Publications by authors named "Fang Liu"

3,911 Publications

  • Page 1 of 1

Putting Density Functional Theory to the Test in Machine-Learning-Accelerated Materials Discovery.

J Phys Chem Lett 2021 May 11:4628-4637. Epub 2021 May 11.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Accelerated discovery with machine learning (ML) has begun to provide the advances in efficiency needed to overcome the combinatorial challenge of computational materials design. Nevertheless, ML-accelerated discovery both inherits the biases of training data derived from density functional theory (DFT) and leads to many attempted calculations that are doomed to fail. Many compelling functional materials and catalytic processes involve strained chemical bonds, open-shell radicals and diradicals, or metal-organic bonds to open-shell transition-metal centers. Although promising targets, these materials present unique challenges for electronic structure methods and combinatorial challenges for their discovery. In this Perspective, we describe the advances needed in accuracy, efficiency, and approach beyond what is typical in conventional DFT-based ML workflows. These challenges have begun to be addressed through ML models trained to predict the results of multiple methods or the differences between them, enabling quantitative sensitivity analysis. For DFT to be trusted for a given data point in a high-throughput screen, it must pass a series of tests. ML models that predict the likelihood of calculation success and detect the presence of strong correlation will enable rapid diagnoses and adaptation strategies. These "decision engines" represent the first steps toward autonomous workflows that avoid the need for expert determination of the robustness of DFT-based materials discoveries.
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http://dx.doi.org/10.1021/acs.jpclett.1c00631DOI Listing
May 2021

Comparative genome analyses highlight transposon-mediated genome expansion and the evolutionary architecture of 3D genomic folding in cotton.

Mol Biol Evol 2021 May 11. Epub 2021 May 11.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, Hubei, China.

Transposable element (TE) amplification has been recognized as a driving force mediating genome size expansion and evolution, but the consequences for shaping 3D genomic architecture remains largely unknown in plants. Here, we report reference-grade genome assemblies for three species of cotton ranging three-fold in genome size, namely Gossypium rotundifolium (K2), G. arboreum (A2), and G. raimondii (D5), using Oxford Nanopore Technologies. Comparative genome analyses document the details of lineage-specific TE amplification contributing to the large genome size differences (K2, 2.44 Gb; A2, 1.62 Gb; D5, 750.19 Mb), and indicate relatively conserved gene content and synteny relationships among genomes. We found that approximately 17% of syntenic genes exhibit chromatin status change between active ("A") and inactive ("B") compartments, and TE amplification was associated with the increase of the proportion of A compartment in gene regions (∼ 7,000 genes) in K2 and A2 relative to D5. Only 42% of topologically associating domain (TAD) boundaries were conserved among the three genomes. Our data implicate recent amplification of TEs following formation of lineage-specific TAD boundaries. This study sheds light on the role of transposon-mediated genome expansion in the evolution of higher-order chromatin structure in plants.
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http://dx.doi.org/10.1093/molbev/msab128DOI Listing
May 2021

Corrigendum to: "Transgenic Cry1Ac/CpTI cotton assessment finds no detrimental effects on the insect predator Chrysoperla sinica" [Ecotoxicol. Environ. Saf. 208 (2021) 111680].

Ecotoxicol Environ Saf 2021 May 8;218:112301. Epub 2021 May 8.

Zhengzhou Research Base, State Key Laboratory of Cotton Biology, School of Life Science, Zhengzhou University, Zhengzhou 450001, China; State Key Laboratory of Cotton Biology, Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang, Henan 455000, China. Electronic address:

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http://dx.doi.org/10.1016/j.ecoenv.2021.112301DOI Listing
May 2021

Microbial community and metabolic function analysis of cigar tobacco leaves during fermentation.

Microbiologyopen 2021 Feb;10(2):e1171

College of Tobacco Science, Henan Agricultural University, Zhengzhou, China.

Cigar tobacco leaves (CTLs) contain abundant bacteria and fungi that are vital to leaf quality during fermentation. In this study, artificial fermentation was used for the fermentation of CTLs since it was more controllable and efficient than natural aging. The bacterial and fungal community structure and composition in unfermented and fermented CTLs were determined to understand the effects of microbes on the characteristics of CTLs during artificial fermentation. The relationship between the chemical contents and alterations in the microbial composition was evaluated, and the functions of bacteria and fungi in fermented CTLs were predicted to determine the possible metabolic pathways. After artificial fermentation, the bacterial and fungal community structure significantly changed in CTLs. The total nitrate and nicotine contents were most readily affected by the bacterial and fungal communities, respectively. FAPROTAX software predictions of the bacterial community revealed increases in functions related to compound transformation after fermentation. FUNGuild predictions of the fungal community revealed an increase in the content of saprotrophic fungi after fermentation. These data provide information regarding the artificial fermentation mechanism of CTLs and will inform safety and quality improvements.
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http://dx.doi.org/10.1002/mbo3.1171DOI Listing
February 2021

Handgrip Strength-Related Factors Affecting Health Outcomes in Young Adults: Association with Cardiorespiratory Fitness.

Biomed Res Int 2021 21;2021:6645252. Epub 2021 Apr 21.

The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.

Objectives: Handgrip strength (HS) is a risk factor of all-cause mortality and cardiovascular diseases. However, the influencing factors and mechanisms contributing to this correlation remain unclear. Therefore, we aimed to explore factors related to HS and investigated the mechanism underlying its risk predictive value.

Methods: This was a prospective, cross-sectional study. One hundred forty-five participants were recruited from December 2019 to November 2020. HS was measured using a hydraulic hand dynamometer and adjusted for body mass index (HS) and body surface area (HS). Body composition was assessed via bioimpedance spectroscopy. Physical fitness was measured using a cardiopulmonary exercise test system. Univariate, multiple linear regression analyses and receiver operator characteristic curve (ROC) were conducted to evaluate the associations between various participant characteristics and HS.

