Publications by authors named "Yixing Wang"

48 Publications

A CT-based radiomics model to predict subsequent brain metastasis in patients with ALK-rearranged non-small cell lung cancer undergoing crizotinib treatment.

Thorac Cancer 2022 Apr 18. Epub 2022 Apr 18.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: Brain metastasis (BM) comprises the most common reason for crizotinib failure in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We hypothesize that its occurrence could be predicted by a computed tomography (CT)-based radiomics model, therefore, allowing for selection of enriched patient populations for prevention therapies.

Methods: A total of 75 eligible patients were enrolled from Sun Yat-sen University Cancer Center between June 2014 and September 2019. The primary endpoint was brain metastasis-free survival (BMFS), estimated from the initiation of crizotinib to the date of the occurrence of BM. Patients were randomly divided into two cohorts for model training (n = 51) and validation (n = 24), respectively. A radiomics signature was constructed based on features extracted from chest CT before crizotinib treatment. Clinical model was developed using the Cox proportional hazards model. Log-rank test was performed to describe the difference of BMFS risk.

Results: Patients with low radiomics score had significantly longer BMFS than those with higher, both in the training cohort (p = 0.019) and validation cohort (p = 0.048). The nomogram combining smoking history and the radiomics signature showed good performance for the estimation of BMFS, both in the training (concordance index [C-index], 0.762; 95% confidence interval [CI], 0.663-0.861) and validation cohort (C-index, 0.724; 95% CI, 0.601-0.847).

Conclusion: We have developed a CT-based radiomics model to predict subsequent BM in patients with non-brain metastatic NSCLC undergoing crizotinib treatment. Selection of an enriched patient population at high BM risk will facilitate the design of clinical trials or strategies to prevent BM.
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http://dx.doi.org/10.1111/1759-7714.14386DOI Listing
April 2022

Identification of a SARS-CoV-2 virus-encoded small non-coding RNA in association with the neurological disorders in COVID-19 patients.

Signal Transduct Target Ther 2022 Mar 31;7(1):107. Epub 2022 Mar 31.

Key Laboratory of Arrhythmias of the Ministry of Education, Research Center for Translational Medicine, Heart Failure Institute, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1038/s41392-022-00969-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967939PMC
March 2022

Optimizing the tumor shrinkage threshold for evaluating immunotherapy efficacy for advanced non-small-cell lung cancer.

J Cancer Res Clin Oncol 2022 Mar 18. Epub 2022 Mar 18.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Purpose: The rise of immune checkpoint inhibitors (ICIs) in recent years has coincided with unusual clinical response patterns. Modification of the sum of longest diameters (SLD)-based threshold that reflecting dynamic change of the tumor burden and predicting response to ICIs, may markedly improve current treatment regimens.

Methods: The baseline and post-treatment SLD of target lesion was recorded and the maximum percent change of the SLD from baseline was designated as SLD-change score. The optimal cut-off value was obtained using the X-tile program. The relationship between SLD-change score and survival outcome (PFS, OS) was evaluated.

Results: 10% cut-off value of SLD-change score was found to be most distinctive for PFS. Responders defined according to this cut-off value showed a significant improvement for PFS and OS. Bone metastasis and brain metastasis were also two independent prognostic factors of PFS and OS, respectively.

Conclusions: 10% SLD change score could discriminate for ICIs treatment response, which holds great promise in promoting the development of precise immunotherapeutic strategy.
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http://dx.doi.org/10.1007/s00432-022-03978-3DOI Listing
March 2022

Assessment of sarcopenia as a predictor of poor overall survival for advanced non-small-cell lung cancer patients receiving salvage anti-PD-1 immunotherapy.

Ann Transl Med 2021 Dec;9(24):1801

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: Sarcopenia, which is defined as the loss of skeletal muscle mass, has been identified as a poor prognostic factor for cancer patients. This study sought to elucidate the effects of sarcopenia on the outcomes of advanced non-small cell lung cancer (NSCLC) patients receiving salvage anti-programmed death-1 (PD-1) immunotherapy.

Methods: In total, 105 NSCLC patients receiving second-line anti-PD-1 immunotherapy at the Sun Yat-sen University Cancer Center between January 2015 and December 2017 were enrolled in this study, and detailed patient data were collected. Available lumbar computed tomography images of the patients were analyzed to determine the total skeletal muscle cross-section area. The efficacy of the predictive and prognostic role of sarcopenia in progression-free survival (PFS) and overall survival (OS) was analyzed using the Kaplan-Meier method, and the risk factors were analyzed using Cox analyses.

Results: We found that patients with sarcopenia receiving salvage anti-PD-1 immunotherapy had significantly worse PFS (2.67 . 7.96 months; P<0.001) and OS (9.08 . 21.84 months; P<0.001) than their non-sarcopenic counterparts. We also found that sarcopenia was associated with the neutrophil-to-lymphocyte ratio (NLR) (P=0.041), and that the NLR acts as a predictor of OS.

Conclusions: Sarcopenia was associated with a poor prognosis in advanced NSCLC patients receiving salvage anti-PD-1 immunotherapy. Further research needs to be conducted to identify more biomarkers and the patients most likely to benefit from immunotherapy.
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http://dx.doi.org/10.21037/atm-21-6578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756219PMC
December 2021

Reducing number of target lesions for RECIST1.1 to predict survivals in patients with advanced non-small-cell lung cancer undergoing anti-PD1/PD-L1 monotherapy.

Lung Cancer 2021 Dec 31;165:10-17. Epub 2021 Dec 31.

