Publications by authors named "Chenyang Wang"

172 Publications

Associations between Fast-Food Restaurants Surrounding Kindergartens and Childhood Obesity: Evidence from China.

Int J Environ Res Public Health 2021 Sep 3;18(17). Epub 2021 Sep 3.

Theoretical Teaching and Research Section, College of Physical Education and Sports, Beijing Normal University, Beijing 100875, China.

The prevalence of obesity among preschool children has risen dramatically due to the influx of Western fast food in China. In this study, we aimed to provide clear evidence on the associations between fast-food restaurants and childhood obesity. We collected and combined three unique cross-sectional datasets: physical fitness data, geographic information, and the financial data of each kindergarten. The two-stage least squares were used for empirical analyses. The final data including 75,730 children were from 785 kindergartens in 82 cities and 23 provinces in China in 2018. The mean age of participants was 4.94 ± 0.87; 34,249 (45.2%) females and 41,481 (54.8%) males. The number of fast-food restaurants within 1, 2, and 3 km radii had a significant and positive correlation with obesity, and this correlation decreased as the radius increased. Furthermore, the distance to the nearest fast-food restaurant had a significant and negative correlation with obesity. Western fast-food restaurants contributed more to obesity than the broader definition of fast-food restaurants. There was marked heterogeneity between urban and rural areas. Our findings documented that fast-food restaurants had a significant and positive association with childhood obesity, thus the restriction of fast-food restaurants surrounding kindergartens might be considered.
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http://dx.doi.org/10.3390/ijerph18179334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431518PMC
September 2021

Visible light-induced C-C bond cleavage in a multicomponent reaction cascade allowing acylations of sulfoximines with ketones.

Org Biomol Chem 2021 Sep 6. Epub 2021 Sep 6.

Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.

Visible light induces C-C-bond cleavage reactions of ketones, which can be utilized for -acylations of sulfoximines. No (photo)catalyst is required, and the reactions occur at ambient temperature in air. The substrate scope is broad for both ketones and sulfoximines. For converting H-sulfoximines, the presence of NBS is essential.
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http://dx.doi.org/10.1039/d1ob01411kDOI Listing
September 2021

Comparative Study of Government Response Measures and Epidemic Trends for COVID-19 Global Pandemic.

Risk Anal 2021 Sep 5. Epub 2021 Sep 5.

Department of Engineering Physics, Tsinghua University, Beijing, China.

The ongoing novel coronavirus (COVID-19) epidemic has evolved into a full range of challenges that the world is facing. Health and economic threats caused governments to take preventive measures against the spread of the disease. This study aims to provide a correlation analysis of the response measures adopted by countries and epidemic trends since the COVID-19 outbreak. This analysis picks 13 countries for quantitative assessment. We select a trusted model to fit the epidemic trend curves in segments and catch the characteristics based on which we explore the key factors of COVID-19 spread. This review generates a score table of government response measures according to the Likert scale. We use the Delphi method to obtain expert judgments about the government response in the Likert scale. Furthermore, we find a significant negative correlation between the epidemic trend characteristics and the government response measure scores given by experts through correlation analysis. More stringent government response measures correlate with fewer infections and fewer waves in the infection curves. Stringent government response measures curb the spread of COVID-19, limit the number of total infectious cases, and reduce the time to peak of total cases. The clusters of the results categorize the countries into two specific groups. This study will improve our understanding of the prevention of COVID-19 spread and government response.
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http://dx.doi.org/10.1111/risa.13817DOI Listing
September 2021

Photocatalytic Synthesis of Difluoroacetoxy-containing Sulfoximines.

Org Lett 2021 Sep 20;23(17):6891-6894. Epub 2021 Aug 20.

Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany.

[Bis(difluoroacetoxy)iodo]benzene and H-sulfoximines react to give new hypervalent iodine(III) reagents, which under photocatalysis transfer difluoroacetoxy and sulfoximidoyl groups to styrenes with high regioselectivity. The results of mechanistic investigations suggest the intermediacy of radicals and reveal the importance of the difluoroacetoxy group on the iodine reagent.
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http://dx.doi.org/10.1021/acs.orglett.1c02452DOI Listing
September 2021

An end-to-end heterogeneous graph attention network for Mycobacterium tuberculosis drug-resistance prediction.

Brief Bioinform 2021 Aug 20. Epub 2021 Aug 20.

Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, OX3 7DQ, UK.

Antimicrobial resistance (AMR) poses a threat to global public health. To mitigate the impacts of AMR, it is important to identify the molecular mechanisms of AMR and thereby determine optimal therapy as early as possible. Conventional machine learning-based drug-resistance analyses assume genetic variations to be homogeneous, thus not distinguishing between coding and intergenic sequences. In this study, we represent genetic data from Mycobacterium tuberculosis as a graph, and then adopt a deep graph learning method-heterogeneous graph attention network ('HGAT-AMR')-to predict anti-tuberculosis (TB) drug resistance. The HGAT-AMR model is able to accommodate incomplete phenotypic profiles, as well as provide 'attention scores' of genes and single nucleotide polymorphisms (SNPs) both at a population level and for individual samples. These scores encode the inputs, which the model is 'paying attention to' in making its drug resistance predictions. The results show that the proposed model generated the best area under the receiver operating characteristic (AUROC) for isoniazid and rifampicin (98.53 and 99.10%), the best sensitivity for three first-line drugs (94.91% for isoniazid, 96.60% for ethambutol and 90.63% for pyrazinamide), and maintained performance when the data were associated with incomplete phenotypes (i.e. for those isolates for which phenotypic data for some drugs were missing). We also demonstrate that the model successfully identifies genes and SNPs associated with drug resistance, mitigating the impact of resistance profile while considering particular drug resistance, which is consistent with domain knowledge.
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http://dx.doi.org/10.1093/bib/bbab299DOI Listing
August 2021

Sandwich optoplasmonic hybrid structure for surface enhanced Raman spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 6;264:120252. Epub 2021 Aug 6.

Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China. Electronic address:

Combined with photonic microstructure and plasmonic nanostructure, the optoplasmonic hybrid structure with fantastic optical properties attracts lots of attentions in recent years. With the help of light enrichment by dielectric photonic microenvironment, the embedded plasmonic nanoantennas generate much greater electromagnetic field enhancement at surface for light harvesting compared to conventional plasmonic nanostructures. In this work, a sandwich optoplasmonic hybrid structure is developed for surface enhanced Raman spectroscopy (SERS) detection, which is consisted of polymethyl methacrylate (PMMA) microspheres array, self-assembled Ag nanoparticles (AgNPs) film and SiO microsphere ([email protected]@SiO). The SERS spectra collected on this optoplasmonic substrate point out it has high sensitivity with limit of detection (LOD) at 10 fM. The experimental data demonstrate both the PMMA microarray and SiO microsphere play important roles in enrichment of light illuminating at AgNPs for SERS detection, which is confirmed by the simulated electric field distributions. This sandwich optoplasmonic hybrid structure not only enlarges research field of surface plasmon, but also provides a novel SERS subtract for sensitive analysis in chem/bio-field.
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http://dx.doi.org/10.1016/j.saa.2021.120252DOI Listing
August 2021

Weakly supervised cell instance segmentation under various conditions.

Med Image Anal 2021 Oct 22;73:102182. Epub 2021 Jul 22.

Department of Advanced Information Technology, Kyushu University, Fukuoka, Japan. Electronic address:

Cell instance segmentation is important in biomedical research. For living cell analysis, microscopy images are captured under various conditions (e.g., the type of microscopy and type of cell). Deep-learning-based methods can be used to perform instance segmentation if sufficient annotations of individual cell boundaries are prepared as training data. Generally, annotations are required for each condition, which is very time-consuming and labor-intensive. To reduce the annotation cost, we propose a weakly supervised cell instance segmentation method that can segment individual cell regions under various conditions by only using rough cell centroid positions as training data. This method dramatically reduces the annotation cost compared with the standard annotation method of supervised segmentation. We demonstrated the efficacy of our method on various cell images; it outperformed several of the conventional weakly-supervised methods on average. In addition, we demonstrated that our method can perform instance cell segmentation without any manual annotation by using pairs of phase contrast and fluorescence images in which cell nuclei are stained as training data.
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http://dx.doi.org/10.1016/j.media.2021.102182DOI Listing
October 2021

Wheat grain phenolics: a review on composition, bioactivity, and influencing factors.

J Sci Food Agric 2021 Jul 26. Epub 2021 Jul 26.

College of Agronomy/National Engineering Research Center for Wheat, Henan Agricultural University, Zhengzhou, China.

Wheat (Triticum aestivum L.) is a widely cultivated crop and one of the most commonly consumed food grains in the world. It possesses several nutritional elements. Increasing attention to wheat grain phenolics bioactivity is due to the increasing demand for foods with natural antioxidants. To provide a comprehensive understanding of phenolics in wheat grain, this review first summarizes the phenolics' form and distribution and the phenolic components identified in wheat grain. In particular, the biosynthesis path for phenolics is discussed, identifying some candidate genes involved in the biosynthesis of phenolic acids and flavonoids. After discussing the methods for determining antioxidant activity, the effect of genotypes, environmental conditions, and cultivation systems on grain phenolic component content are explored. Finally, the bioavailability of phenolics under different food processing method are reported and discussed. Future research is recommended to increase wheat grain phenolic content by genetic engineering, and to improve its bioavailability through proper food processing. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11428DOI Listing
July 2021

Adsorption properties of albumin and fibrinogen on hydrophilic/hydrophobic TiO surfaces: A molecular dynamics study.

Colloids Surf B Biointerfaces 2021 Jul 20;207:111994. Epub 2021 Jul 20.

Department of Engineering Mechanics, Tsinghua University, Beijing, 100084, China. Electronic address:

In serval experimental researches, UV-induced hydrophilicity enabled better hemocompatibility in the TiO surface, which was considered to be caused by the removal of the carboxylic acid contamination from the surface. In this paper, we altered the surface wetting property by applying the formate contamination on the rutile (110) surface, and systematically investigated the adsorption properties of albumin and fibrinogen on hydrophilic/hydrophobic TiO surface. Unique contacts were found between the charged residues and the hydrophilic surface, anchoring the protein on the surface. The small size and the heart shape of albumin make it easy to cross the stable water layers near the surface. Besides, albumin has a higher proportion of charged residues, so it can form more unique contacts on the hydrophilic surface. Therefore, the albumin tends to adsorb on the hydrophilic surface. For the hydrophobic surface, the water layers near the surface are weakened, which helps the fibrinogen diffusing to the surface and adjusting its orientation. Although the hydrophobic surface cannot form the unique contacts, the larger size of fibrinogen can provide more residues to form enough ordinary contacts after adjusting, and then achieves stable adsorption. Therefore, fibrinogen tends to adsorb on the hydrophobic surface.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111994DOI Listing
July 2021

Characterization of the blood and neutrophil-specific microbiomes and exploration of potential bacterial biomarkers for sepsis in surgical patients.

