Publications by authors named "Lili He"

203 Publications

Diffuse white matter abnormality in very preterm infants at term reflects reduced brain network efficiency.

Neuroimage Clin 2021 Jun 25;31:102739. Epub 2021 Jun 25.

Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. Electronic address:

Between 50 and 80% of very preterm infants (<32 weeks gestational age) exhibit increased white matter signal intensity on T2-weighted MRI at term-equivalent age, known as diffuse white matter abnormality (DWMA). A few studies have linked DWMA with microstructural abnormalities, but the exact relationship remains poorly understood. We related DWMA extent to graph theory measures of network efficiency at term in a representative cohort of 343 very preterm infants. We performed anatomic and diffusion MRI at term and quantified DWMA volume with our novel, semi-automated algorithm. From diffusion-weighted structural connectomes, we calculated the graph theory metrics local efficiency and clustering coefficient, which measure the ability of groups of nodes to perform specialized processing, and global efficiency, which assesses the ability of brain regions to efficiently combine information. We computed partial correlations between these measures and DWMA volume, adjusted for confounders. Increasing DWMA volume was associated with decreased global efficiency of the entire very preterm brain and decreased local efficiency and clustering coefficient in a variety of regions supporting cognitive, linguistic, and motor function. We show that DWMA is associated with widespread decreased brain network efficiency, suggesting that it is pathologic and likely has adverse developmental consequences.
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http://dx.doi.org/10.1016/j.nicl.2021.102739DOI Listing
June 2021

Identification of MicroRNAs in (DC.) Danser Seeds under Cold Stress.

Biomed Res Int 2021 30;2021:5585884. Epub 2021 May 30.

Guangxi Botanical Garden of Medicinal Plants, Nanning, China 530023.

(DC.) Danser, a parasitic plant that belongs to the Loranthaceae family, has a long history of being used in the Chinese medicine. We observed that the loranthus seeds were sensitive to temperature and could lose viability below 0°C quickly. Thus, we performed small RNA sequencing to study the microRNA (miRNA) regulation in the loranthus seeds under cold stress. In total, we identified 600 miRNAs, for the first time, in the loranthus seeds under cold stress. Then, we detected 224, 229, and 223 miRNAs (TPM > 1) in A0 (control), A1 (cold treatment for 12 h at 0°C), and A2 (cold treatment for 36 h at 0°C), respectively. We next identified 103 differentially expressed miRNAs (DEmiRs) in the loranthus seeds in response to cold. Notably, miR408 was upregulated during the cold treatment, which can regulate genes encoding phytocyanin family proteins and phytophenol oxidases. Some DEmiRs were specific to A1 and may function in early response to cold, such as gma-miR393b-3p, miR946, ath-miR779.2-3p, miR398, and miR9662. It is interesting that ICE3, IAA13, and multiple transcription factors (e.g., WRKY and CRF4 and TCP4) regulated by the DEmiRs have been reported to respond cold in other plants. We further identified 4, 3, and 4 DEmiRs involved in the pathways "responding to cold," "responding to abiotic stimulus," and "seed development/germination," respectively. qRT-PCR was used to confirm the expression changes of DEmiRs and their targets in the loranthus seeds during the cold treatment. This is the first time to study cold-responsive miRNAs in loranthus, and our findings provide a valuable resource for future studies.
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http://dx.doi.org/10.1155/2021/5585884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188600PMC
May 2021

Automatic Segmentation of Diffuse White Matter Abnormality on T2-weighted Brain MR Images Using Deep Learning in Very Preterm Infants.

Radiol Artif Intell 2021 May 3;3(3):e200166. Epub 2021 Feb 3.

Imaging Research Center, Department of Radiology (H.L., L.H.), and Perinatal Institute (H.L., V.S.P.I., N.A.P., L.H.), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 5033, Cincinnati, OH 45229; Department of Electronic Engineering and Computing Systems, University of Cincinnati, Cincinnati, Ohio (M.C.); Deep MRI Imaging, Lewes, Del (J.W.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (N.A.P., L.H.).

