Publications by authors named "Chunlan Yang"

43 Publications

A 4-day-old newborn with an isolated sternal cleft: A rare case and literature review.

Pediatr Pulmonol 2021 Oct 12. Epub 2021 Oct 12.

Department of Medical Imaging, Guangdong Second Provincial General Hospital, Guangzhou, China.

An isolated sternal cleft is an orphan congenital defect of the sternum that presents from birth to adulthood. We report the case of a 4-day-old newborn with an isolated congenital cleft sternum. We also reviewed the related literature and operative options.
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http://dx.doi.org/10.1002/ppul.25677DOI Listing
October 2021

[Clinical and genetic analysis of a child with transcobalamin II deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Oct;38(10):993-996

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518000, China.

Objective: To investigate the genetic etiology, clinical diagnosis and treatment of a child with pancytopenia, failure to thrive and pulmonary infection.

Methods: Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted. Genetic variants associated with hematological diseases were detected by high-throughput sequencing.

Results: Three variants of TCN2 gene were found, one of which located in exon 5 upstream(c.581-8A>T), the parents has carried this variant; one in exon 6 (c.924_927del), the variant was originated from the mother; one in exon 7 (c.973C>T), the variant has ocurred de novo. The variants pathogenic analysis combined with clinical manifestation, pancytopenia, the increase in methylmalonic acid level and increased homocysteine, the child was diagnosed with transcobalaminIIdeficiency. The patient presented with respiratory infection, which was confirmed to be pneumocystosis by lung radioscopy and pathogenic high-throughput sequencing of broncho-alveolar lavage fluid. The patient presented with acute respiratory distress syndrome during the treatment with intramuscular injection of vitamin B, and improved after anti-infection with compound sulfamethoxazole and symptomatic support treatment.

Conclusion: We reported a case of Chinese child with TCNII deficiency due to novel gene variant, and analyzed the pathogenicity of the three variants. The treatment of TCNII deficiency with cobalamin should be individualized.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200408-00247DOI Listing
October 2021

Individual-level morphological hippocampal networks in patients with Alzheimer's disease.

Brain Cogn 2021 07 7;151:105748. Epub 2021 May 7.

Department of Radiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong 264000, China. Electronic address:

In patients with Alzheimer's Disease (AD), the hippocampal network has been extensively investigated in previous studies; however, little is known about the morphological network associated with the hippocampus in the AD patients. A total of 68 patients with AD and another 68 gender and age matched healthy subjects were studied. Individual-level morphological hippocampal networks were constructed based on volume and texture features extracted from MRI to study the connections between bilateral hippocampus and 11 other subcortical gray matter structures. The relationship between morphological connections and Mini-Mental State Examination (MMSE) scores was also studied. Connections between bilateral hippocampus and bilateral thalamus, bilateral putamen were significant differences between the AD patients and controls (p < 0.05). There were significantly different in bilateral hippocampal connectivity, and for the left hippocampus, the connection to the right caudate were found to be statistically significant. The morphological connections between left hippocampus and bilateral thalamus (left: R = 0.371, p < 0.001; right: R = 0.411, p < 0.001), bilateral putamen (left: R = 0.383, p < 0.001; right: R = 0.348, p < 0.001), right hippocampus and bilateral thalamus (left: R = 0.370, p < 0.001; right: R = 0.387, p < 0.001), left putamen (R = 0.377, p < 0.001) were significantly positively correlated with the MMSE scores. Similar patterns were observed for left and right hippocampal connectivity and the connections highly associated with MMSE scores were also within the abnormal connections in AD patients.
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http://dx.doi.org/10.1016/j.bandc.2021.105748DOI Listing
July 2021

Cytomegalovirus Infection and the Implications of Drug-Resistant Mutations in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Retrospective Study from a Tertiary Hospital in China.

Infect Dis Ther 2021 Sep 8;10(3):1309-1322. Epub 2021 May 8.

Department of Hematology and Oncology, Shenzhen Children's Hospital, Yitian Road No. 7019, Futian, Shenzhen, 518038, China.

Introduction: Drug-resistant cytomegalovirus (CMV) infection remains a challenge in the management of pediatric recipients of hematopoietic stem cell transplantation (HSCT). In this study, we retrospectively reviewed the clinical data on pediatric recipients of HSCT and identified known and unknown drug-resistant CMV variants.

Methods: A total of 221 children underwent allogeneic HSCT between October 2017 and November 2019 at Shenzhen Children's Hospital; of these, 35 patients were suspected of having drug-resistant CMV infections and were tested for drug-resistant mutations in the UL97 and UL54 genes by Sanger sequencing.

Results: Mutations in UL97 or UL54, or in both, were detected in 11 patients. Most of these mutations have not been previously reported. The UL97 mutation (A582V) was detected in only one patient who also harbored two UL54 mutations (T760X and R876W). One patient with both the G604S and T691A mutations in the UL54 gene died of CMV pneumonia. We investigated the risk factors associated with the development of drug-resistant CMV infection. Patients in whom both the donor and recipient had positive CMV serostatuses were less likely to have drug-resistant mutations (Fisher's exact test, p < 0.05).

Conclusion: Newly and previously detected CMV mutations in UL97 and UL54 may be associated with the development of drug-resistant CMV infection. The detection of these mutations may provide guidance for the management of post-transplant CMV infections.
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http://dx.doi.org/10.1007/s40121-021-00452-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322184PMC
September 2021

Co-Transplantation of Haploidentical Stem Cells and a Dose of Unrelated Cord Blood in Pediatric Patients with Thalassemia Major.