Immun Inflamm Dis 2021 Jul 20. Epub 2021 Jul 20.

Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Introduction: Recent studies have demonstrated the presence of a circulating microbiome in the blood of healthy subjects and chronic inflammatory patients. However, our knowledge regarding the blood microbiome and its potential roles in surgical patients remains very limited. The objective of this study was to determine the blood microbial landscape in surgical patients and to explore its potential associations with postoperative sepsis.

Materials And Methods: 2825 patients who underwent surgical treatments were screened for enrollment and 204 cases were recruited in this study. The patients were sub-grouped into noninfected, infected, sepsis, and septic shock according to postoperative clinical manifestations. A total of 222 blood samples were obtained for neutrophil isolation, DNA extraction and high-throughput sequencing, quantitative proteomics analysis, and flow cytometric analyses.

Results: Blood and neutrophils in surgical patients and healthy controls contained highly diverse microbiomes, mainly comprising Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. The majority (80.7%-91.5%) of the microbiomes were composed of gut-associated bacteria. The microbiomes in septic patients were significantly distinct from those of healthy controls, and marked differences in microbiome composition were observed between sepsis and septic shock groups. Several specific bacterial genera, including Flavobacterium, Agrococcus, Polynucleobacter, and Acidovorax, could distinguish patients with septic shock from those with sepsis, with higher area under curve values. Moreover, Agrococcus, Polynucleobacter, and Acidovorax were positively associated with the sequential (sepsis-related) organ failure assessment scores and/or acute physiology and chronic health examination scores in septic shock patients. The proteins involved in bactericidal activities of neutrophils were downregulated in septic patients.

Conclusions: We present evidence identifying significant changes of blood and neutrophil-specific microbiomes across various stages of sepsis, which might be associated with the progression of sepsis after surgical treatments. Several certain bacterial genera in blood microbiome could have potential as microbial markers for early detection of sepsis.
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http://dx.doi.org/10.1002/iid3.483DOI Listing
July 2021

Clinical implementation of automated treatment planning for whole-brain radiotherapy.

J Appl Clin Med Phys 2021 Sep 10;22(9):94-102. Epub 2021 Jul 10.

Department of Radiation Oncology, Hoag Hospital, Newport Beach, CA, USA.

The purpose of the study was to develop and clinically deploy an automated, deep learning-based approach to treatment planning for whole-brain radiotherapy (WBRT). We collected CT images and radiotherapy treatment plans to automate a beam aperture definition from 520 patients who received WBRT. These patients were split into training (n = 312), cross-validation (n = 104), and test (n = 104) sets which were used to train and evaluate a deep learning model. The DeepLabV3+ architecture was trained to automatically define the beam apertures on lateral-opposed fields using digitally reconstructed radiographs (DRRs). For the beam aperture evaluation, 1st quantitative analysis was completed using a test set before clinical deployment and 2nd quantitative analysis was conducted 90 days after clinical deployment. The mean surface distance and the Hausdorff distances were compared in the anterior-inferior edge between the clinically used and the predicted fields. Clinically used plans and deep-learning generated plans were evaluated by various dose-volume histogram metrics of brain, cribriform plate, and lens. The 1st quantitative analysis showed that the average mean surface distance and Hausdorff distance were 7.1 mm (±3.8 mm) and 11.2 mm (±5.2 mm), respectively, in the anterior-inferior edge of the field. The retrospective dosimetric comparison showed that brain dose coverage (D99%, D95%, D1%) of the automatically generated plans was 29.7, 30.3, and 32.5 Gy, respectively, and the average dose of both lenses was up to 19.0% lower when compared to the clinically used plans. Following the clinical deployment, the 2nd quantitative analysis showed that the average mean surface distance and Hausdorff distance between the predicted and clinically used fields were 2.6 mm (±3.2 mm) and 4.5 mm (±5.6 mm), respectively. In conclusion, the automated patient-specific treatment planning solution for WBRT was implemented in our clinic. The predicted fields appeared consistent with clinically used fields and the predicted plans were dosimetrically comparable.
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http://dx.doi.org/10.1002/acm2.13350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425887PMC
September 2021

Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy.

Pharmaceutics 2021 Jun 21;13(6). Epub 2021 Jun 21.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Due to their "tumor homing" and "immune privilege" characteristics, the use of mesenchymal stem cells (MSCs) has been proposed as a novel tool against cancer. MSCs are genetically engineered in vitro and then utilized to deliver tumoricidal agents, including prodrugs and bioactive molecules, to tumors. The genetic modification of MSCs can be achieved by various vectors, and in most cases viral vectors are used; however, viruses may be associated with carcinogenesis and immunogenicity, restricting their clinical translational potential. As such, nonviral vectors have emerged as a potential solution to address these limitations and have gradually attracted increasing attention. In this review, we briefly revisit the current knowledge about MSC-based cancer gene therapy. Then, we summarize the advantages and challenges of nonviral vectors for MSC transfection. Finally, we discuss recent advances in the development of new nonviral vectors, which have provided promising strategies to overcome obstacles in the gene modulation of MSCs.
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http://dx.doi.org/10.3390/pharmaceutics13060913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235299PMC
June 2021

Resveratrol ameliorates malathion-induced estrus cycle disorder through attenuating the ovarian tissue oxidative stress, autophagy and apoptosis.