Results: The average participant age was 21.68 ± 2.61 years (42.8% were male). We found positive correlations between HS/HS and VO, VE, Load, and MET in both sexes ( < 0.05). Lean-tissue, protein, total water, and inorganic salt percentages were positively correlated, and fat percentage was negatively correlated with HS in men and with HS and HS in women ( < 0.05). Multiple regression revealed that VO was independently associated with HS in both sexes ( = 0.215, 0.173; 95%confidence interval [CI] = 0.032 - 0.398, 0.026-0.321; = 0.022, 0.022, respectively) and independently associated with HS in women ( = 0.016, 95%CI = 0.004 - 0.029, = 0.011). ROC analysis showed that HS and HS can moderately identify normal VO in men (area under curve [AUC] = 0.754, 0.769; = 0.002, 0.001, respectively) and marginally identify normal VO in women (AUC = 0.643, 0.635; = 0.029, 0.042, respectively).

Conclusions: BMI- and BSA-adjusted HS could serve as indicators of physical health, and HS may moderately reflect cardiorespiratory fitness levels in healthy young adults, particularly in males. Clinical trials registry site and number: China Clinical Trial Center (ChiCTR1900028228).
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http://dx.doi.org/10.1155/2021/6645252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084643PMC
April 2021

Alteration of Gut Microbiome and Correlated Lipid Metabolism in Post-Stroke Depression.

Front Cell Infect Microbiol 2021 22;11:663967. Epub 2021 Apr 22.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The pathogenesis of post-stroke depression (PSD) remains largely unknown. There is growing evidence indicating that gut microbiota participates in the development of brain diseases through the gut-brain axis. Here, we aim to determine whether and how microbial composition and function altered among control, stroke and PSD rats.

Materials And Methods: After the PSD rat model was successfully established, gut microbiome combined with fecal metabolome approach were performed to identify potentially PSD-related gut microbes and their functional metabolites. Then, correlations between behavior indices and altered gut microbes, as well as correlations between altered gut microbial operational taxonomic units (OTUs) with differential metabolites in PSD rats were explored. Enrichment analysis was also conducted to uncover the crucial metabolic pathways related to PSD.

Results: Although there were some alterations in the microbiome and metabolism of the control and stroke rats, we found that the microbial and metabolic phenotypes of PSD rats were significantly different. The microbial composition of PSD showed a decreased species richness indices, characterized by 22 depleted OTUs mainly belonging to phylum , genus and . In addition, PSD was associated with disturbances of fecal metabolomics, among them Glutamate, Maleic acid, 5-Methyluridine, Gallocatechin, 1,5-Anhydroglucitol, L-Kynurenine, Daidzein, Cyanoalanine, Acetyl Alanine and 5-Methoxytryptamine were significantly related to disturbed gut microbiome (P ≤ 0.01). Disordered fecal metabolomics in PSD rats mainly assigned to lipid, amino acid, carbohydrate and nucleotide metabolism. The steroid biosynthesis was particularly enriched in PSD.

Conclusions: Our findings suggest that gut microbiome may participate in the development of PSD, the mechanism may be related to the regulation of lipid metabolism.
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http://dx.doi.org/10.3389/fcimb.2021.663967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100602PMC
April 2021

Preparation of FA-targeted magnetic nanocomposites co-loading TFPI-2 plasmid and cis-platinum and its targeted therapy effects on nasopharyngeal carcinoma.

Int J Med Sci 2021 9;18(11):2355-2365. Epub 2021 Apr 9.

Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.

The majority of patients diagnosed with nasopharyngeal carcinoma (NPC) present with advanced-stage disease. The main treatment for these patients is concurrent chemoradiotherapy, which has various side effects. To improve the therapeutic effects and reduce the side effects of NPC chemoradiotherapy, we constructed a multifunctional folic acid (FA)-targeted magnetic nanocomposite codelivering tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP). This novel nanocomposite (FA-MNP/CDDP/TFPI-2) was obtained by amidation and electrostatic adsorption between FA-methoxypolyethylene glycol-polyethyleneimine (FA-MPEG-PEI) containing the TFPI-2 plasmid and magnetic nanoparticles modified by aldehyde sodium alginate loaded with CDDP. Transmission electron microscopy (TEM) images showed that the size of the individual magnetite particle core was approximately 11.5 nm. The structure and composition of the nanocomposites were identified and examined by H nuclear magnetic resonance (NMR) spectroscopy and ultraviolet (UV) spectrophotometry. The fluorescence analysis, Prussian blue iron staining, magnetic resonance (MR) imaging and whole-body fluorescence imaging results demonstrated that FA-MNP/CDDP/TFPI-2 showed high gene transfection efficiency and could target tumor cells via folate receptor (FR)-mediated delivery. The codelivery analysis showed that the obtained FA-MNP/CDDP/TFPI-2 composite could cause significantly more apoptosis than treatment with CDDP or TFPI-2 alone. The results showed that the FA-MNP/CDDP/TFPI-2 composites were successfully synthesized and indicated to be a specific molecular target for the FR with significant inhibitory effects on the growth of HNE-1 cells.
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http://dx.doi.org/10.7150/ijms.52643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100641PMC
April 2021

Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma.

Life Sci 2021 May 6:119590. Epub 2021 May 6.

Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, China. Electronic address:

Aims: The expression of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 were found to be downregulated in glioma by RNA sequencing; however, the function and mechanism of both two genes in the development of glioma have not been studied.

Materials And Methods: QRT-PCR and western blot were used to determine the transcriptional and translational levels of moleculars. MSP and BSP assays were used to evaluate the methylation status of promoter CpG island. MTT, EdU, flow cytometry, and transwell assays were used to reveal biological effects. The in vivo mice model was used to validate the role of target genes in tumorigenesis.

Key Findings: The mRNA and protein expression of STXBP5 was significantly downregulated in glioma tissues and positively correlated with prognosis. STXBP5-AS1 was downregulated in glioma cells and tissues, and associated with tumor size and clinical stages. Both of two genes were significantly restored in cells treatment with 5-Aza. The promoter CpG island of STXBP5/STXBP5-AS1 was hypermethylated in glioma cells, but partially methylated in NHA cells. We found that promoter methylation frequency was significantly higher in glioma tissues. Functionally, overexpression of STXBP5 and STXBP5-AS1 inhibited cell proliferation, migration, and invasion and promoted apoptosis in vitro, whereas depletion of STXBP5 and STXBP5-AS1 showed opposite effects. Both the mRNA and protein expression of STXBP5 were positively regulated by STXBP5-AS1. Ectopic expression of STXBP5 and STXBP5-AS1 suppressed tumor formation in vivo.