Cell Transplant 2021 Jan-Dec;30:963689721994808

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.

Allogeneic stem cell transplantation is a cure for patients suffering from thalassemia major (TM). Historically, patients were limited by the selection of donors, while the advancement of haploidentical stem cell transplantation (haplo-SCT) has greatly expanded the donor pool. However, the outcomes of haplo-SCT in TM recipients vary between different programs. In this study, we retrospectively studied 73 pediatric TM patients (median age, 7 years; range, 3 to 14 years) who underwent haplo-cord transplantation. Both the estimated overall survival and transfusion-free survival were 95.26% (CI 95.77% to 96.23%). Neither primary nor secondary graft failures were observed. The median follow-up period was 811 days (range, 370 to 1433 days). Median neutrophil and platelet engraftment times were 22 days (range, 8 to 48 days) and 20 days (range, 8 to 99 days), respectively. Acute graft-versus-host disease (aGVHD) was observed in 52% of patients and of these, 25% developed grade III to IV aGVHD. Cord blood engraftment was associated with delayed immune recovery and increased aGVHD severity. Viral DNAemia occurred in a relatively high proportion of patients but only 7% of patients developed CMV disease, while another 7% of patients had post-transplantation lymphoproliferative disorder. Long-term complication outcomes were good. Only one patient developed extensive chronic GVHD. No surviving patients were reliant on blood transfusion by the time this manuscript was submitted. This is one of the largest studies on the outcomes of pediatric TM patients who received stem cell transplantations from alternative donors. The haplo-cord program is safe and practical for TM patients that do not have matched donors.
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http://dx.doi.org/10.1177/0963689721994808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894585PMC
February 2021

Identification and Treatment of Tuberculosis in Pediatric Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Review of the Literature.

Infect Drug Resist 2020 31;13:2641-2648. Epub 2020 Jul 31.

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, People's Republic of China.

Background: Tuberculosis is a rare but life-threatening complication in patients who received hematopoietic stem cell transplantation. Early identification and intervention are essential to prevent severe complications.

Case Presentation: We report two pediatric patients who developed tuberculosis after receiving hematopoietic stem cell transplantation for thalassemia major among 330 recipients between January 2012 and August 2019. Patient A presented with pulmonary tuberculosis and patient B presented with lymph node tuberculosis mimicking post-transplantation lymphoproliferative disorder associated with Epstein-Barr virus reactivation. Patient B's condition was deteriorated, and shortly after the initiation of anti-tuberculosis therapy, the patient was found to have disseminated pulmonary tuberculosis. Patient B was also found to have tuberculous granulomas, an uncommon manifestation of tuberculosis causing severe airway obstruction. Both patients developed critical respiratory failure and required mechanical ventilation; however, they recovered with almost full resolution of pulmonary lesions after multiple treatment adjustments.

Conclusion: Tuberculosis must be carefully evaluated in all pediatric patients that receive hematopoietic stem cell transplantation, regardless of the identification of other pathogens. Prophylactic tuberculosis therapy should be considered for high-risk pediatric hematopoietic stem cell transplantation recipients from tuberculosis-endemic regions.
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http://dx.doi.org/10.2147/IDR.S256298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406069PMC
July 2020

White Matter Structural Brain Connectivity of Young Healthy Individuals With High Trait Anxiety.

Front Neurol 2019 13;10:1421. Epub 2020 Feb 13.

Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Although functional brain connectivity in anxiety-related disorders has been studied, brain connectivity in non-clinical populations with high trait anxiety has been rarely reported. Whether structural brain connectivity changes in young healthy individuals with high trait anxiety remains unknown. Thirty-eight young healthy individuals with high anxiety levels and 34 healthy subjects with low anxiety levels who were matched by age, gender, and educational level were recruited. Diffusion tensor images were acquired to analyze white matter connectivity. A two-sample -test was used for group comparison of weighted networks and graph properties. Different connections were detected in fractional anisotropy- and fiber number-weighted networks. These connections were widely distributed in various regions, where relative significance was located in the inter-hemispheric frontal lobe, the frontal-limbic lobe in the right intra-hemisphere, and the frontal-temporal lobe in the ipsilateral hemisphere. However, no significant difference was found in fiber length-weighted network and in graph properties among the three networks. The structural connectivity of white matter may be a vulnerability marker. Hence, healthy individuals with high trait anxiety levels are susceptible to anxiety-related psychopathology. The findings may help elucidate the pathological mechanism of anxiety and establish interventions for populations susceptible to anxiety disorders.
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http://dx.doi.org/10.3389/fneur.2019.01421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031248PMC
February 2020

Inhibitory mechanism of muscone in liver cancer involves the induction of apoptosis and autophagy.

Oncol Rep 2020 Mar 29;43(3):839-850. Epub 2020 Jan 29.

Key Laboratory of Bio‑Resource and Eco‑Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610065, P.R. China.