Reprod Toxicol 2021 09 25;104:8-15. Epub 2021 Jun 25.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

Malathion is a high-efficiency organic phosphorus broad-spectrum insecticide which is commonly used in agricultural production, sanitation and epidemic prevention. Although the toxic effects of malathion on animal reproduction have been partially evaluated, its function, regulatory mechanism and antidote in estrus cycle and reproductive damage remain generally unclear. Here, the results showed that malathion disrupted the normal estrus cycle in mice, reduced the secretion of ovarian hormones, increased the amount of reactive oxygen species (ROS), and promoted autophagy and apoptosis in the ovary. Interestingly, we found that an antioxidant resveratrol could inhibit the disorders of estrus cycle and steroid hormone synthesis, reduced the abnormality of ROS accumulation, autophagy and apoptosis in malathion-exposed ovarian tissue. Furthermore, compared with those of the control group, malathion induced autophagy and apoptosis in the granular cells, whereas resveratrol attenuated these effects of malathion. Therefore, disadvantages of malathion exposure on estrus cycle disorder could partly reverse by resveratrol supplement. Overall, resveratrol may be a potential drug to prevent malathion-induced ovarian damages and estrus cycle disorder. Our findings provide new insights into ovarian response to malathion and resveratrol exposure.
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http://dx.doi.org/10.1016/j.reprotox.2021.06.015DOI Listing
September 2021

Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning.

Nat Biomed Eng 2021 06 15;5(6):586-599. Epub 2021 Jun 15.

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai, China.

The low abundance of circulating tumour DNA (ctDNA) in plasma samples makes the analysis of ctDNA biomarkers for the detection or monitoring of early-stage cancers challenging. Here we show that deep methylation sequencing aided by a machine-learning classifier of methylation patterns enables the detection of tumour-derived signals at dilution factors as low as 1 in 10,000. For a total of 308 patients with surgery-resectable lung cancer and 261 age- and sex-matched non-cancer control individuals recruited from two hospitals, the assay detected 52-81% of the patients at disease stages IA to III with a specificity of 96% (95% confidence interval (CI) 93-98%). In a subgroup of 115 individuals, the assay identified, at 100% specificity (95% CI 91-100%), nearly twice as many patients with cancer as those identified by ultradeep mutation sequencing analysis. The low amounts of ctDNA permitted by machine-learning-aided deep methylation sequencing could provide advantages in cancer screening and the assessment of treatment efficacy.
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http://dx.doi.org/10.1038/s41551-021-00746-5DOI Listing
June 2021

Neutrophil extracellular traps impair intestinal barrier functions in sepsis by regulating TLR9-mediated endoplasmic reticulum stress pathway.

Cell Death Dis 2021 06 11;12(6):606. Epub 2021 Jun 11.

Division of Trauma and Surgical Intensive Care Unit, Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, P. R. China.

Increased neutrophil extracellular traps (NETs) formation has been found to be associated with intestinal inflammation, and it has been reported that NETs may drive the progression of gut dysregulation in sepsis. However, the biological function and regulation of NETs in sepsis-induced intestinal barrier dysfunction are not yet fully understood. First, we found that both circulating biomarkers of NETs and local NETs infiltration in the intestine were significantly increased and had positive correlations with markers of enterocyte injury in abdominal sepsis patients. Moreover, the levels of local citrullinated histone 3 (Cit H3) expression were associated with the levels of BIP expression. To further confirm the role of NETs in sepsis-induced intestinal injury, we compared peptidylarginine deiminase 4 (PAD4)-deficient mice and wild-type (WT) mice in a lethal septic shock model. In WT mice, the Cit H3-DNA complex was markedly increased, and elevated intestinal inflammation and endoplasmic reticulum (ER) stress activation were also found. Furthermore, PAD4 deficiency alleviated intestinal barrier disruption and decreased ER stress activation. Notably, NETs treatment induced intestinal epithelial monolayer barrier disruption and ER stress activation in a dose-dependent manner in vitro, and ER stress inhibition markedly attenuated intestinal apoptosis and tight junction injury. Finally, TLR9 antagonist administration significantly abrogated NETs-induced intestinal epithelial cell death through ER stress inhibition. Our results indicated that NETs could contribute to sepsis-induced intestinal barrier dysfunction by promoting inflammation and apoptosis. Suppression of the TLR9-ER stress signaling pathway can ameliorate NETs-induced intestinal epithelial cell death.
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http://dx.doi.org/10.1038/s41419-021-03896-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195983PMC
June 2021

Interfacial sp C-O-Mo Hybridization Originated High-Current Density Hydrogen Evolution.

J Am Chem Soc 2021 Jun 8;143(23):8720-8730. Epub 2021 Jun 8.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Institute of Environmental and Applied Chemistry, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China.