State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Objectives: The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 provides conventional and standardized response assessment for multiple solid tumors. We investigated the smallest number of target lesions that can be measured without compromising response categorization and survival prediction in patients with advanced non-small-cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 monotherapy.

Material And Methods: 125 aNSCLC patients with at least two measurable lesions undergoing PD-1/PD-L1 inhibitor treatment were retrospectively studied. Tumor measurements allowing up to two lesions per organ and five lesions in total were reviewed. Inter-individual agreement and κ values for inter-method concordance on response status were evaluated based on up to five target lesions versus the largest one through four lesions. C-index was calculated to evaluate the prognostic accuracy of response categorization based on the selected number of target lesions for predicting overall survival (OS). Cox regression analysis was conducted for survival analysis.

Results: The highly consistent response assignment (99.2%) could be obtained when measuring the largest two lesions versus up to five lesions. Using the largest two through four lesions produced κ values of 0.986, 1.000 and 1.000 for response assessment, values significantly higher than those obtained when measuring the largest single lesion (κ = 0.850). C-index for overall survival (OS) was similar when assessing the largest one through five lesions, ranging from 0.646 to 0.654. Cox regression analyses showed that radiological response significantly predicted OS, irrespective of the number of target lesions selected.

Conclusions: Reducing the number of target lesions does not affect OS prediction in aNSCLC patients treated with anti-PD-1/PD-L1 therapy. Considering the high intra-individual and inter-method concordance, using the largest two lesions in total is proposed to assess response.
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http://dx.doi.org/10.1016/j.lungcan.2021.12.015DOI Listing
December 2021

Dietary plant sterols prevented cholesterol gallstone formation in mice.

Food Funct 2021 Nov 29;12(23):11829-11837. Epub 2021 Nov 29.

Center of Gallstone Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of Medicine, Shanghai, 201200, China.

Cholesterol gallstone disease is a common global condition. This study investigated the role of plant sterols (PS) in the prevention of gallstone formation and the underlying mechanisms. Adult male mice were fed a lithogenic diet (LD) alone or supplemented with PS (LD-ps), phospholipids (LD-pl) or both PS and phospholipids (LD-ps/pl) for 8 weeks. Incidences of gallstone formation were compared among the groups. Lipids in the bile, liver and serum were analyzed. The expression of genes involved in cholesterol absorption, transport and metabolism in the liver and small intestine was determined. The incidences of gallstone formation were 100% (10/10), 20% (2/10), 100% (10/10) and 40% (4/10) in the LD, LD-ps, LD-pl and LD-ps/pl groups, respectively. Serum cholesterol and intestinal cholesterol absorption were decreased in PS-supplemented mice. The expression of genes related to cholesterol transport and metabolism in the liver was down-regulated by dietary PS. PS supplementation decreased Niemann-Pick C1-like 1 expression in the small intestine and reduced intestinal cholesterol absorption. Our results demonstrated that PS could inhibit intestinal cholesterol absorption and thus prevent cholesterol gallstone formation.
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http://dx.doi.org/10.1039/d1fo02695jDOI Listing
November 2021

Ultrafast Water Transport in Two-Dimensional Channels Enabled by Spherical Polyelectrolyte Brushes with Controllable Flexibility.

Angew Chem Int Ed Engl 2021 Sep 3;60(36):19933-19941. Epub 2021 Aug 3.

State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, No.130 Meilong Road, Shanghai, 200237, China.

Fast water transport channels are crucial for water-related membrane separation processes. However, overcoming the trade-off between flux and selectivity is still a major challenge. To address this, we constructed spherical polyelectrolyte brush (SPB) structures with a highly hydrophilic polyelectrolyte brush layer, and introduced them into GO laminates, which increased both the flux and the separation factor. At 70 °C, the flux reached 5.23 kg m  h , and the separation factor of butanol/water increased to ≈8000, which places it among the most selective separation membranes reported to date. Interestingly, further studies demonstrated that the enhancement of water transport was not only dependent on the hydrophilicity of the polyelectrolyte chains, but also influenced by their flexibility in the solvent. Quartz crystal microbalance with dissipation and molecular dynamics simulations revealed the structure-performance correlations between water molecule migration and the flexibility of the ordered polymer chains in the 2D confined space.
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http://dx.doi.org/10.1002/anie.202107085DOI Listing
September 2021

A Metabolite Array Technology for Precision Medicine.

Anal Chem 2021 04 2;93(14):5709-5717. Epub 2021 Apr 2.

Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

The application of metabolomics in translational research suffers from several technological bottlenecks, such as data reproducibility issues and the lack of standardization of sample profiling procedures. Here, we report an automated high-throughput metabolite array technology that can rapidly and quantitatively determine 324 metabolites including fatty acids, amino acids, organic acids, carbohydrates, and bile acids. Metabolite identification and quantification is achieved using the Targeted Metabolome Batch Quantification (TMBQ) software, the first cross-vendor data processing pipeline. A test of this metabolite array was performed by analyzing serum samples from patients with chronic liver disease ( = 1234). With high detection efficiency and sensitivity in serum, urine, feces, cell lysates, and liver tissue samples and suitable for different mass spectrometry systems, this metabolite array technology holds great potential for biomarker discovery and high throughput clinical testing. Additionally, data generated from such standardized procedures can be used to generate a clinical metabolomics database suitable for precision medicine in next-generation healthcare.
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http://dx.doi.org/10.1021/acs.analchem.0c04686DOI Listing
April 2021

Bile Acid Profiles Are Distinct among Patients with Different Etiologies of Chronic Liver Disease.