Significance: Our findings suggested that epigenetically silenced STXBP5-AS1 and STXBP5 might act as novel tumor suppressors of glioma.
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http://dx.doi.org/10.1016/j.lfs.2021.119590DOI Listing
May 2021

Outcomes of Prosthesis-Patient Mismatch Following Supra-Annular Transcatheter Aortic Valve Replacement: From the STS/ACC TVT Registry.

JACC Cardiovasc Interv 2021 May;14(9):964-976

Department of Cardiothoracic Surgery, Houston Methodist DeBakey Heart and Vascular Institute, Houston, Texas, USA.

Objectives: The aim of this study was to assess the outcomes of severe prosthesis-patient mismatch (PPM) in the TVT (Transcatheter Valve Therapy) Registry in patients undergoing supra-annular transcatheter aortic valve replacement (TAVR) for de novo stenosis or failed surgical bioprostheses (transcatheter aortic valve [TAV]-in-surgical aortic valve [SAV]).

Background: Severe PPM has been associated with adverse outcomes following TAVR, yet the clinical outcome of severe PPM after supra-annular TAVR is largely unknown.

Methods: Supra-annular TAVR was performed in patients enrolled in the TVT Registry with de novo stenosis (n = 42,174) or TAV-in-SAV (n = 5,446). Valve Academic Research Consortium-3 criteria were used to define severe PPM. The clinical impact of severe PPM on 1-year mortality and valve-related readmission was assessed using multivariate regression. A generalized linear mixed model was used to evaluate predictors of severe PPM.

Results: Severe PPM was found in 5.3% of patients undergoing de novo TAVR and 27.0% of patients undergoing TAV-in-SAV. The presence of severe PPM was not significantly associated with 1-year mortality or valve-related readmissions in both groups. Mean aortic gradients were higher in patients with severe PPM than in those without severe PPM at 1 month (9.7 ± 5.7 mm Hg vs. 7.3 ± 4.0 mm Hg; p < 0.001) and 1 year (10.2 ± 6.4 mm Hg vs. 8.0 ± 4.3 mm Hg; p < 0.001). Pre-procedural factors, including a <20-mm aortic annulus, were positive predictors of severe PPM in patients undergoing de novo TAVR (area under the curve = 0.795) and TAV-in-SAV (area under the curve = 0.764).

Conclusions: Severe PPM after supra-annular TAVR was not associated with increased 1-year mortality or valve-related readmissions. Longer-term follow-up is needed to determine if higher residual gradients in patients with severe PPM predict long-term outcomes. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528).
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http://dx.doi.org/10.1016/j.jcin.2021.03.040DOI Listing
May 2021

Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort.

Mol Genet Genomic Med 2021 May 5:e1689. Epub 2021 May 5.

Department of Medical Genetics, Capital Institute of Pediatrics, Beijing, China.

Objective: We determined the yield, genetic spectrum, and actual origin of de novo mutations (DNMs) for infantile spasms (ISs) in a Chinese cohort. The efficacy of levetiracetam (LEV) for STXBP1-related ISs was explored also.

Methods: Targeted sequencing of 153 epilepsy-related candidate genes was applied to 289 Chinese patients with undiagnosed ISs. Trio-based amplicon deep sequencing was used for all DNMs to distinguish somatic/mosaic mutations from germline ones.

Results: Total of 26 DNMs were identified from 289 recruited Chinese patients with undiagnosed ISs. Among them, 24 DNMs were interpreted as pathogenic mutations based on American College of Medical Genetics and Genomics guidelines, contributing to 8.3% (24/289) of diagnosis yield in the Chinese IS cohort. CDKL5 and STXBP1 are the top genes with recurrent DNMs, accounting for 3.1% (9/289) of yield. Further deep resequencing for the trio members showed that 22.7% (5/22) of DNMs are actually somatic in the proband or a parent. These somatic carriers presented milder seizure attacks than those with true germline DNMs. After treatment with LEV for half a year, three patients with DNM in STXBP1 showed improved clinical symptoms, including seizure-free and normal electroencephalogram, except for a patient with a second DNM in DIAPH3.

Significance: Our study confirmed the contribution and genetic spectrum of DNMs in Chinese IS patients. Somatic mutation account for a quarter of DNMs in IS cases. Treatment with LEV improved the prognosis of STXBP1-related ISs.
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http://dx.doi.org/10.1002/mgg3.1689DOI Listing
May 2021

A novel tailored immune gene pairs signature for overall survival prediction in lower-grade gliomas.

Transl Oncol 2021 May 1;14(7):101109. Epub 2021 May 1.

Department of Neurosurgery, The affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 68 Gehu Road, Changzhou, Jiangsu 213000, China. Electronic address:

Lower-grade gliomas (LGGs) have a good prognosis with a wide range of overall survival (OS) outcomes. An accurate prognostic system can better predict survival time. An RNA-Sequencing (RNA-seq) prognostic signature showed a better predictive power than clinical predictor models. A signature constructed using gene pairs can transcend changes from biological heterogeneity, technical biases, and different measurement platforms. RNA-seq coupled with corresponding clinical information were extracted from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Immune-related gene pairs (IRGPs) were used to establish a prognostic signature through univariate and multivariate Cox proportional hazards regression. Weighted gene co-expression network analysis (WGCNA) was used to evaluate module eigengenes correlating with immune cell infiltration and to construct gene co-expression networks. Samples in the training and testing cohorts were dichotomized into high- and low-risk groups. Risk score was identified as an independent predictor, and exhibited a closed relationship with prognosis. WGCNA presented a gene set that was positively correlated with age, WHO grade, isocitrate dehydrogenase (IDH) mutation status, 1p/19 codeletion, risk score, and immune cell infiltrations (CD4 T cells, B cells, dendritic cells, and macrophages). A nomogram comprising of age, WHO grade, 1p/19q codeletion, and three gene pairs (BIRC5|SSTR2, BMP2|TNFRSF12A, and NRG3|TGFB2) was established as a tool for predicting OS. The IPGPs signature, which is associated with immune cell infiltration, is a novel tailored tool for individual-level prediction.
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http://dx.doi.org/10.1016/j.tranon.2021.101109DOI Listing
May 2021

Id4 Suppresses the Growth and Invasion of Colorectal Cancer HCT116 Cells through CK18-Related Inhibition of AKT and EMT Signaling.

