in Auditory Hair Cells.

eNeuro 2021 Jan-Feb;8(1). Epub 2021 Feb 23.

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China

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.
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http://dx.doi.org/10.1523/ENEURO.0381-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920537PMC
June 2021

The Value of FENO Measurement for Predicting Treatment Response in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 24;15:2257-2266. Epub 2020 Sep 24.

Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China.

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 FEV over 200 mL).

Results: A total of 182 patients were recruited into the analysis. The FENO level positively correlated with an increase in FEV and FEV% (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/).
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http://dx.doi.org/10.2147/COPD.S263673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522317PMC
September 2020

Different Characteristics of Ex-Smokers and Current Smokers with COPD: A Cross-Sectional Study in China.

Int J Chron Obstruct Pulmon Dis 2020 7;15:1613-1619. Epub 2020 Jul 7.

Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University; Research Unit of Respiratory Disease, Central South University; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha 410011, Hunan, People's Republic of China.

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.
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http://dx.doi.org/10.2147/COPD.S255028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354950PMC
July 2020

Determinants of Clinical COPD Questionnaire in Patients with COPD: A Cross-Sectional Observational Study.

Respiration 2020;99(7):606-616. Epub 2020 Jul 13.

Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Research Unit of Respiratory Disease, Central South University, Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, China,

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.
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http://dx.doi.org/10.1159/000507097DOI Listing
July 2020

Synthesis of biomass-based carbon aerogels in energy and sustainability.

Carbohydr Res 2020 May 20;491:107986. Epub 2020 Mar 20.

School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.carres.2020.107986DOI Listing
May 2020

An Essential and Cell-Cycle-Dependent ORC Dimerization Cycle Regulates Eukaryotic Chromosomal DNA Replication.

Cell Rep 2020 03;30(10):3323-3338.e6

Division of Life Science, Center for Cancer Research, and State Key Lab of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; The First Clinical Medicine College, Guangzhou University of Chinese Medicine, Guangzhou, China; EnKang Pharmaceuticals Limited, Guangzhou, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.celrep.2020.02.046DOI Listing
March 2020

Prevalence and Characteristics of Pain in Patients of Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study in China.

COPD 2020 02 17;17(1):90-100. Epub 2020 Jan 17.

Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China.

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 ( 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 ( 0.13). Reported pain intensity and pain interference evaluated by the BPI-C were significantly higher in AECOPD than stable COPD ( < 0.001,  < 0.05, respectively). Those with body mass index (BMI) ≥ 24kg/m or COPD assessment test (CAT) score > 20 were significantly more likely to have pain problems than BMI < 24kg/m (aOR = 1.568, a95IC = 1.132-2.170,  = 0.007) or CAT ≤ 20 (aOR= 1.754, a95IC = 1.213-2.536,  = 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.
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http://dx.doi.org/10.1080/15412555.2020.1713076DOI Listing
February 2020

Influence of Heterogeneous Karst Microhabitats on the Root Foraging Ability of Chinese Windmill Palm () Seedlings.

Int J Environ Res Public Health 2020 01 9;17(2). Epub 2020 Jan 9.

College of Forestry, Guizhou University, Guiyang 550025, China.

Chinese windmill palms () 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 ( < 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.
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http://dx.doi.org/10.3390/ijerph17020434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014210PMC
January 2020

Stiff matrix instigates type I collagen biogenesis by mammalian cleavage factor I complex-mediated alternative polyadenylation.

JCI Insight 2020 02 13;5(3). Epub 2020 Feb 13.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

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.
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http://dx.doi.org/10.1172/jci.insight.133972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098798PMC
February 2020

Prospective development of practical screening strategies for diagnosis of asthma-COPD overlap.

Respirology 2020 07 27;25(7):735-742. Epub 2019 Nov 27.

Department of Respiratory and Critical Care Medicine, Second Xiangya Hospital, Central South University, Changsha, China.

Background And Objective: ACO is a syndrome with high prevalence. However, a pragmatic diagnostic criterion to differentiate ACO is non-existent. We aimed to establish an effective model for screening ACO.