J Proteome Res 2021 05 23;20(5):2340-2351. Epub 2021 Mar 23.

Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

A significant increase of bile acid (BA) levels has been recognized as a general metabolic phenotype of diverse liver diseases. Monitoring of BA profiles has been proposed for etiology differentiation on liver injury. Here, we quantitatively profiled serum BAs of healthy controls and 719 patients with chronic liver disease of five etiologies, hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH), alcohol-induced liver disease (ALD), and primary biliary cirrhosis (PBC), and investigated the generality and specificity of different etiologies. The raw data have been deposited into MetaboLights (ID: MTBLS2459). We found that patients with HBV, HCV, and NASH appeared to be more similar, and ALD and PBC patients clustered together. BA profiles, consisting of a total concentration of the 21 quantified BAs [total BAs (TBAs)], 21 BA proportions, and 24 BA relevant variables, were highly different among the etiologies. Specifically, the total BAs was higher in ALD and PBC patients compared with the other three groups. The proportion of conjugated deoxycholates was the highest in HBV-infected patients. The ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs was the highest in NASH patients. The proportion of taurine-conjugated BAs was the highest in ALD patients. For PBC patients, the proportion of ursodeoxycholate species was the highest, and the ratio of primary to secondary BAs was the lowest. Comparatively, the difference of BA profiles among cirrhosis patients was consistent but weaker than that of all patients. The correlations between BA profiles and clinical indices were also quite different in different pathological groups, both in all patients and in patients with cirrhosis. Overall, our findings suggested that BA compositions are distinct among patients with different etiologies of chronic liver disease, and some BA-relevant variables are of clinical potentials for liver injury type differentiation, although further validations on more etiologies and populations are needed.
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http://dx.doi.org/10.1021/acs.jproteome.0c00852DOI Listing
May 2021

Effect and related mechanism of Yinchenhao decoction on mice with lithogenic diet-induced cholelithiasis.

Exp Ther Med 2021 Apr 3;21(4):316. Epub 2021 Feb 3.

Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Clinical Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, P.R. China.

The aim of the present study was to investigate the effects and the underlying mechanisms of Yinchenhao Decoction (YCHD), a traditional Chinese medicine formulation, on C57BL/6 mice with lithogenic diet (LD)-induced cholelithiasis. The condition of cholelithiasis was evaluated using a six-level criteria. Levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in the serum and liver tissue were measured using enzyme colorimetry. Concentrations of TC, phospholipids (PL) and total bile acids (TBA) in the bile were measured to calculate the cholesterol saturation index. Liver histopathology was microscopically observed and mRNA expression levels of ABCG5, ABCG8, SRBI, ABCB4, ABCB11 and NPC1L1 involved in cholesterol metabolism were measured using reverse transcription-quantitative PCR. The results showed that feeding mice the LD induced cholelithiasis, along with abnormal serum biochemical indices and imbalances in biliary cholesterol homeostasis. Increased ALT and ALP levels in the serum and ALT, ALP, TC and LDL-C levels in the serum and liver indicated the existence of hepatocyte injury, which were consistent with the pathological changes. YCHD treatment ameliorated the serum and hepatic biochemical abnormalities and adjusted the biliary imbalance. In addition, elevated expression of ATP-binding cassette subfamily G member 5/8, scavenger receptor class B type I and Niemann-Pick C1 Like 1 in the liver and small intestine were observed at the onset of cholelithiasis but were reversed by YCHD. Taken together, results from the present study suggest that YCHD ameliorated LD-induced cholelithiasis mice, which may be caused by improvements in biliary cholesterol supersaturation and regulation of cholesterol metabolism.
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http://dx.doi.org/10.3892/etm.2021.9747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885065PMC
April 2021

Real World First-Line Treatments and Outcomes of Nab-Paclitaxel Plus Gemcitabine, mFOLFIRINOX and GEMOX in Unresectable Pancreatic Cancer from a Chinese Single Institution.

Curr Oncol 2020 12 30;28(1):209-219. Epub 2020 Dec 30.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients.

Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed.

Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine ( = 62), mFOLFIRINOX ( = 30) or GEMOX ( = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months ( = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups.

Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.
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http://dx.doi.org/10.3390/curroncol28010023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816170PMC
December 2020

Stratification of Estrogen Receptor-Negative Breast Cancer Patients by Integrating the Somatic Mutations and Transcriptomic Data.

Front Genet 2021 3;12:610087. Epub 2021 Feb 3.

College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, China.

Patients with estrogen receptor-negative breast cancer generally have a worse prognosis than estrogen receptor-positive patients. Nevertheless, a significant proportion of the estrogen receptor-negative cases have favorable outcomes. Identifying patients with a good prognosis, however, remains difficult, as recent studies are quite limited. The identification of molecular biomarkers is needed to better stratify patients. The significantly mutated genes may be potentially used as biomarkers to identify the subtype and to predict outcomes. To identify the biomarkers of receptor-negative breast cancer among the significantly mutated genes, we developed a workflow to screen significantly mutated genes associated with the estrogen receptor in breast cancer by a gene coexpression module. The similarity matrix was calculated with distance correlation to obtain gene modules through a weighted gene coexpression network analysis. The modules highly associated with the estrogen receptor, called important modules, were enriched for breast cancer-related pathways or disease. To screen significantly mutated genes, a new gene list was obtained through the overlap of the important module genes and the significantly mutated genes. The genes on this list can be used as biomarkers to predict survival of estrogen receptor-negative breast cancer patients. Furthermore, we selected six hub significantly mutated genes in the gene list which were also able to separate these patients. Our method provides a new and alternative method for integrating somatic gene mutations and expression data for patient stratification of estrogen receptor-negative breast cancers.
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http://dx.doi.org/10.3389/fgene.2021.610087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886807PMC
February 2021

Immune Cell Infiltration of the Primary Tumor Microenvironment Predicted the Treatment Outcome of Chemotherapy With or Without Bevacizumab in Metastatic Colorectal Cancer Patients.