Traditionally, musk has been used as an analgesic to treat pain associated with cancer. Hepatocellular carcinoma (HCC) is an aggressive tumor; however, patients with liver cancer that received musk were reported to live longer and have a higher quality of life. Thus, the present study aimed to investigate whether muscone, a macrocyclic compound of musk, demonstrated potential as an anti‑liver cancer drug for the non‑surgical treatment of advanced liver cancer. Briefly, liver cancer cells were treated with muscone and the rates of cellular apoptosis and autophagy were investigated using staining techniques and western blotting. The underlying molecular mechanisms of muscone were evaluated using high‑throughput sequencing and the in vitro effects of muscone were subsequently validated in vivo using a nude mouse model. Muscone increased the rates of apoptosis and autophagy in liver cancer cells; the increase in cellular apoptosis was observed to occur through endoplasmic reticulum stress responses, whereas muscone‑induced autophagy was closely associated with the AMP kinase/mTOR complex 1 signaling pathway. These findings were verified in vivo. Notably, sestrin‑2 expression levels were also significantly decreased in liver cancer tissues compared with paracancerous tissues. In conclusion, the present study suggests that muscone demonstrates potential as an anticancer drug, and the findings of the present study provide the basis for the development of effective anticancer drugs derived from natural compounds.
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http://dx.doi.org/10.3892/or.2020.7484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041171PMC
March 2020

EasyMEG: An easy-to-use toolbox for MEG analysis.

Comput Methods Programs Biomed 2020 Apr 12;186:105199. Epub 2019 Nov 12.

Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.

Background And Objective: Magnetoencephalography (MEG) is an advanced magnetic source imaging technology that measures the magnetic fields produced by neural activities. It has been extensively used in scientific research and clinical diagnosis due to its high temporal and spatial resolution. Considering the special nature of MEG data, it needs to perform a series of processes and analysis to obtain valuable information. Therefore, the identification of data processing is a key point of MEG studies. At present, the software for MEG analysis such as FieldTrip has no Graphic User Interface (GUI) and users must write their own script to perform concrete analysis. It brings the difficulties to researchers like the doctors without experience in programming or newcomers to MEG. Thus, an open-sourced software-EasyMEG was developed. It has friendly interface with highly functions-integration.

Methods: The functions of EasyMEG are developed based on MATLAB language to ensure the consistency of the user interface under different operating systems. EasyMEG is a highly integrated software that contains a set of functions for preprocessing, time-lock analysis, time-frequency analysis, source analysis, and plotting. EasyMEG provides a friendly GUI and allows users to complete analyses through a simple and clean interface.

Results: This toolbox has been released as an open-source software on GitHub under the GNU General Public License: https://tonywu2018.github.io/EasyMEG/.

Conclusions: We hope to improve this toolbox by the power of community and wish to make EasyMEG a simple and powerful toolbox for further MEG studies.
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http://dx.doi.org/10.1016/j.cmpb.2019.105199DOI Listing
April 2020

In vitro anticancer effects of esculetin against human leukemia cell lines involves apoptotic cell death, autophagy, G0/G1 cell cycle arrest and modulation of Raf/MEK/ERK signalling pathway.

J BUON 2019 Jul-Aug;24(4):1686-1691

Department of Hematology and Oncology, Shenzhen Children's Hospital, No.7019 Yitian Rd, Shenzhen, Guangdong, 518038, China.

Purpose: Esculetin is an important bioactive coumarin with amazing potential to suppress the growth of cancer cells. The present study was designed to investigate the anticancer effects of esculetin against the human leukemia HL-60 cells.

Methods: CCK-8 assay was used to assess cell viability. DAPI and annexin V/propidium iodide (PI) staining was performed to investigate the induction of apoptosis. Autophagy was detected by electron microscopic analysis. Flow cytometry was used for cell cycle analysis and Western blotting was used to estimate protein expression.

Results: Esculetin suppressed the proliferation of HL-60 cells dose-dependently. The IC50 of esculetin against HL-60 cells was observed to be 20 µM. The anticancer effects of esculetin against HL-60 cells occurred though different mechanisms. Esculetin induced apoptosis and autophagy in leukemia cells, which were accompanied by alteration in the expression of apoptosis as well as autophagy-related proteins. Esculetin also triggered G0/G1 cell cycle arrest in HL-60 cells, which was also accompanied by suppression of Cyclin D1 and D3. Esculetin could also block the Raf/MEK/ERK signalling pathway in leukemia cells in a concentration-dependent manner.

Conclusion: These results indicate that esculetin inhibits the growth of leukemia cells and hence may prove beneficial for treating leukemia.
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March 2020

Altered Functional Connectivity in Children With Low-Function Autism Spectrum Disorders.

Front Neurosci 2019 2;13:806. Epub 2019 Aug 2.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Neuroimaging studies have shown that autism spectrum disorders (ASDs) may be associated with abnormalities in brain structures and functions at rest as well as during cognitive tasks. However, it remains unclear if functional connectivity (FC) of all brain neural networks is also changed in these subjects. In this study, we acquired functional magnetic resonance imaging scans from 93 children with ASD and 79 matched healthy subjects. Group independent component analysis was executed for all of the participants to estimate FC. One-sample -tests were then performed to obtain the networks for each group. Group differences in the different brain networks were tested using two-sample -tests. Finally, relationships between abnormal FC and clinical variables were investigated with Pearson's correlation analysis. The results from one-sample -tests revealed nine networks with similar spatial patterns in these two groups. When compared with the controls, children with ASD showed increased connectivity in the right dorsolateral superior frontal gyrus and left middle frontal gyrus (MFG) within the occipital pole network. Children with ASD also showed decreased connectivity in the left gyrus rectus, left middle occipital gyrus, right angular gyrus, right MFG and right inferior frontal gyrus (IFG), orbital part within the lateral visual network (LVN), the left IFG, right precuneus, and right angular gyrus within the left frontoparietal (cognition) network. Furthermore, the mean FC values within the LVN showed significant positive correlations with total score of the Childhood Autism Rating Scale. Our findings indicate that abnormal FC extensively exists within some networks in children with ASD. This abnormal FC may constitute a biomarker of ASD. Our results are an important contribution to the study of neuropathophysiological mechanisms in children with ASD.
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http://dx.doi.org/10.3389/fnins.2019.00806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688725PMC
August 2019

[A new method for classification of Alzheimer's disease combined with structural magnetic resonance imaging texture features].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2019 Feb;36(1):94-100

College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, P.R.China.