Methods: A multicentre survey was developed to assess the clinical criteria considered important and applicable by pulmonologists for screening ACO. These experts were asked to take the surveys twice. The expert grading method, analytic hierarchy process and ROC curve were used to establish the model, which was then validated by a cross-sectional study of 1066 patients. The GINA/GOLD document was the gold standard in assessing this model.

Results: Increased variability of symptoms, paroxysmal wheezing, dyspnoea, historical diagnosis of COPD or asthma, allergic constitution, exposure to risk factors, the FEV /FVC < 70% and a positive BDT were important for screening ACO. According to the weight of each criterion, we confirmed that patients meeting six or more of these eight criteria should be considered to have ACO. We called this Chinese screening model for ACO 'CSMA'. It differentiated patients with ACO with a sensitivity of 83.33%, while the sensitivity of clinician-driven diagnosis had a sensitivity of only 42.73%.

Conclusion: CSMA is a workable model for screening ACO and provides a simple tool for clinicians to efficiently diagnose ACO.
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http://dx.doi.org/10.1111/resp.13743DOI Listing
July 2020

Calcium in Vascular Smooth Muscle Cell Elasticity and Adhesion: Novel Insights Into the Mechanism of Action.

Front Physiol 2019 7;10:852. Epub 2019 Aug 7.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama-Birmingham, Birmingham, AL, United States.

Vascular smooth muscle cells (VSMCs) are the predominant cell type in the arterial wall. These cells play a critical role in maintaining vascular homeostasis including vasoconstriction and vasodilatation through active contraction and relaxation. Dysregulation of VSMC function alters the response of blood vessels to mechanical stress, contributing to the pathogenesis of vascular diseases, particularly atherosclerosis and hypertension. The stiffness of VSMCs is a major regulator of vascular function. Previous studies suggest that intracellular Ca controls the stiffness of VSMCs by a mechanism involving myosin contractile apparatus. More recent studies highlight important functions of cytoskeletal α-smooth muscle actin (α-SMA), α5β1 integrin, and integrin-mediated cell-extracellular matrix (ECM) interactions in Ca-dependent regulation of VSMC stiffness and adhesion to the ECM, providing novel insights into the mechanism of calcium action.
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http://dx.doi.org/10.3389/fphys.2019.00852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693425PMC
August 2019

Phase-space deconvolution for light field microscopy.

Opt Express 2019 Jun;27(13):18131-18145

Light field microscopy, featuring with snapshot large-scale three-dimensional (3D) fluorescence imaging, has aroused great interests in various biological applications, especially for high-speed 3D calcium imaging. Traditional 3D deconvolution algorithms based on the beam propagation model facilitate high-resolution 3D reconstructions. However, such a high-precision model is not robust enough for the experimental data with different system errors such as optical aberrations and background fluorescence, which bring great periodic artifacts and reduce the image contrast. In order to solve this problem, here we propose a phase-space deconvolution method for light field microscopy, which fully exploits the smoothness prior in the phase-space domain. By modeling the imaging process in the phase-space domain, we convert the spatially-nonuniform point spread function (PSF) into a spatially-uniform one with a much smaller size. Experiments on various biological samples and resolution charts are demonstrated to verify the contrast enhancement with much fewer artifacts and 10-times less computational cost by our method without any hardware modifications required.
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http://dx.doi.org/10.1364/OE.27.018131DOI Listing
June 2019

Landscape Grain Effect in Yancheng Coastal Wetland and Its Response to Landscape Changes.

Int J Environ Res Public Health 2019 06 24;16(12). Epub 2019 Jun 24.

Department of Geography & Spatial Information Techniques, Ningbo University, Ningbo 315211, China.