About 50%-80% of very preterm infants (VPIs) (≤ 32 weeks gestational age) exhibit diffuse white matter abnormality (DWMA) on their MR images at term-equivalent age. It remains unknown if DWMA is associated with developmental impairments, and further study is warranted. To aid in the assessment of DWMA, a deep learning model for DWMA quantification on T2-weighted MR images was developed. This secondary analysis of prospective data was performed with an internal cohort of 98 VPIs (data collected from December 2014 to April 2016) and an external cohort of 28 VPIs (data collected from January 2012 to August 2014) who had already undergone MRI at term-equivalent age. Ground truth DWMA regions were manually annotated by two human experts with the guidance of a prior published semiautomated algorithm. In a twofold cross-validation experiment using the internal cohort of 98 infants, the three-dimensional (3D) ResU-Net model accurately segmented DWMA with a Dice similarity coefficient of 0.907 ± 0.041 (standard deviation) and balanced accuracy of 96.0% ± 2.1, outperforming multiple peer deep learning models. The 3D ResU-Net model that was trained with the whole internal cohort ( = 98) was further tested on an independent external test cohort ( = 28) and achieved a Dice similarity coefficient of 0.877 ± 0.059 and balanced accuracy of 92.3% ± 3.9. The externally validated 3D ResU-Net deep learning model for accurately segmenting DWMA may facilitate the clinical diagnosis of DWMA in VPIs. Brain/Brain Stem, Convolutional Neural Network (CNN), MR-Imaging, Pediatrics, Segmentation, Supervised learning © RSNA, 2021.
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http://dx.doi.org/10.1148/ryai.2021200166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166113PMC
May 2021

Combined Treatment of Cinobufotalin and Gefitinib Exhibits Potent Efficacy against Lung Cancer.

Evid Based Complement Alternat Med 2021 20;2021:6612365. Epub 2021 Mar 20.

Department of Respiratory Neurology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, China.

This study aimed to evaluate the efficacy of cinobufotalin combined with gefitinib in the treatment of lung cancer. A549 cells were treated with gefitinib, cinobufotalin, or cinobufotalin plus gefitinib. MTT assay, annexin-V/PI staining and flow cytometry, TUNEL staining, DCFH-DA staining, Western blot, and real-time RT-PCR were performed to investigate the synergistic inhibitory effect of cinobufotalin combined with gefitinib on the growth of A549 cells. Results showed that cinobufotalin synergized with gefitinib displayed inhibited cell viability and enhanced apoptosis in the combination group. Cinobufotalin combined with gefitinib induced a significant enhancement in reactive oxygen species (ROS) production accompanied by cell cycle arrest in the S phase arrest, characterized by upregulation of p21 and downregulation of cyclin A, cyclin E, and CDK2. Besides, cinobufotalin plus gefitinib downregulated the levels of HGF and c-Met. In summary, cinobufotalin combined with gefitinib impedes viability and facilitates apoptosis of A549 cells, indicating that the combined therapy might be a new promising treatment for lung cancer patients who are resistant to gefitinib.
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http://dx.doi.org/10.1155/2021/6612365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189783PMC
March 2021

In situ and real time investigation of foliarly applied silver nanoparticles on and in spinach leaves by surface enhanced Raman spectroscopic mapping.

Anal Methods 2021 06 28;13(23):2567-2574. Epub 2021 May 28.

Department of Food Science, University of Massachusetts, 240 Chenoweth Laboratory, 102 Holdsworth Way, Amherst, Massachusetts 01003, USA.

Understanding the behavior and biological fate of silver nanoparticles (AgNPs) applied on plant surfaces is significant for their risk assessment. Our study's objective is to investigate the interactions between AgNPs and plant biomolecules as well as to monitor and quantify the penetration of AgNPs in spinach by an in situ and real-time surface enhanced Raman spectroscopic (SERS) mapping technique. AgNPs (2 μg per leaf) of different surface coatings (citrate, CIT, and polyvinylpyrrolidone, PVP) and sizes (40 and 100 nm) were foliarly applied onto spinach leaves with different exposure times (1-48 h). Cysteine is the major biomolecule that interacts with AgNPs in spinach based on the in situ and in vitro SERS pattern recognition. The interaction between CIT-AgNPs and cysteine happened in as early as 1 h after AgNP foliar deposition, which is faster than the interaction between PVP-AgNPs and cysteine. Also, the SERS depth mapping shows that particle size rather than surface coating determines the penetration capability of AgNPs in spinach, in which 40 nm AgNPs show a deeper penetration than the 100 nm ones. Last but not least, based on the results of SERS mapping, we detected significantly higher amounts of 40 nm CIT-/PVP-AgNPs than 100 nm CIT-AgNPs internalized in the leaf tissues after 1 h exposure. The estimated percentage of internalized AgNPs (0.2-0.8%) was significantly smaller than that of the total residual Ag (9-12%), indicating the potential transformation of the AgNPs into other Ag species inside the plant tissues. This study facilitates a better understanding of the behavior and biological fate of AgNPs in plant tissues.
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http://dx.doi.org/10.1039/d1ay00346aDOI Listing
June 2021

Chemotaxonomy of Aster species from the Qinghai-Tibetan Plateau based on metabolomics.