High-current density (≥1 A cm) is a critical factor for large-scale industrial application of water-splitting electrocatalysts, especially seawater-splitting. However, it still remains a great challenge to reach high-current density due to the lack of active and stable intrinsic catalytic active sites in catalysts. Herein, we report an original three-dimensional self-supporting graphdiyne/molybdenum oxide (GDY/MoO) material for efficient hydrogen evolution reaction via a rational design of "sp C-O-Mo hybridization" on the interface. The "sp C-O-Mo hybridization" creates new intrinsic catalytic active sites (nonoxygen vacancy sites) and increases the amount of active sites (eight times higher than pure MoO). The "sp C-O-Mo hybridization" facilitates charge transfer and boosts the dissociation process of HO molecules, leading to outstanding HER activity with high-current density (>1.2 A cm) in alkaline electrolyte and a decent activity and stability in natural seawater. Our results show that high-current density electrocatalysts can be achieved by interfacial chemical bond engineering, three-dimensional structure design, and hydrophilicity optimization.
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http://dx.doi.org/10.1021/jacs.1c02831DOI Listing
June 2021

TaPHT1;9-4B and its transcriptional regulator TaMYB4-7D contribute to phosphate uptake and plant growth in bread wheat.

New Phytol 2021 09 2;231(5):1968-1983. Epub 2021 Jul 2.

The State Key Laboratory of Wheat and Maize Crop Science, College of Agronomy, Henan Agricultural University, Zhengzhou, 450002, China.

Efficient phosphate (Pi) uptake and utilisation are essential for promoting crop yield. However, the underlying molecular mechanism is still poorly understood in complex crop species such as hexaploid wheat. Here we report that TaPHT1;9-4B and its transcriptional regulator TaMYB4-7D function in Pi acquisition, translocation and plant growth in bread wheat. TaPHT1;9-4B, a high-affinity Pi transporter highly upregulated in roots by Pi deficiency, was identified using quantitative proteomics. Disruption of TaPHT1;9-4B function by BSMV-VIGS or CRISPR editing impaired wheat tolerance to Pi deprivation, whereas transgenic expression of TaPHT1;9-4B in rice improved Pi uptake and plant growth. Using yeast-one-hybrid assay, we isolated TaMYB4-7D, a R2R3 MYB transcription factor that could activate TaPHT1;9-4B expression by binding to its promoter. Silencing TaMYB4-7D decreased TaPHT1;9-4B expression, Pi uptake and plant growth. Four promoter haplotypes were identified for TaPHT1;9-4B, with Hap3 showing significant positive associations with TaPHT1;9-4B transcript level, growth performance and phosphorus (P) content in wheat plants. A functional marker was therefore developed for tagging Hap3. Collectively, our data shed new light on the molecular mechanism controlling Pi acquisition and utilisation in bread wheat. TaPHT1;9-4B and TaMYB4-7D may aid further research towards the development of P efficient crop cultivars.
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http://dx.doi.org/10.1111/nph.17534DOI Listing
September 2021

The outcomes in STEMI patients with high thrombus burden treated by deferred versus immediate stent implantation in primary percutaneous coronary intervention: a prospective cohort study.

Ann Transl Med 2021 Apr;9(7):573

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: No-/slow-reflow indicates worse outcomes in ST-elevation myocardial infarction (STEMI) patients with high thrombus burden. We examined whether deferred stenting (DS) strategy reduces no-/slow-reflow or major adverse cardiovascular events (MACEs) in primary percutaneous coronary intervention (pPCI) for patients with acute STEMI and high thrombus burden.

Methods: We performed an open-label, multi-center, prospective cohort study among eligible patients with acute STEMI and high thrombus burden who further received pPCI. All participants received PCI with DS (second procedure performed within 48-72 h) or immediate-stenting (IS) strategy. The primary outcome was the incidence of no-/slow-reflow. We evaluated MACEs and bleeding events during hospitalization and at 30- and 90-day follow-ups.

Results: We recruited 245 patients to this study, including 51 with DS and 194 with IS. Baseline clinical characters were comparable between the 2 strategies. Incidence of no-/slow-reflow defined by thrombolysis in myocardial infarction (TIMI) flow grade was not significantly different between the 2 strategies [DS: 5 (9.8%), IS: 33 (17.0%), P=0.21]. No-/slow-reflow by TIMI myocardial perfusion grade (TMPG) was less prevalent in DS [20 (39.2%) 107 (55.2%), P=0.04]. No significant differences were found in recurrence of myocardial infarction (P=0.56), cardiac death (P=0.37), all-cause mortality (P=0.37), heart failure-induced readmission (P=0.35), or bleeding (P=0.61) between the 2 strategies in-hospital, and at 30- and 90-day follow-up.

Conclusions: In STEMI patients with high thrombus burden who underwent pPCI, DS strategy reduced no-/slow-reflow of microcirculation. However, DS strategy did not reduce incidence of MACEs or bleeding.
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http://dx.doi.org/10.21037/atm-21-1130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105830PMC
April 2021

Convolutional neural network for estimating physical parameters from Newton's rings.

Appl Opt 2021 May;60(13):3964-3970

By analyzing Newton's rings, often encountered in interferometry, the parameters of spherical surfaces such as the rings' center and the curvature radius can be estimated. First, the classical convolutional neural networks, visual geometry group (VGG) network and U-Net, are applied to parameter estimation of Newton's rings. After these models are trained, the rings' center and curvature radius can be obtained simultaneously. Compared with previous analysis methods of Newton's rings, it is shown that the proposed method has higher precision, better immunity to noise, and lower time consumption. For a Newton's rings pattern of ${{640}} \times {{480}}$ pixels comprising ${-}{{5}}\;{\rm{dB}}$ Gaussian noise or 60% salt-and-pepper noise, the parameters can be estimated by the VGG model in 0.01 s, the error of the rings' center is less than one pixel, and the error of curvature radius is lower than 0.5%.
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http://dx.doi.org/10.1364/AO.422012DOI Listing
May 2021

Pearls & Oy-sters: Primary Pineal Melanoma With Leptomeningeal Carcinomatosis.