The landscape grain effect reflects the spatial heterogeneity of a landscape and it is used as a research core of landscape ecology. The landscape grain effect can be used to not only explore spatiotemporal variation characteristics of a landscape pattern, but also to disclose variation laws of ecological structures and functions of landscapes. In this study, the sensitivity of landscape pattern indexes to grain sizes 50-1000 m was studied based on landscape data in Yancheng Coastal Wetland acquired in 1991, 2000, 2008, and 2017. Response of the grain effect to landscape changes was analyzed and an optimal grain size for analysis in the study area was determined. Results indicated that: (1) among 27 indexes (12 in a class level and 15 in a landscape level), eight indexes were highly sensitive to grains, ten indexes presented moderate sensitivity, eight indexes presented low sensitivity, and one was unresponsive. It was shown that the area-margin index and the shape index were more sensitive to the different grain sizes. The aggregation index had some differences in the grain size change, and the diversity index had a low response degree to the grain size. (2) Landscape indexes showed six different responses to different grains, including slow reduced response, fast reduced and then slow reduced response, monotonically increased response, fluctuating reduced response, up-down responses, and stable response, which indicated that the landscape index was closely related to the spatial grain. (3) From 1991 to 2017, variation curves of the landscape grain size of different landscape types could be divided into four types: fluctuation rising type, fluctuation type, monotonous decreasing type, and monotonous rising type. Different grain size curves had different interpretations of landscape changes, but in general, Yancheng Coastal Wetland's landscape tended to be fragmented and complicated, internal connectivity was weakened, and dominant landscape area was reduced. Natural wetlands were more sensitive to grain size effects than artificial wetlands. (4) The landscape index at the 50 m grain size had a strong response to different grain size changes, and the loss of landscape information was the smallest. Therefore, it was determined that the optimal landscape grain size in the study area was 50 m.
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http://dx.doi.org/10.3390/ijerph16122225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616968PMC
June 2019

An overview of fungal glycan-based therapeutics.

Prog Mol Biol Transl Sci 2019 21;163:135-163. Epub 2019 Mar 21.

Systems Biology and Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Edible medicinal mushrooms have been traditionally used for health promotion and longevity in China and other East Asian countries for centuries. Structural and pharmacological studies revealed that fungal glycans show multiple physiological and healthy promoting effects including immunomodulation, anti-tumor, anti-aging, anti-oxidation, hypoglycemic, hypolipidemic, anti-radiation, and other effects. Fungal glycans isolated from different kinds of medicinal mushrooms are partially purified and clinically tested. Without serious safety concerns of mostly glycans from edible mushrooms and/or the cultured mycelium, eight of them are approved by Chinese Food and Drug Administration (SFDA) and used clinically in China since 1980s. In this chapter, 185 independent studies involving in biochemical, pharmacological and clinical studies of fungal glycans during the past four decades (1977-2019) from PubMed, CNKI (China National Knowledge Infrastructure) and Wanfang databases are summarized. In future, understanding the fungal glycan-based drugs at molecular biological level would be needed to comprehend the clinical efficacy of glycan-based drugs.
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http://dx.doi.org/10.1016/bs.pmbts.2019.02.001DOI Listing
February 2020

The role of CAT in evaluating the response to treatment of patients with AECOPD.

Int J Chron Obstruct Pulmon Dis 2018 11;13:2849-2858. Epub 2018 Sep 11.

Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China,

Background: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) questionnaire is a short patient-completed questionnaire, which is used to assess the health status of patients with stable COPD. However, whether it is a good tool to evaluate the response to treatment in acute exacerbation of COPD (AECOPD) has been less studied.

Methods: The patients were assessed at two visits, at admission and on the seventh day. Anthropometric variables were collected at admission. CAT and lung function were measured twice at the above time points. At the second visit, the health status of the patients were divided into five groups based on a 5-point Likert scale, ranging from 1 to 5, which represents "much better," "slightly better," "no change," "slightly worse," and "much worse." Responders were those who reported "much better" or "slightly better," and nonresponders were those who claimed "no change," "worse," or "much worse."