Front Oncol 2020 27;10:581051. Epub 2021 Jan 27.

VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: With the interest in cancer immunotherapy, it may be possible to combine immunotherapy with bevacizumab and chemotherapy. We evaluated whether tumor-infiltrating immune cells are associated with the efficacy of chemotherapy with or without bevacizumab for the treatment of metastatic colorectal cancer (mCRC).

Methods: This study enrolled mCRC patients on standard treatment with available detailed data and tumor tissue at Sun Yat-sen University Cancer Center between July 1, 2005, and October 1, 2017. CD3+ and CD8+ T cell densities examined by immunohistochemistry in both the tumor core (CT) and invasive margin (IM) were summed as the Immunoscore, and the CD8+/CD3+ T cell ratio was calculated. The predictive and prognostic efficacies of tumor-infiltrating immune cells for progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier and Cox analyses.

Results: The CD8+/CD3+ T cell ratio in the microenvironment was an independent prognostic factor for OS (28.12 mo vs. 16.56 mo, = 0.017) among the 108 studied patients. In the chemotherapy only group, patients with a high Immunoscore had a high overall response rate (ORR, 40.0% vs. 60.0%, = 0.022), those with a low CD8+/CD3+ T cell ratio in the microenvironment had a significantly longer PFS (8.64 mo vs. 6.01 mo, = 0.017), and those with a high CD3+ T cell density in the CT had a longer OS (16.56 mo vs. 25.66 mo, = 0.029). In the chemotherapy combined with bevacizumab group, patients with a higher CD8+ T cell density in the IM had a longer PFS (7.62 mo vs. 11.66 mo, = 0.034) and OS (14.55 mo vs. 23.72 mo, = 0.033).

Conclusion: Immune cells in primary tumors play an important role in predicting mCRC treatment efficacy. CD8 predicts the effect of bevacizumab plus chemotherapy, while CD3 and CD8/CD3 predict chemotherapy efficacy.
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http://dx.doi.org/10.3389/fonc.2020.581051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873592PMC
January 2021

Acupoint Catgut Embedding as Adjunctive Therapy for Patients With Gallstones.

J Clin Gastroenterol 2022 01;56(1):e77-e83

Graduate School, Shanghai University of Traditional Chinese Medicine.

Aims Of This Study: A randomized clinical trial was undertaken to investigate the efficacy of acupoint catgut embedding (ACE) as adjunctive therapy to tauroursodeoxycholic acid (TUDCA) therapy on gallbladder emptying and clinical symptoms in patients with gallstone disease.

Materials And Methods: Between August 2018 and January 2019, 70 patients with gallstones in our hospital were enrolled in this prospective clinical trial. All the patients were randomly divided into the ACE group (ACE+TUDCA treatment for 8 wk) and the Sham group (Sham ACE+TUDCA treatment for 8 wk). In the ACE group, all the patients were nightly given ACE every 2 weeks, and in 2 groups, every patient took TUDCA 500 mg at bedtime. The parameters about gallbladder emptying were detected by ultrasound before and after the treatment, and the clinical symptom scores were recorded at the same time points.

Results: A total of 63 patients with gallstone disease were included in our study, with 33 patients in the ACE group and 30 patients in the Sham group. In the ACE group, the empty volume (EV) and gallbladder ejection fraction (GBEF) were improved after treatment (P<0.05). Almost every symptom score (except symptom 7, P=0.15) and total score were decreased (P<0.05). In the Sham group, the symptom 1, 2, 4, 5 scores, and total score were significantly decreased (P<0.05). Moreover, the residual volume in the ACE group was significantly lower than in the Sham group (P=0.008). The EV and GBEF in the ACE group were higher than that in the Sham group (P<0.05). The score of symptom 6 in the ACE group was lower than that in the Sham group (P=0.008).

Conclusion: ACE therapy could more effectively improve the gallbladder emptying with a shorter treatment course. Therefore, ACE+TUDCA therapy might be a time-saving treatment for gallstones.
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http://dx.doi.org/10.1097/MCG.0000000000001487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647692PMC
January 2022

K-Module Algorithm: An Additional Step to Improve the Clustering Results of WGCNA Co-Expression Networks.

Genes (Basel) 2021 01 12;12(1). Epub 2021 Jan 12.

College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin 150001, China.

Among biological networks, co-expression networks have been widely studied. One of the most commonly used pipelines for the construction of co-expression networks is weighted gene co-expression network analysis (WGCNA), which can identify highly co-expressed clusters of genes (modules). WGCNA identifies gene modules using hierarchical clustering. The major drawback of hierarchical clustering is that once two objects are clustered together, it cannot be reversed; thus, re-adjustment of the unbefitting decision is impossible. In this paper, we calculate the similarity matrix with the distance correlation for WGCNA to construct a gene co-expression network, and present a new approach called the k-module algorithm to improve the WGCNA clustering results. This method can assign all genes to the module with the highest mean connectivity with these genes. This algorithm re-adjusts the results of hierarchical clustering while retaining the advantages of the dynamic tree cut method. The validity of the algorithm is verified using six datasets from microarray and RNA-seq data. The k-module algorithm has fewer iterations, which leads to lower complexity. We verify that the gene modules obtained by the k-module algorithm have high enrichment scores and strong stability. Our method improves upon hierarchical clustering, and can be applied to general clustering algorithms based on the similarity matrix, not limited to gene co-expression network analysis.
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http://dx.doi.org/10.3390/genes12010087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828115PMC
January 2021

High efficient reduction of 4-nitrophenol and dye by filtration through Ag NPs coated PAN-Si catalytic membrane.