Neurology 2021 08 30;97(5):248-250. Epub 2021 Apr 30.

From the Departments of Neuro-Oncology (A.E.A., R.A.H.) and Melanoma Medical Oncology (I.C.G.O.), Division of Cancer Medicine, Departments of Head and Neck Surgery (N.A.-Z., M.-E.N.) and Neurosurgery (S.D.F.), Division of Surgery, Department of Neuroradiology, Division of Diagnostic Imaging (D.K.), Department of Radiation Oncology, Division of Radiation Oncology (C.W.), and Department of Pathology, Division of Pathology and Laboratory Medicine (G.F.), MD Anderson Cancer Center, Houston, TX.

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http://dx.doi.org/10.1212/WNL.0000000000012121DOI Listing
August 2021

Prediction of soft tissue sarcoma response to radiotherapy using longitudinal diffusion MRI and a deep neural network with generative adversarial network-based data augmentation.

Med Phys 2021 Jun 14;48(6):3262-3372. Epub 2021 May 14.

Physics and Biology in Medicine IDP, University of California, Los Angeles, CA, USA.

Purpose: The goal of this study was to predict soft tissue sarcoma response to radiotherapy (RT) using longitudinal diffusion-weighted MRI (DWI). A novel deep-learning prediction framework along with generative adversarial network (GAN)-based data augmentation was investigated for the response prediction.

Methods: Thirty soft tissue sarcoma patients who were treated with five-fraction hypofractionated radiation therapy (RT, 6Gy×5) underwent diffusion-weighted MRI three times throughout the RT course using an MR-guided radiotherapy system. Pathologic treatment effect (TE) scores, ranging from 0-100%, were obtained from the post-RT surgical specimen as a surrogate of patient treatment response. Patients were divided into three classes based on the TE score (TE ≤ 20%, 20% < TE < 90%, TE ≥ 90%). Apparent diffusion coefficient (ADC) maps of the tumor from the three time points were combined as 3-channel images. An auxiliary classifier generative adversarial network (ACGAN) was trained on 20 patients to augment the data size. A total of 15,000 synthetic images were generated for each class. A prediction model based on a previously described VGG-19 network was trained using the synthesized data, validated on five unseen validation patients, and tested on the remaining five test patients. The entire process was repeated seven times, each time shuffling the training, validation, and testing datasets such that each patient was tested at least once during the independent test stage. Prediction performance for slice-based prediction and patient-based prediction was evaluated.

Results: The average training and validation accuracies were 86.5% ± 1.6% and 84.8% ± 1.8%, respectively, indicating that the generated samples were good representations of the original patient data. Among the seven rounds of testing, slice by slice prediction accuracy ranged from 81.6% to 86.8%. The overall accuracy of the independent test sets was 83.3%. For patient-based prediction, 80% was achieved in one round and 100% was achieved in the remaining six rounds. The mean accuracy was 97.1%.

Conclusion: This study demonstrated the potential to use deep learning to predict the pathologic treatment effect from longitudinal DWI. Accuracies of 83.3% and 97.1% were achieved on independent test sets for slice-based and patient-based prediction respectively.
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http://dx.doi.org/10.1002/mp.14897DOI Listing
June 2021

SH3BGRL3, transcribed by STAT3, facilitates glioblastoma tumorigenesis by activating STAT3 signaling.

Biochem Biophys Res Commun 2021 06 8;556:114-120. Epub 2021 Apr 8.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma (GBM) is the most aggressive tumors of the central nervous system. Here, we report that SH3 binding glutamic acid-rich protein like 3 (SH3BGRL3) was extremely highly expressed in GBM and glioma stem cells. SH3BGRL3 high expression associates with worse survival of GBM patients. Functionally, Targeting SH3BGRL3 obviously impairs GSCs self-renewal in vitro. Most importantly, we first report that SH3BGRL3 is a direct transcriptional target gene of signal transducer and activator of transcription 3 (STAT3) and thereby activating STAT3 signaling in turn. Additionally, forced expression of the constitutively activated STAT3 (STAT3-C) rescued GSCs self-renewal inhibited by SH3BGRL3 silencing. Collectively, we first identified a critical positive feedback loop between SH3BGRL3 and STAT3, which facilitates the tumorigenic potential of GBM.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.165DOI Listing
June 2021

Topological Rainbow Concentrator Based on Synthetic Dimension.

Phys Rev Lett 2021 Mar;126(11):113902

Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Synthetic dimension provides a new platform for realizing topological photonic devices. Here, we propose a method to realize a rainbow concentrator of topological photonic states based on the synthetic dimension concept. The synthetic dimension is constructed using a translational degree of freedom of the nanostructures inside the unit cell of a two-dimensional photonic crystal. The translational deformation induces a nontrivial topology in the synthetic dimension, which gives rise to robust interface states at different frequencies. The topological rainbow can trap states with different frequencies, controlled by tuning the spatial modulation of interface state group velocities. The operation frequency as well as the bandwidth of the topological rainbow can be easily tuned by controlling the band gap of the photonic crystal. The topological principle can be applied to photonic crystals of any symmetry and arbitrary material composition, as long as a complete band gap exists. This Letter provides a new and general scheme for the realization of a topological rainbow concentrator and will be useful for the development of topological photonic devices.
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http://dx.doi.org/10.1103/PhysRevLett.126.113902DOI Listing
March 2021

Transcriptome-based analysis of resistance mechanism to black point caused by Bipolaris sorokiniana in wheat.