Results: In total, 225 patients were recruited. The average CAT score at admission was 24.82±7.41, which declined to 17.41±7.35 on the seventh day. There were 81.33% responders, whose improvement in CAT score (9.37±5.24) was much higher than that of the nonresponders (-1.36±4.35). A moderate correlation was observed between the changes in CAT score and improvement in FEV, FEV%, and the length of hospital stay. There was a strong correlation between the changes in CAT score and health status. A 3.5-unit improvement in the CAT score, with highest area under the curve, was the cutoff to differentiate responders from nonresponders.

Conclusion: The evolution of CAT scores during exacerbation can provide useful information to assess the health status of patients with AECOPD. A 3.5-unit improvement in CAT score is the best cutoff to differentiate between patients who have a response or no response to treatment, which offers a convenient and easy way for clinicians to monitor the health status of patients with an AECOPD.
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http://dx.doi.org/10.2147/COPD.S175085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138970PMC
January 2019

Reversing Mechanoinductive DSP Expression by CRISPR/dCas9-mediated Epigenome Editing.

Am J Respir Crit Care Med 2018 09;198(5):599-609

1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Rationale: DSP (desmoplakin), the most abundant component of desmosomes, which maintain the mechanical integrity of epithelium, is a genome-wide association study-identified genetic risk locus in human idiopathic pulmonary fibrosis (IPF). Subjects with IPF express a significantly higher level of DSP than control subjects.

Objectives: Determine potential mechanisms by which DSP is regulated in lung fibrosis.

Methods: Matrigel-coated soft and stiff polyacrylamide gels were made to simulate the stiffness of normal and fibrotic lungs. Quantitative chromatin immunoprecipitation and electrophoretic mobility shift assay were used to evaluate transcription factor binding to the DSP promoter. Targeted DNA methylation was achieved by CRISPR (clustered regularly interspaced short palindromic repeats)/dCas9 (deactivated CRISPR-associated protein-9 nuclease)-mediated Dnmt3A (DNA methyltransferase 3A) expression under the guidance of sequence-specific single guide RNAs.

Measurements And Main Results: Stiff matrix promotes DSP gene expression in both human and rodent lung epithelial cells as compared with soft matrix. A conserved region in the proximal DSP promoter is hypermethylated under soft matrix conditions and becomes hypomethylated/demethylated under stiff matrix conditions. Demethylation of this conserved DSP promoter region is associated with transactivation of transcription factor EGR1 (early growth response protein 1), resulting in EGR1-dependent DSP overexpression. Targeted DNA methylation by CRISPR/dCas9/Dnmt3A-mediated epigenome editing blocks EGR1 binding to the DSP promoter and inhibits stiff matrix-induced DSP overexpression.

Conclusions: DSP is a matrix stiffness-regulated mechanosensitive gene. CRISPR/dCas9-Dnmt3A-mediated epigenome editing reverses DSP overexpression by reestablishment of the epigenetic control of DSP under the mechanically homeostatic environment. It provides a useful tool for investigations of the functional role of DSP in the pathogenesis of lung fibrosis.
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http://dx.doi.org/10.1164/rccm.201711-2242OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118013PMC
September 2018

A comparison of the assessment of health status between CCQ and CAT in a Chinese COPD clinical population: a cross-sectional analysis.

Int J Chron Obstruct Pulmon Dis 2018 24;13:1675-1682. Epub 2018 May 24.

Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Both the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) were recommended as comprehensive symptom measures by the Global Initiative for Chronic Obstructive Lung disease. The main objective of this work was to compare the evaluation of symptom severity with the CAT and the CCQ and find a cutoff value of the CCQ for the Chinese clinical population.

Methods: Patients diagnosed with stable COPD in the outpatient department who completed the CAT and CCQ were enrolled from November 2015 to December 2016. Scores of 0-10, 11-20, 21-30, and 31-40 represent low, medium, high, and very high impact level, respectively, by CAT. Scores of the CCQ can be considered as acceptable (CCQ<1), acceptable for moderate disease (1≤CCQ<2), instable-severe limited (2≤CCQ<3), and very instable-very severe limited (CCQ≥3).