In this paper, a new method for the classification of Alzheimer's disease (AD) using multi-feature combination of structural magnetic resonance imaging is proposed. Firstly, hippocampal segmentation and cortical thickness and volume measurement were performed using FreeSurfer software. Then, histogram, gradient, length of gray level co-occurrence matrix and run-length matrix were used to extract the three-dimensional (3D) texture features of the hippocampus, and the parameters with significant differences between AD, MCI and NC groups were selected for correlation study with MMSE score. Finally, AD, MCI and NC are classified and identified by the extreme learning machine. The results show that texture features can provide better classification results than volume features on both left and right sides. The feature parameters with complementary texture, volume and cortical thickness had higher classification recognition rate, and the classification accuracy of the right side (100%) was higher than that of the left side (91.667%). The results showed that 3D texture analysis could reflect the pathological changes of hippocampal structures of AD and MCI patients, and combined with multi-feature analysis, it could better reflect the essential differences between AD and MCI cognitive impairment, which was more conducive to clinical differential diagnosis.
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http://dx.doi.org/10.7507/1001-5515.201803039DOI Listing
February 2019

Alterations of Graphic Properties and Related Cognitive Functioning Changes in Mild Alzheimer's Disease Revealed by Individual Morphological Brain Network.

Front Neurosci 2018 10;12:927. Epub 2018 Dec 10.

Department of Biomedical Sciences, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.

Alzheimer's disease (AD) is one of the most common forms of dementia that has slowly negative impacts on memory and cognition. With the assistance of multimodal brain networks and graph-based analysis approaches, AD-related network disruptions support the hypothesis that AD can be identified as a dysconnectivity syndrome. However, as the recent emerging of individual-based morphological network research of AD, the utilization of multiple morphometric features may provide a broader horizon for locating the lesions. Therefore, the present study applied the newly proposed individual morphological brain network with five commonly used morphometric features (cortical thickness, regional volume, surface area, mean curvature, and fold index) to explore the topological aberrations and their relationship with cognitive functioning alterations in the early stage of AD. A total of 40 right-handed participants were selected from Open Access Series of Imaging Studies Database with 20 AD patients (age ranged from 70 to 79, CDR = 0.5) and 20 age/gender-matched healthy controls. The significantly affected connections ( < 0.05 with FDR correction) were observed across multiple regions, both enhanced and attenuated correlations, primarily related to the left entorhinal cortex (ENT). In addition, profoundly changed Mini Mental State Examination (MMSE) score and global efficiency ( < 0.05) were noted in the AD patients, as well as the pronounced inter-group distinctions of betweenness centrality, global and local efficiency ( < 0.05) in the higher MMSE score zone (28-30), which indicating the potential role of graphic properties in determination of early-stage AD patients. Moreover, the reservations (regions in the occipital and frontal lobes) and alterations (regions in the right temporal lobe and cingulate cortex) of hubs were also detected in the AD patients. Overall, the findings further confirm the selective AD-related disruptions in morphological brain networks and also suggest the feasibility of applying the morphological graphic properties in the discrimination of early-stage AD patients.
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http://dx.doi.org/10.3389/fnins.2018.00927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295573PMC
December 2018

An efficient optic cup segmentation method decreasing the influences of blood vessels.

Biomed Eng Online 2018 Sep 26;17(1):130. Epub 2018 Sep 26.

Department of Ophthalmology, Hospital of Beijing University of Technology, Beijing, 100124, China.

Background: Optic cup is an important structure in ophthalmologic diagnosis such as glaucoma. Automatic optic cup segmentation is also a key issue in computer aided diagnosis based on digital fundus image. However, current methods didn't effectively solve the problem of edge blurring caused by blood vessels around the optic cup.

Methods: In this study, an improved Bertalmio-Sapiro-Caselles-Ballester (BSCB) model was proposed to eliminate the noising induced by blood vessel. First, morphological operations were performed to get the enhanced green channel image. Then blood vessels were extracted and filled by improved BSCB model. Finally, Local Chart-Vest model was used to segment the optic cup. A total of 94 samples which included 32 glaucoma fundus images and 62 normal fundus images were experimented.

Results: The evaluation parameters of F-score and the boundary distance achieved by the proposed method against the results from experts were 0.7955 ± 0.0724 and 11.42 ± 3.61, respectively. Average vertical optic cup-to-disc ratio values of the normal and glaucoma samples achieved by the proposed method were 0.4369 ± 0.1193 and 0.7156 ± 0.0698, which were also close to those by experts. In addition, 39 glaucoma images from the public dataset RIM-ONE were also used for methodology evaluation.

Conclusions: The results showed that our proposed method could overcome the influence of blood vessels in some degree and was competitive to other current optic cup segmentation algorithms. This novel methodology will be expected to use in clinic in the field of glaucoma early detection.
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http://dx.doi.org/10.1186/s12938-018-0560-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158914PMC
September 2018

Cerebral White Matter Changes in Young Healthy Individuals With High Trait Anxiety: A Tract-Based Spatial Statistics Study.

Front Neurol 2018 24;9:704. Epub 2018 Aug 24.

College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.