Sci Rep 2021 Mar 25;11(1):6911. Epub 2021 Mar 25.

Agronomy College/National Key Laboratory of Wheat and Maize Crop Science, Henan Agricultural University, No. 15 Longzi Lake University Zone, New East District of Zhengzhou, Zhengzhou, 450046, Henan, People's Republic of China.

Black point is a cereal disease caused by complex pathogens, of which the pathogenicity of Bipolaris sorokiniana is the most serious in wheat. Resistance to black point is quantitative in nature, and thus the mechanism is poorly understood. We conducted a comparative transcriptome analysis to identify differentially expressed genes (DEGs) in black point-slightly susceptible and -highly susceptible wheat lines at different timepoints following B. sorokiniana inoculation. DEGs associated with photosynthesis were upregulated in black point-slightly susceptible lines. The top Gene Ontology enrichment terms for biological processes were oxidation-reduction, response to cold, salt stress, oxidative stress, and cadmium ion; terms for cellular component genes were mainly involved in plasma membrane and cytoplasmic membrane-bounded vesicle, whereas those for molecular function were heme binding and peroxidase activity. Moreover, activities of antioxidant enzymes superoxide dismutase, catalase, and peroxidase were higher in slightly susceptible lines than those in highly susceptible lines (except peroxidase 12-24 days post-inoculation). Thus, resistance to B. sorokiniana-caused black point in wheat was mainly related to counteracting oxidative stress, although the specific metabolic pathways require further study. This study presents new insights for understanding resistance mechanisms of selected wheat lines to black point.
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http://dx.doi.org/10.1038/s41598-021-86303-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994838PMC
March 2021

Liver proteomics analysis reveals abnormal metabolism of bile acid and arachidonic acid in Chinese hamsters with type 2 diabetes mellitus.

J Proteomics 2021 05 17;239:104186. Epub 2021 Mar 17.

Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan 030001, China. Electronic address:

Non-obese, spontaneous, and genetically predisposed type 2 diabetic Chinese hamsters exhibit metabolic abnormalities similar to those observed in human T2DM. Here, tandem mass tag (TMT)-based quantitative proteomics technology was used to screen and identify differentially abundant proteins in the liver that are associated with diabetes in Chinese hamsters. GO and KEGG pathway enrichment analysis were conducted to validate the findings, as well as qRT-PCR and western blotting. In total, 103 proteins were identified in the livers of diabetic hamsters, of which 48 were up-regulated and 55 were down-regulated. KEGG pathway enrichment analysis further demonstrated that linoleic acid metabolism, arachidonic acid metabolism, bile secretion, and other pathways were affected. Moreover, AQP9 and EPHX1 were significantly down-regulated in the bile secretion pathway, whereas PTGES2, Cyp2c27, and Cyp2c70 were associated with the arachidonic acid metabolic pathway. Serum levels of bile acid (BA) and arachidonic acid (AA) in diabetic Chinese hamsters were significantly higher than those in control hamsters. Cumulatively, our findings indicate that the five candidate proteins may be associated with abnormal BA and AA metabolism, suggesting their involvement in pathological changes in the livers of Chinese hamsters with T2DM. SIGNIFICANCE: The liver proteomics of Chinese hamsters describes differentially abundant proteins associated with T2DM, while promoting this animal model as an appropriate and ideal platform for investigating underlying molecular mechanisms of T2DM. This study reveals abnormal bile acid and arachidonic acid metabolism in T2DM hamsters, which may provide insights for studying the relationship between candidate proteins and KEGG pathways to elucidate the underlying molecular mechanism associated with T2DM.
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http://dx.doi.org/10.1016/j.jprot.2021.104186DOI Listing
May 2021

Topological rainbow based on graded topological photonic crystals.

Opt Lett 2021 Mar;46(6):1237-1240

Topological photonic crystal provides a robust platform for nanophotonic devices. However, few reports have been found to realize multiple frequency routing based on topological photonic states, which have restricted further applications in the field of nanophotonic devices. Here, for the first time, to the best of our knowledge, we propose an efficient method to realize a topological rainbow based on graded dielectric topological photonic crystals, which are constructed by changing the degree of lattice contraction and expansion. The topological edge states of different frequencies are separated and trapped at different positions. The all-dielectric planar nanostructures of graded topological photonic crystals are low-loss, robust, and easy for integration. This Letter plays a key role in the use of robust nanophotonic wavelength routers, optical storage, and optical buffers.
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http://dx.doi.org/10.1364/OL.419271DOI Listing
March 2021

SH3BGRL2 functions as a crucial tumor suppressor in glioblastoma tumorigenesis.