Results: According to the CAT, only 20.4% of patients belonged to the high (21≤CAT≤30) and very high (31≤CAT≤40) impact levels, which were statistically lower than those of the CCQ, which classified over half of the population (51.1%) into the instable-severe limited (2≤CCQ<3) and very instable-very severe limited (CCQ≥3) categories (<0.001). The kappa of agreement for the symptom groups by CAT and CCQ (cutoff point 1.5) was 0.495, but only slight agreement (0.144) was found between the CAT and CCQ with the cutoff point of 1.0. The CAT and the total CCQ had a strong correlation (rho=0.776, <0.01). The CCQ 1.0 and 1.5 corresponded to CAT 4.2 and 9.7, respectively. The CAT 10.0 was equivalent to 1.53 of the CCQ. In addition, with higher scores of the CAT and CCQ, subjects displayed more impairment in lung function, higher levels on modified Medical Research Council, and higher exacerbation rates in the last year (<0.001). Similarly, patients with more exacerbations presented worse scores on the CAT and total CCQ as well as its 3 domains (<0.001).

Conclusion: Compared with the CAT, the CCQ was more likely to classify the patients into more severe categories, and 1.5 might be a better cutoff point for the CCQ than 1.0. Both the CAT and the overall CCQ with its 3 domains were able to discriminate between groups of patients that differ in COPD severity.
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http://dx.doi.org/10.2147/COPD.S161225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973380PMC
January 2019

α6-Integrin alternative splicing: distinct cytoplasmic variants in stem cell fate specification and niche interaction.

Stem Cell Res Ther 2018 05 2;9(1):122. Epub 2018 May 2.

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Tinsley Harrison Tower 437B, 1900 University Blvd, Birmingham, AL, 35294, USA.

α6-Integrin subunit (also known as CD49f) is a stemness signature that has been found on the plasma membrane of more than 30 stem cell populations. A growing body of studies have focused on the critical role of α6-containing integrins (α6β1 and α6β4) in the regulation of stem cell properties, lineage-specific differentiation, and niche interaction. α6-Integrin subunit can be alternatively spliced at the post-transcriptional level, giving rise to divergent isoforms which differ in the cytoplasmic and/or extracellular domains. The cytoplasmic domain of integrins is an important functional part of integrin-mediated signals. Structural changes in the cytoplasmic domain of α6 provide an efficient means for the regulation of stem cell responses to biochemical stimuli and/or biophysical cues in the stem cell niche, thus impacting stem cell fate determination. In this review, we summarize the current knowledge on the structural variants of the α6-integrin subunit and spatiotemporal expression of α6 cytoplasmic variants in embryonic and adult stem/progenitor cells. We highlight the roles of α6 cytoplasmic variants in stem cell fate decision and niche interaction, and discuss the potential mechanisms involved. Understanding of the distinct functions of α6 splicing variants in stem cell biology may inform the rational design of novel stem cell-based therapies for a range of human diseases.
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http://dx.doi.org/10.1186/s13287-018-0868-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930856PMC
May 2018

Prevalence and characteristics of COPD among pneumoconiosis patients at an occupational disease prevention institute: a cross-sectional study.

BMC Pulm Med 2018 Jan 29;18(1):22. Epub 2018 Jan 29.

Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Background: Pneumoconiosis may play an important role in the development of chronic obstructive pulmonary disease (COPD), and the complication of COPD may impose a heavy burden of illness.

Methods: The study was conducted in Hunan Province in China from December 1, 2015, to December 1, 2016. Consecutive underground male pneumoconiosis patients employed for at least 1 year were recruited from the Hunan Occupational Disease Prevention Institute. Patient information, respiratory symptoms and clinical data were collected using a structured questionnaire. The diagnosis of COPD were assessed using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Logistic regression analyses were conducted to examine the clinical and demographic risk factors of COPD among pneumoconiosis patients.