Abnormalities in prespecified and empirical white matter tracts in young patients with anxiety-related disorders have been reported in some diffusion tensor imaging (DTI) studies. However, with few literatures examining the association between the integrity of whole brain white matter and trait anxiety levels in the non-clinical populations, whether white matter changes arise in young healthy individuals with high trait anxiety remains unknown. We examined whole brain white matter alterations in young healthy individuals with high anxiety but without history of neurological or psychiatric disorders via DTI technology. Group comparison of tract-based spatial statistics (TBSS) was performed to investigate the microstructural diffusion alterations in 38 high anxious subjects in comparison with 34 low anxious subjects matched with age, gender, and degree of education. These analyses controlled for depression to establish specificity to trait anxiety. Young healthy subjects with high trait anxiety had significantly decreased fractional anisotropy (FA) values in multiple clusters, including corona radiate (CR), anterior thalamic radiation (ATR), inferior fronto-occipital fasciculus (IFOF), bilaterally, body, genu, and splenium of corpus callosum (CC) and forceps minor, compared with low trait anxious subjects. For the abnormal FA regions, the other diffusion metrics were also altered slightly. Non-clinical individuals with high anxiety already have white matter alterations in the thalamus-cortical circuit and some emotion-related areas that were widely reported in anxiety-related disorders. The altered white matter may be a vulnerability marker in individuals at high risk of clinical anxiety. These findings can deepen our understanding of the pathological mechanism of anxiety and further support the need for preventive interventions in high anxiety individuals.
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http://dx.doi.org/10.3389/fneur.2018.00704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117387PMC
August 2018

Computer-aided identification of a novel pyruvate kinase M2 activator compound.

Cell Prolif 2018 Dec 21;51(6):e12509. Epub 2018 Aug 21.

College of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.

Objectives: The aim of this study was to obtain antitumour molecules targeting to activate PKM2 through adequate computational methods combined with biological activity experiments.

Methods: The structure-based virtual screening was utilized to screen effective activator targeting PKM2 from ZINC database. Molecular dynamics simulations were performed to evaluate the stability of the small molecule-binding PKM2 complex systems. Then, cell survival experiments, glutaraldehyde crosslinking reaction, western blot, and qPCR experiments were used to detect the effects of top hits on various cancer cells and the targeting specificity of PKM2.

Results: Two small molecules in 1,5-2H-pyrrole-dione were obtained after virtual screening. In vitro experiments demonstrated that ZINC08383544 specifically activated PKM2 and affected the expression of upstream and downstream genes of PKM2 during glycolysis, leading to the inhibition of tumour cell growth. These results indicate that ZINC08383544 conforms to the characteristics of PKM2 activator and is potential to be a novel PKM2 activator as antitumour drug.

Discussion: This work proves that ZINC08383544 promotes the formation of PKM2 tetramer, effectively blocks PKM2 nuclear translocation, and inhibits the growth of tumour, and ZINC08383544 may be a novel activator of PKM2. This work may provide a good choice of drug or molecular fragments for the antitumour strategy targeting PKM2. Screening of targeted drugs by combination of virtual screening and bioactivity experiments is a rapid method for drug discovery.
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http://dx.doi.org/10.1111/cpr.12509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528871PMC
December 2018

Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

Brain Topogr 2018 07 16;31(4):577-590. Epub 2018 Apr 16.

College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.

Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.
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http://dx.doi.org/10.1007/s10548-018-0642-yDOI Listing
July 2018

Age-Related Gray and White Matter Changes in Normal Adult Brains.

Aging Dis 2017 Dec 1;8(6):899-909. Epub 2017 Dec 1.

1College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100022, China.

Normal aging is associated with both structural changes in many brain regions and functional declines in several cognitive domains with advancing age. Advanced neuroimaging techniques enable explorative analyses of structural alterations that can be used as assessments of such age-related changes. Here we used voxel-based morphometry (VBM) to investigate regional and global brain volume differences among four groups of healthy adults from the IXI Dataset: older females (OF, mean age 68.35 yrs; n=69), older males (OM, 68.43 yrs; n=66), young females (YF, 27.09 yrs; n=71), and young males (YM, 27.91 yrs; n=71), using 3D T1-weighted MRI data. At the global level, we investigated the influence of age and gender on brain volumes using a two-way analysis of variance. With respect to gender, we used the Pearson correlation to investigate global brain volume alterations due to age in the older and young groups. At the regional level, we used a flexible factorial statistical test to compare the means of gray matter (GM) and white matter (WM) volume alterations among the four groups. We observed different patterns in both the global and regional GM and WM alterations in the young and older groups with respect to gender. At the global level, we observed significant influences of age and gender on global brain volumes. At the regional level, the older subjects showed a widespread reduction in GM volume in regions of the frontal, insular, and cingulate cortices compared to the young subjects in both genders. Compared to the young subjects, the older subjects showed a widespread WM decline prominently in the thalamic radiations, in addition to increased WM in pericentral and occipital areas. Knowledge of these observed brain volume differences and changes may contribute to the elucidation of mechanisms underlying aging as well as age-related brain atrophy and disease.
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http://dx.doi.org/10.14336/AD.2017.0502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758357PMC
December 2017

Construction of Individual Morphological Brain Networks with Multiple Morphometric Features.

Front Neuroanat 2017 25;11:34. Epub 2017 Apr 25.

College of Life Science and Bioengineering, Beijing University of TechnologyBeijing, China.