Chemosphere 2021 Jan 26;263:127995. Epub 2020 Aug 26.

State Key Laboratory of Chemical Engineering, Membrane Science and Engineering R&D Lab, Chemical Engineering Research Center, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.

Catalytic membrane plays an important role in environmental remedy. In this study, we reported an Ag coated membrane (PAN-Si-Cu-Ag) with a high catalytic activity to reduce 4-nitrophenol (4-NP) and methyl orange (MO) from water. The best performance is 99% reduction degree and 280 L m.h.bar flux for (4-NP) reduction at 4-NP: NaBH = 1:50 (mM) during a 12-h filtration. The reduction degree for MO is above 90% and the flux is about 230 L m·h·bar, which is almost the best report till now. The Ag coated membrane was prepared by metal displacement-epitaxial growth on silica covalent grafted PAN membrane (PAN-Si). Silica atoms were used as linker to ensure the good adhesion between polymer and metal NPs, the loss amount of Ag NPs from the coated catalytic membrane is loss about 2 μg/cm after one month storage. Cheap metal NPs were firstly reduced on the surface of PAN-Si membrane and then used to displace Ag ions. Thus the obtained catalytic membrane showed a very high loading (28%). Finally, the catalytic filtration mechanism of 4-NP was distinguished by Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and adsorption measurement.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127995DOI Listing
January 2021

Herring egg phosphopeptides as calcium carriers for improving calcium absorption and bone microarchitecture in vivo.

Food Funct 2020 Dec 27;11(12):10936-10944. Epub 2020 Nov 27.

National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China.

Phosphorylation may enhance the functional properties of proteins/peptides. Herring egg phosphopeptides (HEPPs) have been found to be more effective than the non-phosphorylated variant in calcium-binding activities due to the introduced phosphate groups. However, whether HEPPs as calcium carriers will be superior to herring egg peptides (HEPs) in improving calcium bioavailability in vivo, for the equivalent calcium intake prerequisite, remains to be clarified. This study aimed to evaluate the effect of HEPPs-calcium complex and HEPs-calcium complex on calcium absorption and bioavailability in calcium-deficient mice. Results showed that the remarkably lower calcium absorption and bone calcium deposition induced by long-term calcium deficiency were accompanied by deterioration of the trabecular bone microarchitecture (P < 0.05). The HEPPs-Ca supplements significantly improved the apparent calcium absorption, increased the serum calcium level, decreased the alkaline phosphatase activity, strengthened the bone biomechanical property, and increased bone volume/tissue volume (BV/TV) and trabecular number (Tb·N) in calcium-deficient mice (P < 0.05), as determined by micro-computed tomography (micro-CT) assay. The effect of HEPPs-Ca on calcium absorption and bioavailability was comparable to that of CPPs-Ca, but better than that of HEPs-Ca and CaCO. This study brings new insights into the potential of HEPPs as an alternative to CPPs for use in calcium supplements.
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http://dx.doi.org/10.1039/d0fo01232gDOI Listing
December 2020

High efficient dye removal with hydrolyzed ethanolamine-Polyacrylonitrile UF membrane: Rejection of anionic dye and selective adsorption of cationic dye.

Chemosphere 2020 Nov 20;259:127390. Epub 2020 Jun 20.

State Key Laboratory of Chemical Engineering, Membrane Science and Engineering R&D Lab, Chemical Engineering Research Center, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.

The dye-water treatment using UF membrane is still a challenge. In the present study, the optimized PAN-ETA ultrafiltration membrane was hydrolyzed and subsequently characterized by SEM, IR, CA, XPS, NMR, mechanic measurement, etc. The obtained membrane (H-PAN-ETA) was used for dye removal and it showed both an excellent anti-dye fouling and a good rejection property for anionic dyes. I.e. 96% rejection for methyl blue (MB), 99% for congo red (CR), 94% for acid fuchsin (AF) with no sign of contamination by dye. The flux of H-PAN-ETA membrane maintained at 50-53 L m⋅ h during a 10-h filtration, which is higher than that of tight UF membranes reported. Meanwhile, H-PAN-ETA membrane was able to selectively remove cationic dyes, such as methylene blue (MEB), rhodamine B (RB) and, crystal violet (CV), or the mixture of anionic dye/cationic dye by adsorption process. Its adsorption capacity remained unchanged after 20 cycles. Finally, the immobile electrical double layer (EDL) theory combined with electrostatic force was introduced to explain the separation mechanism of charged UF membrane, which is helpful to instruct the preparation of UF membrane for dye removal.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127390DOI Listing
November 2020

Serum metabolite profiles are associated with the presence of advanced liver fibrosis in Chinese patients with chronic hepatitis B viral infection.

BMC Med 2020 06 5;18(1):144. Epub 2020 Jun 5.

E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Background: Accurate and noninvasive diagnosis and staging of liver fibrosis are essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients.