Phytochem Anal 2021 May 11. Epub 2021 May 11.

Institute of Qinghai-Tibetan Plateau, Southwest Minzu University, Chengdu, Sichuan Province, China.

Introduction: The genus Aster plants have been widely used for thousands of years in the Qinghai-Tibetan Plateau for the clearing of heat, detoxification, and the treatment of seasonal pandemic diseases. Although the presence of several flavonoid compounds in Aster has been reported by previous studies, the diversity of secondary metabolites within and among species is relatively unknown.

Objective: The metabolite profile of one Aster species was systematically compared with those of other taxa to find potential chemotaxonomic markers, delimit species, and assess chemodiversity.

Method: Samples of the above-ground parts of 11 Aster species were collected and their metabolites were analysed by ultra-high performance liquid chromatography with photodiode array detection and quadrupole time-of-flight tandem mass spectrometry. Unsupervised principal component analysis, supervised orthogonal partial least-squares discriminant analysis, heatmap analysis, and hierarchical cluster analysis were employed to analyse 95 representative samples from 11 Aster species and determine species-specific chemical markers based on a metabolomics database.

Results: Six phenolic acids and flavonoids were detected and quantified in all Aster species, suggesting that these compounds may be common constituents in the Aster genus. Metabolite analysis showed terpenoid compounds to be potential chemical markers for interspecies differentiation. Ent-kaurane-type diterpenoid glycosides were the main class of compounds in all Aster species except for A. farreri, which mainly contained oleanane-type pentacyclic triterpenoids. Diterpenoid glycosides were low-content chemotaxonomic markers and were detected for the first time in Aster species from the Qinghai-Tibetan Plateau.

Conclusion: Chemotaxonomy and metabolomics were used to support the phylogenic relationships of the Aster genus.
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http://dx.doi.org/10.1002/pca.3058DOI Listing
May 2021

Seed Priming with Sorghum Water Extract Improves the Performance of Camelina ( (L.) Crantz.) under Salt Stress.

Plants (Basel) 2021 Apr 12;10(4). Epub 2021 Apr 12.

Agronomic Research Institute, Ayub Agricultural Research Institute, Faisalabad 38040, Pakistan.

Seed priming with sorghum water extract (SWE) enhances crop tolerance to salinity stress; however, the application of SWE under salinity for camelina crop has not been documented so far. This study evaluated the potential role of seed priming with SWE in improving salt stress tolerance in camelina. Primed (with 5% SWE and distilled water-hydropriming) and nonprimed seeds were sown under control (no salt) and salt stress (10 dS m) conditions. Salinity reduced camelina's emergence and growth, while seed priming with SWE improved growth under control and stress conditions. Under salt stress, seed priming with SWE enhanced emergence percentage (96.98%), increased root length (82%), shoot length (32%), root dry weight (75%), shoot dry weight (33%), α-amylase activity (66.43%), chlorophyll content (60-92%), antioxidant enzymes activity (38-171%) and shoot K ion (60%) compared with nontreated plants. Similarly, under stress conditions, hydrogen peroxide, malondialdehyde (MDA) content, and shoot Na ion were reduced by 60, 31, and 40% by seed priming with SWE, respectively, over the nonprimed seeds. Therefore, seed priming with SWE may be used to enhance the tolerance against salt stress in camelina.
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http://dx.doi.org/10.3390/plants10040749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069245PMC
April 2021

Author Correction: Identifying threshold sizes for enlarged abdominal lymph nodes in different age ranges from about 200,000 individual's data.

Sci Rep 2021 Apr 21;11(1):9069. Epub 2021 Apr 21.

Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, 201102, People's Republic of China.

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http://dx.doi.org/10.1038/s41598-021-88764-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060269PMC
April 2021

Current and emerging artificial intelligence applications for pediatric abdominal imaging.

Pediatr Radiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA.