In recent years, researchers have increased attentions to the morphological brain network, which is generally constructed by measuring the mathematical correlation across regions using a certain morphometric feature, such as regional cortical thickness and voxel intensity. However, cerebral structure can be characterized by various factors, such as regional volume, surface area, and curvature. Moreover, most of the morphological brain networks are population-based, which has limitations in the investigations of individual difference and clinical applications. Hence, we have extended previous studies by proposing a novel method for realizing the construction of an individual-based morphological brain network through a combination of multiple morphometric features. In particular, interregional connections are estimated using our newly introduced feature vectors, namely, the Pearson correlation coefficient of the concatenation of seven morphometric features. Experiments were performed on a healthy cohort of 55 subjects (24 males aged from 20 to 29 and 31 females aged from 20 to 28) each scanned twice, and reproducibility was evaluated through test-retest reliability. The robustness of morphometric features was measured firstly to select the more reproducible features to form the connectomes. Then the topological properties were analyzed and compared with previous reports of different modalities. Small-worldness was observed in all the subjects at the range of the entire network sparsity (20-40%), and configurations were comparable with previous findings at the sparsity of 23%. The spatial distributions of the hub were found to be significantly influenced by the individual variances, and the hubs obtained by averaging across subjects and sparsities showed correspondence with previous reports. The intraclass coefficient of graphic properties (clustering coefficient = 0.83, characteristic path length = 0.81, betweenness centrality = 0.78) indicates the robustness of the present method. Results demonstrate that the multiple morphometric features can be applied to form a rational reproducible individual-based morphological brain network.
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http://dx.doi.org/10.3389/fnana.2017.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403938PMC
April 2017

Structural MRI-based detection of Alzheimer's disease using feature ranking and classification error.

Comput Methods Programs Biomed 2016 Dec 26;137:177-193. Epub 2016 Sep 26.

Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan.

Background And Objective: This paper presents an automatic computer-aided diagnosis (CAD) system based on feature ranking for detection of Alzheimer's disease (AD) using structural magnetic resonance imaging (sMRI) data.

Methods: The proposed CAD system is composed of four systematic stages. First, global and local differences in the gray matter (GM) of AD patients compared to the GM of healthy controls (HCs) are analyzed using a voxel-based morphometry technique. The aim is to identify significant local differences in the volume of GM as volumes of interests (VOIs). Second, the voxel intensity values of the VOIs are extracted as raw features. Third, the raw features are ranked using a seven-feature ranking method, namely, statistical dependency (SD), mutual information (MI), information gain (IG), Pearson's correlation coefficient (PCC), t-test score (TS), Fisher's criterion (FC), and the Gini index (GI). The features with higher scores are more discriminative. To determine the number of top features, the estimated classification error based on training set made up of the AD and HC groups is calculated, with the vector size that minimized this error selected as the top discriminative feature. Fourth, the classification is performed using a support vector machine (SVM). In addition, a data fusion approach among feature ranking methods is introduced to improve the classification performance.

Results: The proposed method is evaluated using a data-set from ADNI (130 AD and 130 HC) with 10-fold cross-validation. The classification accuracy of the proposed automatic system for the diagnosis of AD is up to 92.48% using the sMRI data.

Conclusions: An automatic CAD system for the classification of AD based on feature-ranking method and classification errors is proposed. In this regard, seven-feature ranking methods (i.e., SD, MI, IG, PCC, TS, FC, and GI) are evaluated. The optimal size of top discriminative features is determined by the classification error estimation in the training phase. The experimental results indicate that the performance of the proposed system is comparative to that of state-of-the-art classification models.
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http://dx.doi.org/10.1016/j.cmpb.2016.09.019DOI Listing
December 2016

Combined detection of plasma miR-127-3p and HE4 improves the diagnostic efficacy of breast cancer.

Cancer Biomark 2017 ;18(2):143-148

Objective: To explore the diagnostic value of combined detection of plasma miR-127-3p and HE4 for breast cancer (BC).

Methods: Included in this study were 102 patients with pathologically confirmed BC who received treatment in the affiliated hospital of Nantong University between March 2015 and April 2016, 87 patients with benign breast tumors, and 90 healthy volunteers as control. Plasma miR-127-3p was detected by SYBR Green RT-qPCR, and plasma HE4 was detected by chemiluminescent immunoassay. The diagnostic efficacy of miR-127-3p alone, HE4 alone and combined detection of miR-127-3p and HE4 in BC women patients was evaluated by ROC curve analysis.

Results: The relative expression quantity (RQ) of plasma miR-127-3p and HE4 in BC patients was 13.561 (3.345∼18.281) pmol/L and 105.42 (40.28∼156.31) pmol/L. The RQ of plasma miR-127-3p in BC patients was significantly higher than that in benign breast tumor patients and healthy individuals (both P< 0.001), and there was no significant difference between benign breast tumor patients and healthy individuals (P> 0.05). There was no significant correlation between plasma miR-127-3p and HE4 levels (r2= 0.086, P= 0.471). ROC curve analysis on the diagnostic efficacy of plasma miR-127-3p and HE4 in BC diagnosis showed that the cut-off value of miR-127-3p and HE4 in BC diagnosis was 3.471 and 63.21 pmol/L; AUC was 0.767 and 0.670; sensitivity was 78.2% and 64.6%; specificity was 79.1% and 69.3%; accuracy was 73.2% and 65.1%, respectively. Prediction probability (P) obtained from the miR-127-3p and HE4 model established by logistic regression was P= 1/ [1 + exp (-0.142miR-127-3p-0.024HE4 + 2.875)]. AUC calculated from ROC was 0.825 and the sensitivity was increased to 87.4%.

Conclusion: Combined detection of plasma miR-127-3p and HE4 greatly improved the sensitivity of BC diagnosis and may prove to be a candidate biomarker for early detection and diagnosis of BC.
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http://dx.doi.org/10.3233/CBM-160024DOI Listing
March 2017

Role of reactive oxygen species-mediated MAPK and NF-κB activation in polygonatum cyrtonema lectin-induced apoptosis and autophagy in human lung adenocarcinoma A549 cells.