J Oncol 2021 14;2021:6660486. Epub 2021 Apr 14.

Laboratory of Immuno-Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350014, China.

Id4 is one of the inhibitors of DNA-binding proteins (Id) and involved in the pathogenesis of numerous cancers. The specific mechanism underlying the Id4-mediated regulation of proliferation, invasion, and metastasis of colorectal cancer (CRC) cells is still largely unclear. In the present study, results showed CRC cells had a lower baseline Id4 expression than normal intestinal epithelial NCM460 cells. In order to explore the role of Id4 in the tumorigenicity, CRC HCT116 cells with stable Id4 expression were used, and results showed Id4 overexpression arrested the cell cycle at the G0/G1 phase, inhibited the cell proliferation and the colony formation, as well as suppressed the migration and invasion. In the in vivo model, Id4 overexpression inhibited the tumor growth and metastasis in the nude mice. Furthermore, Id4 overexpression upregulated the expression of proteins associated with cell proliferation, inhibited the PI3K/AKT pathway, and suppressed epithelial-mesenchymal transition (EMT) of HCT116 cells. Moreover, Id4 significantly decreased cytokeratin 18 (CK18) expression, but CK18 overexpression in Id4 expressing HCT116-Id4 cells rescued the activation of AKT, p-AKT, MMP2, MMP7, and E-cadherin. Collectively, our study indicated Id4 may inhibit CRC growth and metastasis through inhibiting the PI3K/AKT pathway in a CK18-dependent manner and suppressing EMT. Id4 may become a target for the treatment of CRC.
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http://dx.doi.org/10.1155/2021/6660486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060092PMC
April 2021

Preterm Birth and Birth Weight and the Risk of Type 1 Diabetes in Chinese Children.

Front Endocrinol (Lausanne) 2021 14;12:603277. Epub 2021 Apr 14.

Department of Endocrinology, National Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Aims: Findings from previous studies about the association of preterm birth as well as birth weight with the risk of T1DM were still inconsistent. We aimed to further clarify these associations based on Chinese children and explore the role of gender therein.

Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in China from 2017 to 2019. Children aged between 3 and 18 years old with complete information were included in this analysis. Multiple Poisson regression models were used for evaluating the associations of birth weight as well as preterm birth with T1DM in children.

Results: Out of 181,786 children, 82 childhood T1DM cases were identified from questionnaire survey. Children with preterm birth (<37 weeks) had higher risk of type 1 diabetes (OR: 3.17, 95%CI: 1.76-5.71). Children born with high birth weight (≥4,000g) had no statistically significant risk of T1DM (OR:1.71, 95%CI: 0.90-3.22). However, children's gender might modify the effect of high birth weight on T1DM (girls: OR: 3.15, 95%CI: 1.33-7.47; boys: OR: 0.99, 95%CI: 0.38-2.55, for interaction=0.065). In addition, children with low birth weight were not associated with T1DM (OR: 0.70, 95%CI: 0.24-2.08). The findings from matched data had the similar trend.

Conclusions: In China mainland, preterm birth increased the risk of childhood T1DM, but high birth weight only affected girls. Therefore, early prevention of T1DM may start with prenatal care to avoid adverse birth outcomes and more attention should be paid to children with preterm birth and girls with high birth weight after birth.
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http://dx.doi.org/10.3389/fendo.2021.603277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079970PMC
April 2021

Ratiometric fluorescence detection of sulfide ions based on lanthanide coordination polymer using guanosine diphosphate as ligand.

Colloids Surf B Biointerfaces 2021 Apr 28;204:111796. Epub 2021 Apr 28.

Jiangxi Key Laboratory of Industrial Ceramics, College of Materials and Chemical Engineering, Pingxiang University, Pingxiang, 337055, China.

The efficiency of energy transfer from guanine nucleotide to terbium ion (Tb) is affected by the phosphate group significantly. Compared with the biomolecules 5'-GMP (guanosine monophosphate), guanosine diphosphate (GDP) exhibits better sensitize ability to Tb ions luminescence. Assisted with the carboxycoumarin ligand, we synthesized a more stable optical Coumarin@GDP-Tb polymer with the characteristic emission peaks located on 440 nm and 545 nm in this work. The Coumarin@GDP-Tb polymer is not only rich in metal binding sites, but also maintains a moderate ionic binding force, which helps metal ions to bind or leave it easily. Experiment result shows that Coumarin@GDP-Tb polymer has the appropriate binding force for Fe ions, which can be destroyed by sulfur ions (S) as the formation of FeS precipitation. Based on this, Coumarin@GDP-Tb was designed as the ratio fluorescence probe for sulfur ions detection, where the fluorescence at 545 nm can be selectively quenched by Fe ions, while that at 440 nm was unaffected, in the presence of S ions, the quenched fluorescence can be recovered remarkably. With the increasing S ions from 0.1-45 μM, the ratio of fluorescence intensity at 545 nm to 440 nm (F/F) is linear to S concentration, and the detection limit of S was calculated to be 0.073 μM. Contrast to those fluorescence probes with single wavelength emission, Coumarin@GDP-Tb displays a comparable sensitivity, the introduced self-adjust wavelength improved the detection accuracy efficiently. The above 98.1 % recovery rates of S ions in the actual water sample demonstrated the practicability of Coumarin@GDP-Tb fluorescence probe.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111796DOI Listing
April 2021

Perforator preservation technologies (PPT) based on a new neuro-interventional classification in endovascular treatment of perforator involving aneurysms (piANs).

Chin Neurosurg J 2021 May 2;7(1):26. Epub 2021 May 2.

New Era Stroke Care and Research Institute, PLA Rocket Force Characteristic Medical Center, 18 Xinjiekouwai Street, Beijing, 100088, China.

Background: Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification.

Methods: The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed.

Results: Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13-50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence.

Conclusions: Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.
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http://dx.doi.org/10.1186/s41016-021-00243-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088693PMC
May 2021

BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial-mesenchymal transition and angiogenesis.