Artificial intelligence (AI) uses computers to mimic cognitive functions of the human brain, allowing inferences to be made from generally large datasets. Traditional machine learning (e.g., decision tree analysis, support vector machines) and deep learning (e.g., convolutional neural networks) are two commonly employed AI approaches both outside and within the field of medicine. Such techniques can be used to evaluate medical images for the purposes of automated detection and segmentation, classification tasks (including diagnosis, lesion or tissue characterization, and prediction), and image reconstruction. In this review article we highlight recent literature describing current and emerging AI methods applied to abdominal imaging (e.g., CT, MRI and US) and suggest potential future applications of AI in the pediatric population.
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http://dx.doi.org/10.1007/s00247-021-05057-0DOI Listing
April 2021

Recent advances in dual recognition based surface enhanced Raman scattering for pathogenic bacteria detection: A review.

Anal Chim Acta 2021 May 4;1157:338279. Epub 2021 Feb 4.

School of Food and Biological Engineering, Shaanxi University of Science & Technology, Xi'an, 710021, China. Electronic address:

Rapid and reliable detection of pathogenic bacteria at the early stage represents a highly topical research area for food safety and public health. Although culture based method is the gold standard method for bacteria detection, recent techniques have promoted the development of alternative methods, such as surface enhanced Raman scattering (SERS). SERS provides additional advantages of high speed, simultaneous detection and characterization, multiplex analysis, and comparatively low cost. However, conventional SERS methods for bacteria detection are facing limitations of low sensitivity, susceptible to matrix interference, and poor accuracy. In recent years, specific detection of pathogenic bacteria with dual recognition based SERS methods has attracted increasing attentions. These methods include two steps recognition of target bacteria, and integrate the functions of target separation and detection. Considering their merits of excellent specificity, ultrahigh sensitivity, multiplex detection capability, and potential for on-site applications, these methods are promising alternatives for rapid and reliable detection of pathogenic bacteria. Herein, this review aims to summarize the recent advances in dual recognition based SERS methods for specific detection of pathogenic bacteria. Their advantages and limitations are discussed, and further perspectives are tentatively given. This review provides new insights into the application of SERS as a reliable tool for pathogenic bacteria detection.
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http://dx.doi.org/10.1016/j.aca.2021.338279DOI Listing
May 2021

Fortification of Plant-Based Milk with Calcium May Reduce Vitamin D Bioaccessibility: An Digestion Study.

J Agric Food Chem 2021 Apr 31;69(14):4223-4233. Epub 2021 Mar 31.

Biopolymers and Colloids Laboratory, Department of Food Science, University of Massachusetts, Amherst, Massachusetts 01003, United States.

Many plant-based milks lack key micronutrients found in bovine milk, such as calcium and vitamin D. In this study, we fortified almond milk with these two micronutrients and used a standardized gastrointestinal model to examine the impact of product formulation on their bioaccessibility. The impact of different forms (CaCl versus CaCO) and concentrations (0, 1, or 2 g per 240 mL) of calcium on the physicochemical properties, lipid digestibility, and vitamin D bioaccessibility was examined. Soluble calcium (CaCl) promoted particle aggregation by reducing the electrostatic repulsion, while colloidal calcium (CaCO) did not because there were fewer free calcium ions. High levels of calcium (soluble or insoluble) reduced vitamin D bioaccessibility, which was attributed to insoluble calcium soap formation in the small intestine. Calcium bioaccessibility was higher for CaCO than CaCl. These findings are useful for the development of nutritionally fortified plant-based milks with improved physicochemical and nutritional properties.
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http://dx.doi.org/10.1021/acs.jafc.1c01525DOI Listing
April 2021

Diagnostic performance of lung ultrasound for transient tachypnea of the newborn: A meta-analysis.

PLoS One 2021 29;16(3):e0248827. Epub 2021 Mar 29.

Department of Radiology, Children's Hospital of Fudan University, Shanghai, China.

Several recent studies demonstrated that lung ultrasound could achieve desired diagnostic accuracy for transient tachypnea of the neonate (TTN). However, the diagnostic performance of lung ultrasound for TTN has not been systematically studied to date. This meta-analysis aimed to investigate the performance of lung ultrasound in diagnosing TTN. The relevant literature was searched in PubMed, Medline, the Cochrane Library, and Embase databases without any restriction in terms of language and time until January 31, 2021. Studies that assessed the diagnostic performance of lung ultrasound for TTN were included. Seven studies with 1514 participants were summarized. The lung ultrasound provided more accurate performance for diagnosing TTN with pooled sensitivity and specificity of 0.67 [95% confidence interval (CI) = 0.63-0.71] and 0.97 (95% CI = 0.95-0.98), respectively. A higher summarized area under the summary receiver operating characteristic curve was observed as 0.9906. Lower sensitivity and area under the curve (AUC) of B-lines for TTN were observed as 0.330 (95% CI = 0.27-0.38) and 0.5000, respectively. Lung ultrasound provided highly accurate AUC, sensitivity, and specificity in detecting TTN. Large-scale studies are warranted in the future to confirm these results.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248827PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006999PMC
March 2021

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes.