Methods: We quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively.

Results: The panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4, and AST/ALT ratio, with both greater sensitivity and specificity.

Conclusions: Our study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression in patients with chronic hepatitis B virus infection.
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http://dx.doi.org/10.1186/s12916-020-01595-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273661PMC
June 2020

Calcium binding to herring egg phosphopeptides: Binding characteristics, conformational structure and intermolecular forces.

Food Chem 2020 Apr 8;310:125867. Epub 2019 Nov 8.

National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, PR China. Electronic address:

Phosphorylation could improve functional characteristics of proteins/peptides, and might be used in the functional improvement of herring egg peptides owing to their enriched phosphorylation sites. The present study aimed to study the effect of phosphorylation on calcium-binding ability of herring egg peptides, and investigate the conformational structure and intermolecular forces of herring egg phosphopeptides (HEPPs)-calcium complex. The HEPPs were found to be superior in calcium-binding activities, as compared to the non-phosphorylated variant. This finding might be attributed to the interaction between calcium ions and the introduced phosphate groups of HEPPs. Calcium favored the formation of β-sheet structure on the HEPPs and induced structural folding, thus assembling into spherical nanoparticles. The conformation of HEPPs-Ca nanoparticles was formed and stabilized mainly by hydrophobic interaction, hydrogen bonds and electrostatic interaction.
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http://dx.doi.org/10.1016/j.foodchem.2019.125867DOI Listing
April 2020

Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indexes.

J Immunother Cancer 2019 07 12;7(1):179. Epub 2019 Jul 12.

VIP Department, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Background: Immune cells play a key role in cancer progression and treatment. It is unclear whether the clinicopathologic characteristics and blood indexes of colorectal cancer (CRC) patients could predict immune cell concentrations in the tumor microenvironment.

Methods: CRC patients with detailed data and tumor tissue who visited Sun Yat-sen University Cancer Center between April 1, 2004, and September 1, 2017, were enrolled. The densities of CD3+ and CD8+ T cells examined by immunohistochemistry in both the core of the tumor (CT) and the invasive margin (IM) were summed as the Immunoscore. The relationships between the Immunoscore and clinicopathologic characteristics and blood indexes, including tumor biomarkers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9)), inflammatory markers (lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (ALB), neutrophils, lymphocytes, monocytes, platelets, NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and LMR (lymphocyte-to-monocyte ratio)) and lipid metabolism markers (cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB)), were analyzed using SPSS.

Results: Older patients had lower CD3+ and CD8+ T cell expression in the IM and a lower Immunoscore than did younger patients. CD8+ T cell expression in the IM and the Immunoscore were lower in right-side tumors than in left-sided tumors. High CD8+ T cell expression in the CT was found in the T4 stage group. The higher the CEA level in the blood, the fewer CD8+ T cells were in the CT. Either fewer monocytes or a higher LMR in the blood, the larger number of CD3+ T cells in the CT. The more ApoA1 was in the blood, the more CD3+ T cells were in both the CT and the IM.

Conclusion: Age, T stage, tumor location, CEA, monocytes, LMR and ApoA1 could reflect immune cells infiltrating the tumor microenvironment of CRC.
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http://dx.doi.org/10.1186/s40425-019-0656-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625045PMC
July 2019

The scrub typhus in mainland China: spatiotemporal expansion and risk prediction underpinned by complex factors.

Emerg Microbes Infect 2019 ;8(1):909-919

b The State Key Laboratory of Pathogen and Biosecurity , Beijing Institute of Microbiology and Epidemiology , Beijing , People's Republic of China.

In mainland China, a geographic northward expansion of scrub typhus has been seen, highlighting the need to understand the factors and identify the risk for disease prevention. Incidence data from 1980 to 2013 were used. A Cox proportional hazard model was used to identify drivers for spatial spread, and a boosted regression tree (BRT) model was constructed to predict potential risk areas. Since the 1980s, an invasive expansion from South Natural Foci towards North Natural Foci was clearly identified, with the epidemiological heterogeneity observed between two regions, mainly in spatial distribution, seasonality, and demographic characteristics. Survival analysis disclosed significant factors contributing to the spatial expansion as following: being intersected by freeway (HR = 1.31, 95% CI: 1.11-1.54), coverage percentage of broadleaf forest (HR = 1.10, 95% CI: 1.06-1.15), and monthly average temperature (HR = 1.27, 95% CI: 1.25-1.30). The BRT models showed that precipitation, sunshine hour, temperature, crop field, and relative humidity contributed substantially to the spatial distribution of scrub typhus. A county-scale risk map was created to predict the regions with high probability of the disease. The current study enabled a comprehensive overview of epidemiological characteristics of scrub typhus in mainland China.
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http://dx.doi.org/10.1080/22221751.2019.1631719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598543PMC
November 2019

Establishment of inflammation biomarkers-based nomograms to predict prognosis of advanced colorectal cancer patients based on real world data.

PLoS One 2018 4;13(12):e0208547. Epub 2018 Dec 4.

VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.

Purpose: To establish three novel prognostic nomograms with inflammatory factors for advanced colorectal cancer (ACRC), right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) according to real world data.

Materials And Methods: ACRC patients receiving medicine therapy from January 1st, 2005 to September 31th, 2015 in Sun Yat-sen University Cancer Center were enrolled. Inflammatory indicators such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were analyzed for establishing nomograms predicting overall survival (OS). Concordance index (C-index) determined predictive accuracy and discriminative ability.