Results: The prevalence of COPD in our sample of pneumoconiosis patients was 18.65% (119/638). In pneumoconiosis patients with and without smoking history, the prevalence of COPD was 19.32 and 16.77%. Compared with non-COPD patients, those with COPD are older in age, have longer exposure time, have lower body mass index (BMI), have a higher smoking index and have worse pulmonary function (all p < 0.05). For the five respiratory symptoms (cough, sputum, wheeze, dyspnea, and chest tightness), only the presence of wheeze and the severity scores for wheeze or dyspnea showed significant differences between the COPD and non-COPD groups (p < 0.01). Multivariate logistic regression analysis revealed that advanced pneumoconiosis category, older age and the presence of wheeze symptoms were significant risk factors for the development of COPD among pneumoconiosis patients.

Conclusion: Pneumoconiosis patients are at a high risk of COPD, and pneumoconiosis patients with COPD may suffer more severe respiratory symptoms, such as wheeze and dyspnea, than patients without COPD. Advanced pneumoconiosis category, older age and the presence of wheeze symptoms are associated with an increased risk of COPD in pneumoconiosis. We proposed that a routine assessment of lung function is necessary for timely and adequate clinical management.
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http://dx.doi.org/10.1186/s12890-018-0581-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789671PMC
January 2018

The recent advances of phenotypes in acute exacerbations of COPD.

Int J Chron Obstruct Pulmon Dis 2017 27;12:1009-1018. Epub 2017 Mar 27.

Department of Respiratory Medicine, The Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, People's Republic of China.

Exacerbations of COPD are clinically relevant events with therapeutic and prognostic implications. Yet, significant heterogeneity of clinical presentation and disease progression exists within acute exacerbations of COPD (AECOPD). Currently, different phenotypes have been widely used to describe the characteristics among patients with AECOPD. This has proved to be significant in the treatment and prediction of the outcomes of the disease. In this review of published literature, the phenotypes of AECOPD were classified according to etiology, inflammatory biomarkers, clinical manifestation, comorbidity, the frequency of exacerbations, and so on. This review concentrates on advancements in the use of phenotypes of AECOPD.
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http://dx.doi.org/10.2147/COPD.S128604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375638PMC
October 2017

Evaluating the Clinical COPD Questionnaire: A systematic review.

Respirology 2017 02;22(2):251-262

Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

The Clinical COPD Questionnaire (CCQ) is recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) to evaluate health status in patients with COPD. The objective of this work was to systemically assess the reliability, validity, responsiveness and minimum clinically important difference (MCID) of the CCQ. A structured search was conducted in three databases to identify articles that evaluated the psychometric properties of the CCQ in individuals with COPD. Two investigators screened the title, abstract and full text of the articles to determine study eligibility and performed the data extraction. Quality assessment of included studies was assessed by the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) checklist. Finally, 43 studies were included, over half of which had fair methodological quality. Internal consistency (reliability) of the CCQ total score ranged from 0.84 to 0.94, and test-retest reliability was 0.70-0.99. The overall CCQ had a better correlation with St George's Respiratory Questionnaire (SGRQ; from 0.71 to 0.88) and COPD Assessment Test (CAT; from 0.64 to 0.88) than modified Medical Research Council (mMRC; from 0.392 to 0.668) and forced expiratory volume in 1 s (FEV % predicted; from -0.31 to -0.68). Scores were different within GOLD stages, groups, composite events and co-morbidities. CCQ was sensitive to exacerbations, pulmonary rehabilitation and smoking cessation with the MCID of 0.4. The CCQ is a very useful and practical tool that can be used in clinical populations with good reliability, validity and responsiveness to interventions.
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http://dx.doi.org/10.1111/resp.12970DOI Listing
February 2017

Are healthy smokers really healthy?

Tob Induc Dis 2016 15;14:35. Epub 2016 Nov 15.

Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011 People's Republic of China.