Beilstein J Org Chem 2021 12;17:711-718. Epub 2021 Mar 12.

Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, P.R. China.

The diazabicyclooctane (DBO) scaffold is the backbone of non-β-lactam-based second generation β-lactamase inhibitors. As part of our efforts, we have synthesized a series of DBO derivatives - containing amidine substituents at the C2 position of the bicyclic ring. These compounds, alone and in combination with meropenem, were tested against ten bacterial strains for their antibacterial activity in vitro. All compounds did not show antibacterial activity when tested alone (MIC >64 mg/L), however, they exhibited a moderate inhibition activity in the presence of meropenem by lowering its MIC values. The compound proved most potent among the other counterparts against all bacterial species with MIC from <0.125 mg/L to 2 mg/L, and is comparable to avibactam against both strains with a MIC value of <0.125 mg/L.
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http://dx.doi.org/10.3762/bjoc.17.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961884PMC
March 2021

Synthesis and antibacterial evaluation of new monobactams.

Bioorg Med Chem Lett 2021 05 24;39:127878. Epub 2021 Feb 24.

Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, PR China. Electronic address:

Monobactams play an important role in antibiotic drug discovery. Based on the structural characteristics of aztreonam and its biological targets, six new monobactam derivatives (2a-c and 3a-c) were synthesized and their in vitro antibacterial activities were investigated. Compounds 2a-c showed higher activities against tested gram-negative bacteria than that of parent aztreonam. Monobactam 2c exhibited the most potent activities, with MIC ranging from 0.25 to 2 μg/mL against most bacteria.
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http://dx.doi.org/10.1016/j.bmcl.2021.127878DOI Listing
May 2021

SERS imaging analyses of bacteria cells among plant tissues.

Talanta 2021 Apr 16;225:122008. Epub 2020 Dec 16.

Department of Food Science, University of Massachusetts, Amherst, MA, 01003, USA. Electronic address:

A chemical imaging method to mass surveil bacteria cells among plant tissues in situ is reported. Bacteria cells were pre-labeled with 3-mercaptophenylboronic acid for complexation with gold nanoparticles. Surface-enhanced Raman spectra were collated en masse to generate panoramic chemical images of bacteria populations. The approach was successfully employed to study the distribution of mass bacteria populations directly on and in selected plant tissues. This study demonstrates the great potential with which SERS imaging can be utilized for the study of bacterial cells among complex matrices, in some ways that are superior to electron and fluorescent microscopies.
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http://dx.doi.org/10.1016/j.talanta.2020.122008DOI Listing
April 2021

Association between NER pathway gene polymorphisms and neuroblastoma risk in an eastern Chinese population.

Mol Ther Oncolytics 2021 Mar 19;20:3-11. Epub 2020 Dec 19.

Department of Pathology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China.

Neuroblastoma is a common childhood malignancy. Nucleotide excision repair (NER) polymorphisms have been shown to influence cancer susceptibility by modifying DNA repair efficiency. To investigate the association of NER gene polymorphisms with neuroblastoma risk, we constructed a three-center case-control study. A total of 19 candidate single-nucleotide polymorphisms (SNPs) in NER genes were analyzed. Odds ratios (ORs) and 95% confidential intervals (CIs) were calculated to evaluate the associations. We identified five independent SNPs that were significantly associated with neuroblastoma risk, including rs1800975 (dominant model: adjusted OR = 0.73, 95% CI = 0.55-0.98, p = 0.033), rs3176752 (recessive model: adjusted OR = 2.78, 95% CI = 1.12-6.91, p = 0.028), rs3810366 (dominant: adjusted OR = 1.44, 95% CI = 1.05-1.97, p = 0.022; recessive: adjusted OR = 1.58, 95% CI = 1.18-2.11, p = 0.002), rs238406 (dominant: adjusted OR = 0.64, 95% CI = 0.48-0.84, p = 0.002; recessive: adjusted OR = 0.67, 95% CI = 0.48-0.94, p = 0.021), and rs2094258 (recessive: adjusted OR = 1.44, 95% CI = 1.03-2.04, p = 0.036). Stratified analysis was carried out. Furthermore, these findings were strengthened by false-positive report probability (FPRP) analysis and expression quantitative trait loci (eQTL) analysis. In conclusion, our study indicates that five SNPs in NER genes are correlated with neuroblastoma susceptibility in the eastern Chinese population, providing novel insight into the genetic underpinnings of neuroblastoma. However, further large-scale studies are required to verify these findings.
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http://dx.doi.org/10.1016/j.omto.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851491PMC
March 2021

Identifying threshold sizes for enlarged abdominal lymph nodes in different age ranges from about 200,000 individual's data.