Results: Our study selected 807 ACRC patients, 29.6% RSCC and 70.4% LSCRC. Median OS was 23.36 months. Patients at lower level of NLR, PLR, CEA, CA 19-9, LDH and CRP showed longer OS (P < 0.001). For all patients, pathological grade (P = 0.018), treatments (P = 0.042), sidedness (P = 0.003), NLR (P < 0.001), CA 19-9 (P < 0.001), LDH (P < 0.001) and CRP (P = 0.0012) contributed to OS independently. For RSCC, pathological grade (P = 0.022), CA 19-9 (P < 0.001), LDH (P < 0.001) and CRP (P = 0.001) were significantly related with OS. For LSCRC patients, treatments (cetuximab vs chemotherapy: P = 0.008; bevacizumab vs chemotherapy: P = 0.166), NLR (P < 0.001), CA 19-9 (P = 0.030) and LDH (P < 0.001) were independent factors for OS. Final models showed acceptable internal validity with C-indexes of 0.687, 0.697 and 0.667 in all, RSCC and LSCRC patients.

Conclusions: Inflammatory factors enrolled in the proposed nomograms showed accurately individualized prognostic prediction, and prognostic factors for RSCC and LSCRC were different.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208547PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279229PMC
May 2019

Clinical prediction of HBV and HCV related hepatic fibrosis using machine learning.

EBioMedicine 2018 Sep 10;35:124-132. Epub 2018 Aug 10.

University of Hawaii Cancer Center, Honolulu, HI, USA. Electronic address:

Clinical prediction of advanced hepatic fibrosis (HF) and cirrhosis has long been challenging due to the gold standard, liver biopsy, being an invasive approach with certain limitations. Less invasive blood test tandem with a cutting-edge machine learning algorithm shows promising diagnostic potential. In this study, we constructed and compared machine learning methods with the FIB-4 score in a discovery dataset (n = 490) of hepatitis B virus (HBV) patients. Models were validated in an independent HBV dataset (n = 86). We further employed these models on two independent hepatitis C virus (HCV) datasets (n = 254 and 230) to examine their applicability. In the discovery data, gradient boosting (GB) stably outperformed other methods as well as FIB-4 scores (p < .001) in the prediction of advanced HF and cirrhosis. In the HBV validation dataset, for classification between early and advanced HF, the area under receiver operating characteristic curves (AUROC) of GB model was 0.918, while FIB-4 was 0.841; for classification between non-cirrhosis and cirrhosis, GB showed AUROC of 0.871, while FIB-4 was 0.830. Additionally, GB-based prediction demonstrated good classification capacity on two HCV datasets while higher cutoffs for both GB and FIB-4 scores were required to achieve comparable specificity and sensitivity. Using the same parameters as FIB-4, the GB-based prediction system demonstrated steady improvements relative to FIB-4 in HBV and HCV cohorts with different cutoff values required in different etiological groups. A user-friendly web tool, LiveBoost, makes our prediction models freely accessible for further clinical studies and applications.
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http://dx.doi.org/10.1016/j.ebiom.2018.07.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154783PMC
September 2018

Effect and Mechanism of ShiZhiFang on Uric Acid Metabolism in Hyperuricemic Rats.

Evid Based Complement Alternat Med 2018 25;2018:6821387. Epub 2018 Jun 25.

Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (14DZ2273200), No. 528 Road Zhangheng, Shanghai 201203, China.

Objective: To explore the effect and mechanism of ShiZhiFang on uric acid metabolism.

Methods: 40 rats were divided into normal group, model group, ShiZhiFang group, and benzbromarone group. The hyperuricemic rat model was induced by yeast gavage at 15 g/kg and potassium oxonate intraperitoneal injection at 600 mg/kg for two weeks. During the next two weeks, ShiZhiFang group rats were given ShiZhiFang by gavage, and benzbromarone group rats were given benzbromarone by gavage. The serum uric acid, creatinine, blood urea nitrogen, XOD activity, urinary uric acid, urinary -MG, and histopathological changes were observed in the rats of each group after treatment.

Results: The hyperuricemic model was established successfully and did not show the increase of serum creatinine and blood urea nitrogen. Compared with the model group, the serum uric acid, serum XOD activity, and urinary -MG were significantly decreased ( < 0.05), and 24 h urinary uric acid excretion was significantly decreased ( < 0.01) in ShiZhiFang group, whereas the two treatment groups were of no statistical significant in above indicators ( > 0.05); renal histopathology showed that the lesions in two treatment groups were reduced compared to the model groups. The gene and protein expression of uric acid anion transporters rOAT1 and rOAT3 in the kidney was significantly higher than that in model group ( < 0.01).

Conclusion: The model is suitable for the study of primary hyperuricemia. The mechanisms of ShiZhiFang on uric acid metabolism in hyperuricemic rats may be involved in reducing the activity of serum XOD and promoting the transcription and expression of rOAT1 and rOAT3 in the kidney.
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http://dx.doi.org/10.1155/2018/6821387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036841PMC
June 2018

Enhancing robustness of interdependent network under recovery based on a two-layer-protection strategy.

Sci Rep 2017 10 6;7(1):12753. Epub 2017 Oct 6.

Key Lab of Intelligent Perception and Image Understanding of Ministry of Education, International Research Center for Intelligent Perception and Computation, Xidian University, Xi'an, Shaanxi Province, 710071, China.