Cigarette smoke contains more than 4500 chemicals which have toxic, mutagenic and carcinogenic effects. Strong evidences have shown that current smokers take a significantly higher risk of cardiovascular diseases, chronic obstructive pulmonary disease (COPD) and lung cancer than nonsmokers. However, less attention has been paid to the smoking induced abnormalities in the individuals defined as healthy smokers who are normal with spirometry, radiographic images, routine physical exam and categorized as healthy control group in many researches. Actually, 'healthy smokers' are not healthy. This narrative review focuses on the smoking related pathophysiologic changes mainly in the respiratory system of healthy smokers, including inflammation and immune changes, genetic alterations, structural changes and pulmonary dysfunction.
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http://dx.doi.org/10.1186/s12971-016-0101-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111288PMC
November 2016

Detection of pulmonary arteriovenous fistula with three-dimensional computed tomographic angiography.

Eur Heart J 2016 11 18;37(42):3210. Epub 2016 Feb 18.

Department of the Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China

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http://dx.doi.org/10.1093/eurheartj/ehv763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181383PMC
November 2016

Development of a novel-type transgenic cotton plant for control of cotton bollworm.

Plant Biotechnol J 2016 08 3;14(8):1747-55. Epub 2016 Feb 3.

College of Agriculture and Biotechnology, China Agricultural University, Beijing, China.

The transgenic Bt cotton plant has been widely planted throughout the world for the control of cotton budworm Helicoverpa armigera (Hubner). However, a shift towards insect tolerance of Bt cotton is now apparent. In this study, the gene encoding neuropeptide F (NPF) was cloned from cotton budworm H. armigera, an important agricultural pest. The npf gene produces two splicing mRNA variants-npf1 and npf2 (with a 120-bp segment inserted into the npf1 sequence). These are predicted to form the mature NPF1 and NPF2 peptides, and they were found to regulate feeding behaviour. Knock down of larval npf with dsNPF in vitro resulted in decreases of food consumption and body weight, and dsNPF also caused a decrease of glycogen and an increase of trehalose. Moreover, we produced transgenic tobacco plants transiently expressing dsNPF and transgenic cotton plants with stably expressed dsNPF. Results showed that H. armigera larvae fed on these transgenic plants or leaves had lower food consumption, body size and body weight compared to controls. These results indicate that NPF is important in the control of feeding of H. armigera and valuable for production of potential transgenic cotton.
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http://dx.doi.org/10.1111/pbi.12534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067616PMC
August 2016

Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia.

FASEB J 2016 Apr 18;30(4):1579-89. Epub 2015 Dec 18.

*Division of Life Science, Division of Biomedical Engineering, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial ligand-gated anion channel, are associated with the lethal genetic disease cystic fibrosis. The CFTR G551D mutation impairs ATP hydrolysis and thereby makes CFTR refractory to cAMP stimulation. Both wild-type (WT) and G551D CFTR have been implicated in regulatory volume decrease (RVD), but the underlying mechanism remains incompletely understood. Here, we show that the channel activity of both WT and G551D CFTR is directly stimulated by mechanical perturbation induced by cell swelling at the single-channel, cellular, and tissue levels. Hypotonicity activated CFTR single channels in cell-attached membrane patches and WT-CFTR-mediated short-circuit current (Isc) in Calu-3 cells, and this was independent of Ca(2+)and cAMP/PKA signaling. Genetic suppression and ablation but not G551D mutation of CFTR suppressed the hypotonicity- and stretch-inducedIscin Calu-3 cells and mouse duodena. Moreover, ablation but not G551D mutation of the CFTR gene inhibited the RVD of crypts isolated from mouse intestine; more importantly, CFTR-specific blockers markedly suppressed RVD in both WT- and G551D CFTR mice, demonstrating for the first time that the channel activity of both WT and G551D CFTR is required for epithelial RVD. Our findings uncover a previously unrecognized mechanism underlying CFTR involvement in epithelial RVD and suggest that the mechanosensitivity of G551D CFTR might underlie the mild phenotypes resulting from this mutation.-Xie, C., Cao, X., Chen, X, Wang, D., Zhang, W. K., Sun, Y., Hu, W., Zhou, Z., Wang, Y., Huang, P. Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia.
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http://dx.doi.org/10.1096/fj.15-283002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137689PMC
April 2016

Progress and challenges in generating functional hematopoietic stem/progenitor cells from human pluripotent stem cells.