Cancer Med 2021 May 1. Epub 2021 May 1.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Metastasis to regional lymph nodes or distal organs predicts the progression of the disease and poor prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies demonstrated that BTB and CNC homology 1 (BACH1) participates in various types of tumor metastasis. However, the function of BACH1 in ESCC was rarely reported. The present study demonstrated that BACH1 protein was overexpressed in ESCC tissues compared with paired esophageal epithelial tissues according to immunohistochemical staining (IHC). Higher levels of BACH1 mRNA were associated with decreased overall survival (OS) and shorter disease-free survival (DFS) of ESCC patients based on an analysis of The Cancer Genome Atlas (TCGA) datasets. BACH1 significantly enhanced the migration and invasion of ESCC in vitro. Mechanistically, BACH1 promoted the epithelial-mesenchymal transition (EMT) by directly activating the transcription of CDH2, SNAI2, and VIM, as determined by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). BACH1 overexpression significantly enhanced CDH2 promoter activity according to the results of a luciferase assay. The results of subsequent experiments indicated that BACH1 enhanced the growth of tumor xenografts. The density of CD31 blood vessels and the expression of vascular endothelial growth factor C (VEGFC) in tumor xenografts were significantly associated with BACH1 levels according to the results of IHC and immunofluorescence (IF) analyses performed in vivo. Moreover, ChIP-qPCR analysis demonstrated that the transcriptional activity of VEGFC was also upregulated by BACH1. Thus, BACH1 contributes to ESCC metastasis and tumorigenesis by partially facilitating the EMT and angiogenesis, and BACH1 may be a promising therapeutic target or molecular marker in ESCC.
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http://dx.doi.org/10.1002/cam4.3884DOI Listing
May 2021

Vagus Nerve Stimulation Protects Enterocyte Glycocalyx After Hemorrhagic Shock Via The Cholinergic Anti-Inflammatory Pathway.

Shock 2021 Apr 22. Epub 2021 Apr 22.

Department of Anesthesiology, General Hospital of Central Theater Command of PLA, Wuhan, China, 430070 The First School of Clinical Medicine, Southern Medical University, Guangzhou, China, 510006.

Introduction: Electrical vagal nerve stimulation is known to decrease gut permeability and alleviate gut injury caused by traumatic hemorrhagic shock. However, the specific mechanism of action remains unclear. Glycocalyx, located on the surface of the intestinal epithelium, is associated with the buildup of the intestinal barrier. Therefore, the goal of our study was to explore whether vagal nerve stimulation affects enterocyte glycocalyx, gut permeability, gut injury, and remote lung injury.

Methods: Male Sprague Dawley rats were anesthetized and their cervical nerves were exposed. The rats underwent traumatic hemorrhagic shock (with maintenance of mean arterial pressure of 30-35 mmHg for 60 min) with fluid resuscitation. Vagal nerve stimulation was added to two cohorts of animals before fluid resuscitation, and one of them was injected with methyllycaconitine to block the cholinergic anti-inflammatory pathway. Intestinal epithelial glycocalyx was detected using immunofluorescence. Intestinal permeability, the degree of gut and lung injury, and inflammation factors were also assessed.

Results: Vagal nerve stimulation alleviated the damage to the intestinal epithelial glycocalyx and decreased intestinal permeability by 43% compared with the shock/resuscitation phase (P < 0.05). Methyllycaconitine partly eliminated the effects of vagal nerve stimulation on the intestinal epithelial glycocalyx (P < 0.05). Vagal nerve stimulation protected against traumatic hemorrhagic shock/fluid resuscitation-induced gut and lung injury, and some inflammatory factor levels in the gut and lung tissue were downregulated after vagal nerve stimulation (P < 0.05).

Conclusions: Vagal nerve stimulation could relieve traumatic hemorrhagic shock/fluid resuscitation-induced intestinal epithelial glycocalyx damage via the cholinergic anti-inflammatory pathway.
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http://dx.doi.org/10.1097/SHK.0000000000001791DOI Listing
April 2021

together with turmeric extract and pomegranate peel extract alleviates obesity in high fat-fed C57BL/6J mice.

Food Funct 2021 Apr 29. Epub 2021 Apr 29.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266100, China.

Sargassum fusiforme, a nutritious edible brown alga, has been widely suggested to play an important role in the development of functional food because of its multiple biological activities. The aim of this study was to explore the anti-obesity effect of the combination of Sargassum fusiforme with extracts of fruit and vegetable by comparing the effects of Sargassum fusiforme (S), Sargassum fusiforme together with pomegranate peel extract (SP), Sargassum fusiforme together with turmeric extract (ST) and Sargassum fusiforme together with turmeric extract and pomegranate peel extract (C) on diet-induced obese C57BL/6J mice. Long-term consumption of a high-fat diet can lead to high levels of blood lipid, increase adipocyte size, and cause lipid metabolism dysfunction and gut microbiota dysbiosis. According to the results of the experiments, SP and ST were more effective in reducing lipid levels and fat accumulation than S; and, C exhibited the strongest efficacy compared with the other three supplements. ST and C also regulated adipocytokines and had significant effects on the gene expression of lipid metabolism. We also found that C alleviated the imbalance of intestinal flora caused by a high-fat diet to a certain extent. In conclusion, SP, ST and C have anti-obesity potentials, which can be used as alternative ingredients in the formula of functional food for obese people.
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http://dx.doi.org/10.1039/d0fo03044aDOI Listing
April 2021

Relationship between small dense low-density lipoprotein cholesterol with carotid plaque in Chinese individuals with abnormal carotid artery intima-media thickness.

BMC Cardiovasc Disord 2021 Apr 27;21(1):216. Epub 2021 Apr 27.

Health Management Centre, Kaifeng Central Hospital, Kaifeng, 475000, Henan, China.

Aim: To investigate the relationship of small dense low-density lipoprotein cholesterol (sdLDL-C) to carotid artery intima-media thickness (CA-IMT) and carotid plaque (CAP) in Chinese general population, and to evaluate whether sdLDL-C could be an independent risk factor for individuals with subclinical atherosclerosis.