J Biochem 2016 Dec 18;160(6):315-324. Epub 2016 Jun 18.

School of Life Sciences and Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.

Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin isolated from the rhizomes of Polygonatum cyrtonema Hua, has been reported to possess remarkable anti-tumour effects via inducing apoptosis and autophagy. The aim of this study was to investigate the molecular mechanisms mediating PCL-induced apoptosis and autophagy in A549 cells. Herein, we found that the treatment of A549 cells with PCL caused a remarkable generation of reactive oxygen species (ROS) and ROS scavenger N-acetyl-cysteine (NAC) inhibited PCL-induced apoptosis and autophagy. In addition, PCL treatment activated mitogen-activated protein kinase (MAPK) members extracellular signal-regulated kinase (ERK), JNK and p38, JNK inhibitor and p38 inhibitor partially reduced PCL-induced apoptosis and autophagy. Moreover, PCL administration activated NF-κB survival pathway in A549 cells, NF-κB inhibitor Bay11-7082 promoted PCL-induced apoptosis. Importantly, we found PCL may bind to the cell surface in a mannose-specific manner, and was then internalized and accumulated primarily onto the mitochondria. These findings may provide a new perspective of PCL as a potential anti-tumour drug targeting apoptosis and autophagy pathways for future cancer therapeutics.
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http://dx.doi.org/10.1093/jb/mvw040DOI Listing
December 2016

Thalamic segmentation based on improved fuzzy connectedness in structural MRI.

Comput Biol Med 2015 Nov 12;66:222-34. Epub 2015 Sep 12.

College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022, China.

Thalamic segmentation serves an important function in localizing targets for deep brain stimulation (DBS). However, thalamic nuclei are still difficult to identify clearly from structural MRI. In this study, an improved algorithm based on the fuzzy connectedness framework was developed. Three-dimensional T1-weighted images in axial orientation were acquired through a 3D SPGR sequence by using a 1.5 T GE magnetic resonance scanner. Twenty-five normal images were analyzed using the proposed method, which involved adaptive fuzzy connectedness combined with confidence connectedness (AFCCC). After non-brain tissue removal and contrast enhancement, the seed point was selected manually, and confidence connectedness was used to perform an ROI update automatically. Both image intensity and local gradient were taken as image features in calculating the fuzzy affinity. Moreover, the weight of the features could be automatically adjusted. Thalamus, ventrointermedius (Vim), and subthalamic nucleus were successfully segmented. The results were evaluated with rules, such as similarity degree (SD), union overlap, and false positive. SD of thalamus segmentation reached values higher than 85%. The segmentation results were also compared with those achieved by the region growing and level set methods, respectively. Higher SD of the proposed method, especially in Vim, was achieved. The time cost using AFCCC was low, although it could achieve high accuracy. The proposed method is superior to the traditional fuzzy connectedness framework and involves reduced manual intervention in time saving.
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http://dx.doi.org/10.1016/j.compbiomed.2015.09.002DOI Listing
November 2015

Rheumatoid Factor, Anti-Cyclic Citrullinated Peptide Antibody, C-Reactive Protein, and Erythrocyte Sedimentation Rate for the Clinical Diagnosis of Rheumatoid Arthritis.

Lab Med 2015 ;46(3):226-9

Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, China

Objective: To explore the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, C-reactive protein (CRP), and the erythrocyte sedimentation rate (ESR) in the diagnosis of rheumatoid arthritis (RA).

Methods: Using rate nephelometry, chemiluminescence microparticle immunoassay (CMIA), and Westergren sedimentation rate testing, we detected RF, anti-CCP antibody, CRP, and ESR in 134 patients with RA and 50 healthy control individuals.

Results: We observed significant differences in RF, anti-CCP antibody, CRP, and ESR concentrations between the RA and control groups (P <.01). The sensitivity, specificity and accuracy in the diagnosis of RA were 91.0%, 74.4%, and 87.0%, respectively, for RF; 88.0%, 90.4%, and 88.1%, respectively, for anti-CCP antibody; and 90.2%, 83.3%, and 89.5%, respectively, for the detection of RA via the combination of RF and anti-CCP antibody.

Conclusion: Anti-CCP is more specific than the other parameters we reviewed for the diagnosis of RA. Combined detection of the 4 parameters is beneficial when confirming a diagnosis of RA.
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http://dx.doi.org/10.1309/LMZYTSO5RHIHV93TDOI Listing
July 2016

Stress decay, imaging plane, and gas bubble need to be considered when using ultrasound strain elastography to monitor hepatic ablations.

Acad Radiol 2015 Feb;22(2):265

College of Life Science and Bioengineering, Beijing University of Technology, Pingleyuan No.100, Chaoyang District, Beijing, China 100124; Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

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http://dx.doi.org/10.1016/j.acra.2014.08.018DOI Listing
February 2015

A survey of ultrasound elastography approaches to percutaneous ablation monitoring.

Proc Inst Mech Eng H 2014 Oct 20;228(10):1069-82. Epub 2014 Oct 20.

Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan Medical Image Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan.