Cytotherapy 2015 Apr 10;17(4):344-58. Epub 2015 Feb 10.

Bone Marrow Transplantation Centre, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. Electronic address:

The generation of hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) in vitro holds great potential for providing alternative sources of donor cells for clinical HSC transplantation. However, the low efficiency of current protocols for generating blood lineages and the dysfunction identified in hPSC-derived hematopoietic cells limit their use for full hematopoietic reconstitution in clinics. This review outlines the current understanding of in vitro hematopoietic differentiation from hPSCs, emphasizes the intrinsic and extrinsic molecular mechanisms that are attributed to the aberrant phenotype and function in hPSC-derived hematopoietic cells, pinpoints the current challenges to develop the truly functional HSCs from hPSCs for clinical applications and explores their potential solutions.
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http://dx.doi.org/10.1016/j.jcyt.2015.01.003DOI Listing
April 2015

Efficacy of Heparinoid PSS in Treating Cardiovascular Diseases and Beyond-A Review of 27 Years Clinical Experiences in China.

Clin Appl Thromb Hemost 2016 Apr 25;22(3):222-9. Epub 2014 Sep 25.

School of Medicine and Pharmacy, Ocean University of China, Qingdao, China

Propylene glycol alginate sodium sulfate (PSS) is the world's first oral heparinoid approved by Chinese Food and Drug Administration in 1987. Propylene glycol alginate sodium sulfate is produced by modifying partially hydrolyzed alginate, one of the most abundant marine polysaccharides isolated from brown algae, by epoxypropane esterification and by chemical sulfation. It is used for treating and preventing cardiovascular-related diseases. The low cost (US$1.29/100 tablets, ∼4 tablets/day), remarkable clinical effects, and convenient oral administration make PSS an ideal long-term prevention drug. Propylene glycol alginate sodium sulfate is available in most drug stores in China, and millions of patients take PSS routinely during the past 27 years. The 22 784 reported clinical cases as well as the structure, preparation, clinical efficacy, adverse reactions, pharmacokinetics, pharmacodynamics, and future perspectives of PSS based on the results of peer-reviewed publications will be discussed. This review should bring the knowledge of PSS gained in China to the world to stimulate in depth academic and clinical studies of PSS.
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http://dx.doi.org/10.1177/1076029614551822DOI Listing
April 2016

Salinity-induced anti-angiogenesis activities and structural changes of the polysaccharides from cultured Cordyceps Militaris.

PLoS One 2014 9;9(9):e103880. Epub 2014 Sep 9.

Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience & Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.

Cordyceps is a rare and exotic mushroom that grows out of the head of a mummified caterpillar. Many companies are cultivating Cordyceps to meet the increased demand for its medicinal applications. However, the structures and functions of polysaccharides, one of the pharmaceutical active ingredients in Cordyceps, are difficult to reproduce in vitro. We hypothesized that mimicking the salty environment inside caterpillar bodies might make the cultured fungus synthesize polysaccharides with similar structures and functions to that of wild Cordyceps. By adding either sodium sulfate or sodium chloride into growth media, we observed the salinity-induced anti-angiogenesis activities of the polysaccharides purified from the cultured C. Militaris. To correlate the activities with the polysaccharide structures, we performed the (13)C-NMR analysis and observed profound structural changes including different proportions of α and β glycosidic bonds and appearances of uronic acid signals in the polysaccharides purified from the culture after the salts were added. By coupling the techniques of stable (34)S-sulfate isotope labeling, aniline- and D5-aniline tagging, and stable isotope facilitated uronic acid-reduction with LC-MS analysis, our data revealed for the first time the existence of covalently linked sulfate and the presence of polygalacuronic acids in the polysaccharides purified from the salt added C. Militaris culture. Our data showed that culturing C. Militaris with added salts changed the biosynthetic scheme and resulted in novel polysaccharide structures and functions. These findings might be insightful in terms of how to make C. Militaris cultures to reach or to exceed the potency of wild Cordyceps in future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103880PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159134PMC
May 2015