Methods: A total of 729 subjects were randomly collected from consecutive individuals from April 2019 to April 2020 for an annual health checkup. CA-IMT > 1.0 mm was defined as abnormal IMT. Plaque stability was measured by ultrasound examination based on the property of the echo. And sdLDL-C levels were detected by LipoPrint system. Multivariate logistic regression analysis was performed to identify factors associated with CA-IMT and carotid plaque.

Results: The abnormal IMT group had significantly higher sdLDL-C levels than control group (p < 0.0001). And sdLDL-C levels were significantly positively correlated with IMT value (r = 0.1396, p = 0.0021) and presence of carotid plaque (r = 0.14, p = 0.002) in the subjects with abnormal IMT. In addition, subjects with higher levels of sdLDL-C (r = 0.11, p = 0.035) tended to have unstable CAP. After adjustment for age, gender and blood glucose, sdLDL-C level was an independent risk factor of the presence of CAP (OR = 1.59, 95% CI: 1.02-1.83, p = 0.034) in subjects with abnormal IMT.

Conclusion: SdLDL-C is an independent risk factor of the occurrence of CAP in the Chinese subjects with abnormal IMT. Our findings provide supporting evidence that sdLDL-C might be an alternative way to predict CVD in early stage.
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http://dx.doi.org/10.1186/s12872-021-02023-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080368PMC
April 2021

The influence of CYP2C19 polymorphisms on voriconazole trough concentrations: Systematic review and meta-analysis.

Mycoses 2021 Apr 25. Epub 2021 Apr 25.

Department of Pharmacy, Peking University People's Hospital, Beijing, China.

Background: Voriconazole primary metabolism is catalysed by CYP2C19. A large variability of trough concentrations in patients with invasive fungal infection treated with voriconazole has been observed in clinical practice. It remains controversial whether the CYP2C19 polymorphisms are responsible for voriconazole metabolism in the individual variation.

Objectives: The primary aim of this study was to assess the effect of CYP2C19 polymorphisms on voriconazole trough concentrations.

Methods: Following a systematic literature review, we performed a meta-analysis for mean differences (MD) of voriconazole trough concentrations (C ), voriconazole dosage adjusted trough concentrations (C /D) and for risk ratio (RR) of the proportion of patients in the target therapeutic range between pairwise comparisons of CYP2C19 phenotypes.

Results: Compared with normal metabolisers (NMs), intermediate metabolisers (IMs) (MD: 0.82, 95% CI: 0.57 to 1.07, I  = 44%, p < .00001) or poor metabolisers (PMs) (MD: 1.59, 95% CI: 1.14 to 2.05, I  = 46%, p < .00001) had significantly higher voriconazole C (μg·ml ), while rapid metabolisers (RMs) had significantly lower voriconazole C (MD: -0,87, 95% CI: -1.35 to -0.38, I  = 0%, p = .0004). In addition, IMs had significantly lower C than PMs (MD: -0.59, 95% CI: -0.97 to -0.20, I  = 22%, p = .003). Similarly, the C /D (μg·kg·ml ·mg ) was significantly higher in IMs (MD: 0.13, 95% CI: 0.05 to 0.22, I  = 0%, p = .002) and PMs (MD: 0.20, 95% CI: 0.07 to 0.34, I  = 0%, p = .003) than that in NMs, and also, IMs had significantly lower C /D than PMs (MD: -0.11, 95% CI: -0.14 to -0.08, I  = 0%, p < .00001). Furthermore, PMs had a significantly higher proportion of the target therapeutic range than NMs (RR: 1.34, 95% CI: 1.09 to 1.64, I  = 50%, p = .005).

Conclusions: Compared to NMs, IMs and PMs had higher voriconazole trough concentrations, especially in Asians, while RMs had lower voriconazole trough concentrations. In addition, PMs had a higher proportion of the target therapeutic range than NMs, especially in Asians. CYP2C19 genotyping is expected to be used to preemptively guide the individualisation of voriconazole in clinical practice.
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http://dx.doi.org/10.1111/myc.13293DOI Listing
April 2021

Effect of Robot Assisted Gait Training on Motor and Walking Function in Patients with Subacute Stroke: A Random Controlled Study.

J Stroke Cerebrovasc Dis 2021 Apr 22;30(7):105807. Epub 2021 Apr 22.

Department of Rehabilitation, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, China. Electronic address:

Background: Robot-assisted gait training has been confirmed to have beneficial effect on the rehabilitation of stroke patients. An exoskeleton robot, named BEAR-H1, is designed to help stroke patients with walking disabilities.

Methods: 17 subjects in experimental group and 15 subjects in control group completed the study. The experimental group received 30 minutes of BEAR-H1 assisted gait training(BAGT), and the control group received 30 minutes of conventional training, 5 times/week for 4weeks. All subjects were evaluated with 6-minute walk test (6MWT), Fugl-Meyer Assessment for lower extremity (FMA-LE), Functional Ambulatory Classification (FAC), Modified Ashworth Scale (MAS), and gait analysis at baseline and after 4 weeks intervention.

Results: The improvements of 6MWT, FMA-LE, gait speed, cadence, step length and cycle duration in BAGT group were more noticeable than in the control group. However, there was no difference in the assessment of MAS between two groups.

Conclusions: Our results showed that BAGT is an effective intervention to improve the motor and walking ability during 4 weeks training for subacute stroke patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105807DOI Listing
April 2021

Zika virus dysregulates the expression of astrocytic genes involved in neurodevelopment.

PLoS Negl Trop Dis 2021 Apr 23;15(4):e0009362. Epub 2021 Apr 23.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead to dysregulation of numerous functions including neurons development and migration, glial cells differentiation, myelinations, astrocytes projection, neurogenesis, and brain development, along with multiple pathways including Hippo signaling pathway, tight junction, PI3K-Akt signaling pathway, and focal adhesion. Furthermore, we confirmed the dysregulation of the selected genes in MPAs and human astroglioma U251 cells. We found that PTBP1, LIF, GHR, and PTBP3 were upregulated while EDNRB and MBP were downregulated upon ZIKV infection. The current study highlights the ZIKV-mediated potential genes associated with neurodevelopment or related diseases.
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http://dx.doi.org/10.1371/journal.pntd.0009362DOI Listing
April 2021

Noncontrast Magnetic Resonance Radiomics and Multilayer Perceptron Network Classifier: An approach for Predicting Fibroblast Activation Protein Expression in Patients With Pancreatic Ductal Adenocarcinoma.