Percutaneous thermal ablation has been widely used as a minimally invasive treatment for tumors. Treatment monitoring is essential for preventing complications while ensuring treatment efficacy. Mechanical testing measurements on tissue reveal that tissue stiffness increases with temperature and ablation duration. Different types of imaging methods can be used to monitor ablation procedures, including temperature or thermal strain imaging, strain imaging, modulus imaging, and shear modulus imaging. Ultrasound elastography demonstrates the potential to become the primary imaging modality for monitoring percutaneous ablation. This review briefly presented the state-of-the-art ultrasound elastography approaches for monitoring radiofrequency ablation and microwave ablation. These techniques were divided into four groups: quasi-static elastography, acoustic radiation force elastography, sonoelastography, and applicator motion elastography. Their advantages and limitations were compared and discussed. Future developments were proposed with respect to heat-induced bubbles, tissue inhomogeneities, respiratory motion, three-dimensional monitoring, multi-parametric monitoring, real-time monitoring, experimental data center for percutaneous ablation, and microwave ablation monitoring.
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http://dx.doi.org/10.1177/0954411914554438DOI Listing
October 2014

Brain differences in first-episode schizophrenia treated with quetiapine: a deformation-based morphometric study.

Psychopharmacology (Berl) 2015 Jan 2;232(2):369-77. Epub 2014 Aug 2.

College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100022, China.

Rationale: With the development of various imaging techniques, the deformation-based morphometry (DBM) method provides an objective automatic examination of the whole brain.

Objectives: This study aims to assess the abnormalities in the brains of first-episode schizophrenia (FES) patients treated with quetiapine using another advanced nonrigid registration method, hierarchical attribute matching mechanism for elastic registration, through the application of DBM in the entire brain.

Methods: Thirty FES patients and 30 normal controls were grouped by age and handedness and subjected to magnetic resonance imaging examination. The patients had relatively short durations of untreated psychosis (DUP; 6.4 ± 5.2 months), and only a single antipsychotic drug, quetiapine (dosage, 200 ± 75 mg), was used for treatment. Statistically significant changes in regional volume were analyzed via DBM. In addition, a voxel-wise analysis of correlations between the duration of treatment or dosage and volume was also performed.

Results: Compared with control subjects, FES patients showed contracted regions located in Brodmann area (BA) 42 and BA 19. By contrast, expanded regions were observed in BA 38, BA 21, BA 6 and 8, and left cerebellum. A negative correlation was observed between dosage and volume in the hippocampus, while a positive correlation was found in the caudate. Meanwhile, a negative correlation was observed between duration of treatment and volume in BA 38.

Conclusion: Both regional volume reductions and increases were detected in the brains of FES patients treated with quetiapine compared with healthy control subjects. Such differences may be partially relevant to dosage and treatment duration in clinic.
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http://dx.doi.org/10.1007/s00213-014-3670-7DOI Listing
January 2015

Susceptibility of opportunistic Burkholderia glumae to copper surfaces following wet or dry surface contact.

Molecules 2014 Jul 9;19(7):9975-85. Epub 2014 Jul 9.

Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.

Burkholderia glumae has been proposed to have a potential risk to vulnerable communities. In this work, we investigated the antibacterial activity and mechanism of copper surfaces against multi-drug resistant B. glumae from both patients and rice plants. The susceptibility of B. glumae to copper surfaces was noted by a significant decline in viable bacterial counts, relative to the slight reduction of stainless steel and polyvinylchloride, both of which were used as control surfaces. The mode of action of bacterial killing was determined by examing the mutagenicity, DNA damage, copper ions accumulation, and membrane damage in bacterial cells. The results indicated that the cells exposed to copper surfaces did not cause severe DNA lesions or increase the mutation frequencies, but resulted in a loss of cell membrane integrity within minutes. Furthermore, bacterial cells exposed to copper surfaces accumulated significantly higher amounts of copper compared to control surfaces. Overall, this study showed that metallic copper had strong antibacterial effect against B. glumae by causing DNA and membrane damage, cellular accumulation of copper, and cell death following DNA degradation, which could be utilized to reduce the risk of bacterial contamination and infection.
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http://dx.doi.org/10.3390/molecules19079975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271097PMC
July 2014

Inhibitory effect and mode of action of chitosan solution against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae RS-1.

Carbohydr Res 2014 Jun 5;391:48-54. Epub 2014 Mar 5.

State Key Laboratory Breeding Base for Zhejiang Sustainable Plant Pest and Disease Control, Zhejiang Academy of Agricultural Sciences, 310021 Hangzhou, China. Electronic address:

Inhibitory effect and mode of action of chitosan solution against rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) strain RS-1 was examined in this study. Result from this study indicated that chitosan solutions at 0.10, 0.20, and 0.40mg/mL inhibited the in vitro growth of Aaa strain RS-1, and in general the inhibitory efficiency increased with the increase of both chitosan concentration and the incubation time. Antibacterial activity of chitosan in this study may be mainly due to the damage of cell membrane, which was evidenced by both the cell lysis observed by transmission electron microscopy, and the increased release of cell materials based on the measurement of cell membrane integrity. Furthermore, chitosan solutions at concentrations of 0.1, 0.2, and 0.4mg/mL markedly inhibited bacterial biofilm formation compared to the control, and the inhibitory effect increased with the increase of chitosan concentration. In addition, quantitative real-time PCR of the 10 secretion system related genes revealed the differential expression of genes in particular ompA/motB, emphasizing the importance of this gene in the response of Aaa strain RS-1 to chitosan stress. These results indicated that the antibacterial mode of action of chitosan may be mainly due to membrane disruption and lysis, reduction of biofilm formation, and gene expression change. Overall, the results clearly indicated that chitosan had the potential to control bacterial brown stripe of rice.
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http://dx.doi.org/10.1016/j.carres.2014.02.025DOI Listing
June 2014
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