The robustness of coupled networks has attracted great attention recently, because the spread of failures from one network to its coupled network makes the coupled networks more vulnerable. Most existing achievements mainly focused on the integrity properties of coupled networks. However, failures also exist when networks are being reconstructed. Moreover, existing node-protection methods which aim to enhance the robustness of coupled networks only protect the influential nodes in one layer. In this paper, firstly, a two-layer-protection strategy is proposed to enhance the robustness of coupled networks under their reconstruction. Secondly, we adopt five strategies based on different centralities to select influential nodes, and propose a two-layer vision for each of them. Lastly, experiments on three different coupled networks show that by applying the two-layer-protection strategy, the robustness of coupled networks can be enhanced more efficiently compared with other methods which only protect nodes in one layer.
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http://dx.doi.org/10.1038/s41598-017-13063-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630635PMC
October 2017

Meta-analysis of expression and function of neprilysin in Alzheimer's disease.

Neurosci Lett 2017 Sep 2;657:69-76. Epub 2017 Aug 2.

Department of Occupational and Environmental Health Sciences, Peking University, Beijing, 100191, China. Electronic address:

Neprilysin (NEP) is one of the most important Aβ-degrading enzymes, and its expression and activity in Alzheimer's brain have been widely reported, but the results remain debatable. Thus, the meta-analysis was performed to elucidate the role of NEP in Alzheimer's disease (AD). The relevant case-control or cohort studies were retrieved according to our inclusion/exclusion criteria. Six studies with 123 controls and 141 AD cases, seven studies with 102 controls and 90 AD cases, and four studies with 93 controls and 132 AD cases were included in meta-analysis of NEP's protein, mRNA, and enzyme activity respectively. We conducted Meta regression to detect the sources of heterogeneity and further performed cumulative meta-analysis or subgroup analysis. Our meta-analysis revealed a significantly lower level of NEP mRNA (SMD=-0.44, 95%CI: -0.87, -0.00, p=0.049) in AD cases than in non-AD cases, and such pattern was not altered over time in the cumulative meta-analysis. However, the decrease of NEP protein (SMD=-0.18, 95%CI: -0.62, 0.25) and enzyme activity (SMD=-0.35, 95%CI: -1.03, 0.32) in AD cases did not pass the significance check, while the cumulative meta-analysis by average age showed the pooled effect became insignificant as adding the studies with younger subjects, which indicates that the protein expression and enzyme activity of NEP in the cortex are affected by age. Therefore, the present meta-analysis suggests the need of further investigation of roles of NEP in AD pathogenesis and treatment.
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http://dx.doi.org/10.1016/j.neulet.2017.07.060DOI Listing
September 2017

A Study of Cell-free DNA Fragmentation Pattern and Its Application in DNA Sample Type Classification.

IEEE/ACM Trans Comput Biol Bioinform 2017 Jul 4. Epub 2017 Jul 4.

Plasma cell-free DNA (cfDNA) has certain fragmentation patterns, which can bring non-random base content curves of the sequencing data's beginning cycles. We studied the patterns and found that we could determine whether a sample is cfDNA or not by just looking into the first 10 cycles of its base content curves. We analysed 3189 FastQ files, including 1442 cfDNA, 1234 genomic DNA, 507 FFPE tumour DNA and 6 urinary cfDNA. By deep analysing these data, we find the patterns are stable enough to distinguish cfDNA from other kinds of DNA samples. Based on this finding, we build classification models to recognise cfDNA samples by their sequencing data. Pattern recognition models are then trained with different classification algorithms like k-nearest neighbours (KNN), random forest and support vector machine (SVM). The result of 1000 iteration .632+ bootstrapping shows that all these classifiers can give an average accuracy higher than 98%, indicating that the cfDNA patterns are unique and can make the dataset highly separable. The best result is obtained using random forest classifier with a 99.89% average accuracy (σ = 0.00068). A tool called CfdnaPattern (http://github.com/OpenGene/CfdnaPattern) has been developed to train the model and to predict whether a sample is cfDNA or not.
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http://dx.doi.org/10.1109/TCBB.2017.2723388DOI Listing
July 2017

Contributions of molecular size, charge distribution, and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum hydrolysates.

Food Chem 2017 Sep 14;230:627-636. Epub 2017 Mar 14.

School of Food Science and Technology, Dalian Polytechnic University, National Engineering Research Center of Seafood, Dalian 116034, PR China. Electronic address:

This study investigated the contributions of molecular size, charge distribution and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum hydrolysates (SCOHs), and further explored their iron-binding sites. It was demonstrated that enzyme type and degree of hydrolysis (DH) significantly influenced the iron-binding capacity of the SCOHs. The SCOHs produced by alcalase at a DH of 25.9% possessed the highest iron-binding capacity at 92.1%. As the hydrolysis time increased, the molecular size of the SCOHs decreased, the negative charges increased, and the hydrophilic amino acids were exposed to the surface, facilitating iron binding. Furthermore, the Fourier transform infrared spectra, combined with amino acid composition analysis, revealed that iron bound to the SCOHs primarily through interactions with carboxyl oxygen of Asp, guanidine nitrogen of Arg or nitrogen atoms in imidazole group of His. The formed SCOHs-iron complexes exhibited a fold and crystal structure with spherical particles.
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http://dx.doi.org/10.1016/j.foodchem.2017.03.077DOI Listing
September 2017

Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation.

Plant Physiol 2016 11 5;172(3):1862-1875. Epub 2016 Oct 5.

Department of Plant Biology, Ecology, and Evolution, Oklahoma State University, Stillwater, Oklahoma 74078

Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes.
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http://dx.doi.org/10.1104/pp.16.01291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100756PMC
November 2016
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