J Magn Reson Imaging 2021 Apr 22. Epub 2021 Apr 22.

Department of Radiology, Changhai Hospital, Navy Medical University, Shanghai, China.

Background: Fibroblast activation protein (FAP) in pancreatic ductal adenocarcinoma (PDAC) is closely related to the prognosis and treatment of patients. Accurate preoperative FAP expression can better identify the population benefitting from FAP-targeting drugs.

Purpose: To develop and validate a machine learning classifier based on noncontrast MRI for the preoperative prediction of FAP expression in patients with PDAC.

Study Type: Retrospective cohort study.

Population: Altogether, 129 patients with pathology-confirmed PDAC undergoing MR scan and surgical resection; 90 patients in a training cohort, and 39 patients in a validation cohort. FIELD STRENGTH/SEQUENCE/3T: Breath-hold single-shot fast-spin echo T2-weighted sequence and unenhanced and noncontrast T1-weighted fat-suppressed sequences.

Assessment: FAP expression was quantified using immunohistochemistry. For each patient, 1409 radiomics features were extracted from T1- and T2-weighted images and reduced using the least absolute shrinkage and selection operator logistic regression algorithm. A multilayer perceptron (MLP) network classifier was developed using the training and validation set. The MLP network classifier performance was determined by its discriminative ability, calibration, and clinical utility.

Statistical Tests: Kaplan-Meier estimates, student's t-test, the Kruskal-Wallis H test, and the chi-square test, univariable regression analysis, receiver operating characteristic curve, and decision curve analysis were used.

Results: A log-rank test showed that the survival of patients with low FAP expression (24.43 months) was significantly longer (P < 0.05) than that in the FAP-high group (13.50 months). The prediction model showed good discrimination in the training set (area under the curve [AUC], 0.84) and the validation set (AUC, 0.77). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the training set were 75.00%, 79.41%, 0.77, 0.86, and 0.66, respectively, whereas those for the validation set were 85.00%, 63.16%, 0.74, 0.71, and 0.80, respectively.

Data Conclusions: The MLP network classifier based on noncontrast MRI can accurately predict FAP expression in patients with PDAC.

Evidence Level: 2 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27648DOI Listing
April 2021

Transcriptome integration analysis and specific diagnosis model construction for Hodgkin's lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma.

Aging (Albany NY) 2021 Apr 22;13(8):11833-11859. Epub 2021 Apr 22.

Foshan Stomatology Hospital, School of Medicine, Foshan University, Foshan, Guangdong, China.

Transcriptome differences between Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL), which are all derived from B cell, remained unclear. This study aimed to construct lymphoma-specific diagnostic models by screening lymphoma marker genes. Transcriptome data of HL, DLBCL, and MCL were obtained from public databases. Lymphoma marker genes were screened by comparing cases and controls as well as the intergroup differences among lymphomas. A total of 9 HL marker genes, 7 DLBCL marker genes, and 4 MCL marker genes were screened in this study. Most HL marker genes were upregulated, whereas DLBCL and MCL marker genes were downregulated compared to controls. The optimal HL-specific diagnostic model contains one marker gene (MYH2) with an AUC of 0.901. The optimal DLBCL-specific diagnostic model contains 7 marker genes (LIPF, CCDC144B, PRO2964, PHF1, SFTPA2, NTS, and HP) with an AUC of 0.951. The optimal MCL-specific diagnostic model contains 3 marker genes (IGLV3-19, IGKV4-1, and PRB3) with an AUC of 0.843. The present study reveals the transcriptome data-based differences between HL, DLBCL, and MCL, when combined with other clinical markers, may help the clinical diagnosis and prognosis.
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http://dx.doi.org/10.18632/aging.202882DOI Listing
April 2021

Fibrous Dysplasia Mimicking Skeletal Metastasis on 68Ga-FAPI PET Imaging.

Clin Nucl Med 2021 Apr 20. Epub 2021 Apr 20.

From the Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; and Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.

Abstract: 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET imaging has been introduced for detecting many primary and metastatic tumors. However, false-positive uptakes have been reported in some benign lesions. Here, we presented a 68Ga-FAPI-avid lesion in the left temporal bone in a 41-year-old man with a history of signet ring cell gastric adenocarcinoma. The osseous lesion was finally distinguished as fibrous dysplasia according to the clinical and imaging findings. This case suggests that 68Ga-FAPI may have false-positive uptakes in bone benign lesions, which should be paid attention to in the diagnosis of bone lesions in patients with malignant tumors.
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http://dx.doi.org/10.1097/RLU.0000000000003671DOI Listing
April 2021

Type of Architecture, Presence of Punctate Necrosis, and Extent of Involvement in Atypical Ductal Hyperplasia Can Predict the Diagnosis of Breast Carcinoma on Excision: A Clinicopathologic Study of 143 Cases.

Int J Surg Pathol 2021 Apr 21:10668969211010954. Epub 2021 Apr 21.

22209Women & Infants Hospital of Rhode Island, Providence, RI, USA.

The literature shows a wide range in the frequencies of finding breast carcinoma in the excised specimens following a biopsy diagnosis of atypical ductal hyperplasia (ADH), likely due to a poor diagnostic reproducibility among different pathologists as well as an inherent heterogeneity in ADH. We evaluated whether histologic subtyping of ADH would help predict the risk of breast carcinoma. Our study consisted of 143 cases of ADH diagnosed by core needle biopsy and followed by excision. Of these, 54 cases (37.8%) showed carcinoma in the excised specimens (47 cases of ductal carcinoma in situ alone, 3 cases of invasive ductal carcinoma alone, and 4 cases of mixed invasive ductal carcinoma and ductal carcinoma in situ). We arbitrarily divided ADH into two subtypes: type A was considered when one or more ducts were completely replaced by low-grade ductal carcinoma in situ type cells but the lesion was <2 mm and type B was considered when one or more ducts were partially involved by low-grade ductal carcinoma in situ type cells regardless of lesion size. Type A was associated with a significantly higher frequency of breast carcinoma (63.6%) than type B (30.0%). ADH containing punctate necrosis showed a higher association of carcinoma (66.7%) compared to those without necrosis (35.1%). Within type B ADH, involvement of 3 or more foci had a higher frequency of carcinoma (50.0%) than involvement of fewer foci (26.6%). These histologic features of ADH may prove useful in predicting the likelihood of breast carcinoma and provide helpful information for patient's management.
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http://dx.doi.org/10.1177/10668969211010954DOI Listing
April 2021

On the use of GBLUP and its extension for GWAS with additive and epistatic effects.