Biochem Biophys Res Commun 2021 04 19;547:148-154. Epub 2021 Feb 19.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma is the most common and severe primary intrinsic tumor of the central nervous system. Glioblastoma harbors glioma stem cells (GSCs) as it not only possesses self-renewal and differentiation properties but also accounts for significant chemotherapy resistance and recurrence. Thus, targeting GSCs may be essential in overcoming the resistance and recurrence thereby improving GBM treatment. However, the underlying mechanism to sustain GSCs remains largely unknown. Here, we report that SH3 domain binding glutamate-rich protein like 2 (SH3BGRL2) is weakly expressed in glioblastoma multiforme (GBM) and isocitrate dehydrogenase1 (IDH1) wildtype GBM and correlated with glioma patients' poor prognosis. Moreover, ectopic expression of SH3BGRL2 significantly inhibited GBM cell growth, migration, and GSCs self-renewal in vitro as well as tumor growth in vivo. Additionally, we found that SH3BGRL2 suppressed SOX2 and CD133 expression, which are key regulators involved in GSCs self-renewal. Collectively, our findings shed additional light on SH3BGRL2 has potential to serve as a biomarker and a potent therapeutic target for patients with glioma.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.035DOI Listing
April 2021

MicroRNA-545 suppresses progression of ovarian cancer through mediating PLK1 expression by a direct binding and an indirect regulation involving KDM4B-mediated demethylation.

BMC Cancer 2021 Feb 15;21(1):163. Epub 2021 Feb 15.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, No.2, Jingba Road, Zhengzhou, 450014, Henan, People's Republic of China.

Background: Ovarian cancer (OC) is a life-threatening gynecological malignancy where dysregulation of microRNAs (miRNAs) is frequently implicated. This study focuses on the function of miR-545 on OC development and the molecules involved.

Methods: miR-545 expression in OC tissues and cell lines was determined, and its link to the survival of patients was analyzed. Altered expression of miR-545 was induced to determine its role in proliferation, apoptosis, migration and invasion of OC cells and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs). The targeting mRNAs of miR-545 were predicted and validated through luciferase assays. Gain-of-function studies of KDM4B and PLK1 were performed to explore their involvements in OC development. In vivo experiments were conducted by inducing xenograft tumors in nude mice.

Results: Poor expression of miR-545 was found in OC tissues and cells compared to the normal ones and it indicated unfavorable prognosis in patients. Overexpression of miR-545 suppressed growth, migration, invasion and angiogenesis of OC cells as well as the angiogenesis ability of HUVECs. miR-545 was found to target mRNAs of KDM4B and PLK1, while KDM4B promoted the transcription of the PLK1 promoter through demethylation of H3K9me3. Either overexpression of KDM4B or PLK1 partially blocked the inhibitory effects of miR-545 mimic on OC cell growth, especially the former one. The in vitro results were reproduced in vivo.

Conclusion: This study evidenced that miR-545 suppresses progression of OC through mediating PLK1 expression by a direct binding and an indirect regulation involving KDM4B-mediated demethylation.
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http://dx.doi.org/10.1186/s12885-021-07830-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885496PMC
February 2021

Discovery and validation of methylation signatures in blood-based circulating tumor cell-free DNA in early detection of colorectal carcinoma: a case-control study.

Clin Epigenetics 2021 02 3;13(1):26. Epub 2021 Feb 3.

Colorectal Surgery Department, Changhai Hospital, Naval Medical University, Changhai Road No.168, Yangpu District, Shanghai, 200433, China.

Background: Early detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients' compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC.

Results: In total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2-93.7%) and the sensitivity was 88.6% (82.4-93.2%). In terms of different stages, the sensitivities were 79.4% (62.1-91.2%) in patients with stage I, 88.9% (77.3-95.8%) in patients with stage II, 91.4% (76.9-98.2%) in patients with stage III and 96.2% (80.3-99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1-97.0%) and sensitivity of 83.6% (72.5-91.6%). Sensitivities for stage I-III were 87.0% (79.7-92.4%) in the training set and 82.5% (70.2-91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2-11.2%) in healthy control, 30.8% (19.9-43.5%) in benign colorectal disease and 58.3% (27.5-84.7%) in advanced adenoma, while the sensitivities of stage I-IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8-91.2%] versus 41.2% [34.6-48.1%], P < 0.001) under comparable specificity (90.1% [85.4-93.7%] versus 90.6% [86.0-94.1%]).

Conclusions: Together our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies.
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http://dx.doi.org/10.1186/s13148-020-00985-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856810PMC
February 2021

On the Structures of Thorium Fluoride and Oxyfluoride Anions in Molten FLiBe and FLiNaK.

J Phys Chem B 2021 Feb 3;125(6):1640-1646. Epub 2021 Feb 3.

Department of Radiochemistry, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

The structures of thorium fluoride and oxyfluoride ions in molten FLiBe-ThF and FLiNaK-ThF were investigated by Raman spectroscopy and density functional theory calculations. Thorium fluorides are present in the form of ThF () and ThF () in molten FLiNaK-ThF. Similar speciation was identified in FLiBe-ThF, and the thorium fluoride anions are in equilibrium with free F ions and beryllium fluoride anions, which are responsible for the red shift of the beryllium fluoride bands in the Raman spectra. With the addition of LiO into the FLiNaK-ThF and FLiBe-ThF melts, the ThOF anion with a linear Th-O-Th geometry was formed at the expense of thorium fluoride anions. The beryllium fluoride bands in the Raman spectra of FLiBe-ThF exhibit a blue shift upon ThOF formation, which results from the release of free F ions that can further react with beryllium fluoride. Insoluble thorium oxides were found in the FLiNaK and FLiBe melts at a LiO concentration of 15 mol %, and the ThOF anion is, therefore, a bridge connecting the soluble thorium fluorides and insoluble thorium oxides in molten fluorides.
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http://dx.doi.org/10.1021/acs.jpcb.0c10197DOI Listing
February 2021
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