G3 (Bethesda) 2021 Apr 19. Epub 2021 Apr 19.

Department of Breeding Research, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben, 06466 Stadt Seeland, Germany.

Genomic best linear unbiased prediction (GBLUP) is the most widely used model for genome-wide predictions. Interestingly, it is also possible to perform genome-wide association studies (GWAS) based on GBLUP. Although the estimated marker effects in GBLUP are shrunken and the conventional test based on such effects has low power, it was observed that a modified test statistic can be produced and the result of test was identical to a standard GWAS model. Later, a mathematical proof was given for the special case that there is no fixed covariate in GBLUP. Since then, the new approach has been called "GWAS by GBLUP". Nevertheless, covariates such as environmental and subpopulation effects are very common in GBLUP. Thus, it is necessary to confirm the equivalence in the general case. Recently, the concept was generalized to GWAS for epistatic effects and the new approach was termed rapid epistatic mixed-model association analysis (REMMA) because it greatly improved the computational efficiency. However, the relationship between REMMA and the standard GWAS model has not been investigated. In this study, we first provided a general mathematical proof of the equivalence between" GWAS by GBLUP" and the standard GWAS model for additive effects. Then, we compared REMMA with the standard GWAS model for epistatic effects by a theoretical investigation and by empirical data analyses. We hypothesized that the similarity of the two models is influenced by the relative contribution of additive and epistatic effects to the phenotypic variance, which was verified by empirical and simulation studies.
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http://dx.doi.org/10.1093/g3journal/jkab122DOI Listing
April 2021

Ga-DOTA-FAPI-04 PET/MR in the evaluation of gastric carcinomas: comparison with F-FDG PET/CT.

J Nucl Med 2021 Apr 16. Epub 2021 Apr 16.

Union Hospital, Tongji Medical College, Huazhong University of Science & Technology.

We sought to evaluate the performance of Ga-DOTA-FAPI-04 (Ga-FAPI) PET/MR for the diagnosis of primary tumor and metastatic lesions in patients with gastric carcinomas and to compare the results with those of F-FDG PET/CT. Twenty patients with histologically proven gastric carcinomas were recruited, and each patient underwent both F-FDG PET/CT and Ga-FAPI PET/MR. A visual scoring system was established to compare the detectability of primary tumors and metastases in different organs/regions (the peritoneum, abdominal lymph nodes, supradiaphragmatic lymph nodes, liver, ovary, bone, and other tissues). The original maximum standardized uptake value (SUV) and normalized SUV (calculated by dividing a lesion's original SUV with the mean SUV of the descending aorta) of selected lesions on both F-FDG PET/CT and Ga-FAPI PET/MR were measured. Original/normalized SUV-FAPI and SUV-FDG were compared for patient-based (including a single lesion with the highest activity uptake in each organ/region) and lesion-based (including all lesions [≤ 5] or the 5 lesions with highest activity [> 5]) analyses, respectively. The 20 recruited patients (median age: 56.0 y; range: 29-70 y) included 9 men and 11 women, 14 patients for initial staging and 6 for recurrence detection. Ga-FAPI PET was superior to F-FDG PET for primary tumor detection (100.00% [14/14] vs 71.43% [10/14], = 0.034), and the former had higher tracer uptake levels ( < 0.05). Ga-FAPI PET was superior to F-FDG PET in both patient-based and lesion-based evaluation except for the metastatic lesions in supradiaphragmatic lymph nodes and ovaries. Additionally, multiple sequences of MR images were beneficial for the interpretation of hepatic metastases in 3 patients, uterine and rectal metastases in 1 patient, ovarian lesions in 7 patients, and osseous metastases in 2 patients. Ga-FAPI PET/MR outperformed F-FDG PET/CT in visualizing the primary and most metastatic lesions of gastric cancer, and might be a promising method with the potential of replacing F-FDG PET/CT.
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http://dx.doi.org/10.2967/jnumed.120.258467DOI Listing
April 2021

Automatic Detection of Obstructive Sleep Apnea Events Using a Deep CNN-LSTM Model.

Comput Intell Neurosci 2021 22;2021:5594733. Epub 2021 Mar 22.

College of Information Engineering, Huanghuai University, Zhumadian, Henan 463000, China.

Obstructive sleep apnea (OSA) is a common sleep-related respiratory disorder. Around the world, more and more people are suffering from OSA. Because of the limitation of monitor equipment, many people with OSA remain undetected. Therefore, we propose a sleep-monitoring model based on single-channel electrocardiogram using a convolutional neural network (CNN), which can be used in portable OSA monitor devices. To learn different scale features, the first convolution layer comprises three types of filters. The long short-term memory (LSTM) is used to learn the long-term dependencies such as the OSA transition rules. The softmax function is connected to the final fully connected layer to obtain the final decision. To detect a complete OSA event, the raw ECG signals are segmented by a 10 s overlapping sliding window. The proposed model is trained with the segmented raw signals and is subsequently tested to evaluate its event detection performance. According to experiment analysis, the proposed model exhibits Cohen's kappa coefficient of 0.92, a sensitivity of 96.1%, a specificity of 96.2%, and an accuracy of 96.1% with respect to the Apnea-ECG dataset. The proposed model is significantly higher than the results from the baseline method. The results prove that our approach could be a useful tool for detecting OSA on the basis of a single-lead ECG.
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http://dx.doi.org/10.1155/2021/5594733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009718PMC
March 2021

Association between cigarette smoking and colorectal cancer sidedness: A multi-center big-data platform-based analysis.

J Transl Med 2021 04 15;19(1):150. Epub 2021 Apr 15.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.

Background: Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis.

Methods: In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC.

Results: History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 - 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC.

Conclusions: History of smoking was associated with LSCRC in a positive dose-response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.
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http://dx.doi.org/10.1186/s12967-021-02815-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048178PMC
April 2021