Sci Rep 2021 Jan 19;11(1):1762. Epub 2021 Jan 19.

Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, 201102, People's Republic of China.

The threshold size for enlarged abdominal lymph nodes (E-ALNs), a common pediatric disorder, has yet to be standardized. According to the maximum short-axis diameter, this study divided ALNs into Grade A (≥ 10 mm), Grade B (8-10 mm), Grade C (5-8 mm), and Grade D (< 5 mm, normal). To identify the threshold size for E-ALNs, the prevalence of each grade was compared between asymptomatic individuals and symptomatic (e.g., abdominal pain) individuals without other diseases (e.g., appendicitis) that could explain the symptoms for different ages using data from > 200,000 individuals. The results showed the following: (1) For ages 1-3 years, the recommended threshold size is 8 mm, as the differences in the prevalence between the two groups were nonsignificant for Grade C but significant (p < 0.05) for both Grades A and B. (2) For ages 3-14 years, the recommended threshold size is 5 mm, as the differences between the two groups were significant (p < 0.05) for Grades A, B, and C. (3) The prevalence of Grades A, B, and C was very low for ages 0-1 years and high for ages 1-6 years. (4) The prevalence for males was generally higher than that for females for Grades A and B.
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http://dx.doi.org/10.1038/s41598-021-81339-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815733PMC
January 2021

Aromatin D-J: Seven previously undescribed labdane diterpenoids isolated from Blumea aromatica.

Phytochemistry 2021 Apr 15;184:112659. Epub 2021 Jan 15.

Guangxi Botanical Garden of Medicinal Plants, Chang Gang Road 189, Nanning, 530023, Guangxi Province, China.

Blumea aromatica is a traditional Chinese medicine used for treating various diseases such as rheumatoid arthritis, eczema, and pruritus. Previous studies on B. aromatica used a mass defect-filtering strategy via the ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and reported the presence of several labdane diterpenoids (LADs). To determine the actual structures of these LADs and investigate their biological activities, seven previously undescribed LADs (aromatin D-J) were isolated from the whole B. aromatica herb. The structures of these isolated compounds were characterized using high-resolution mass spectrometry and extensive 1D and 2D NMR analyses. In addition, the absolute configurations of these compounds were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra as well as using X-ray crystallographic analysis. All isolated compounds were evaluated for their ability to activate adenylate cyclase by measuring the levels of cyclic adenosine 3',5'-monophosphate (cAMP) in rat ventricular tissue. Aromatin E, F, and J showed moderate activities with an increase in cAMP levels by 67%, 69%, and 64%, respectively, compared with the control group.
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http://dx.doi.org/10.1016/j.phytochem.2021.112659DOI Listing
April 2021

Oligosaccharides from Polygonatum Cyrtonema Hua: Structural characterization and treatment of LPS-induced peritonitis in mice.

Carbohydr Polym 2021 Mar 10;255:117392. Epub 2020 Nov 10.

State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China; Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China. Electronic address:

Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) for the first time. Structure characterized using FT-IR, MALDI-TOF-MS, NMR, AFM, and TEM, indicated that PFOS was graminan-type fructan with a degree of polymerization ranging from 5 to 10. A murine model of lipopolysaccharide (LPS)-induced peritonitis was used to evaluate the in vivo anti-inflammatory and lung protective efficacy of PFOS. The result shown that pretreatment with PFOS (1.0 mg/mL) in peritonitis-induced mice could significantly inhibit the level of pro-inflammatory cytokines (TNF-α, IL-1β) in serum (P < 0.001), increase mice survival rate from 12.5 % to 54 % (P < 0.05), and alleviated lung injury through ameliorating the damage of the pulmonary cellular architecture and reducing inflammatory monocyte accumulation in lung tissue. This effect of oligosaccharides could explain the traditional usage of P. cyrtonema as a tonic medicine for respiratory problems and it could be used as a potential natural ingredient with anti-inflammatory activity.
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http://dx.doi.org/10.1016/j.carbpol.2020.117392DOI Listing
March 2021

Automated brain morphometric biomarkers from MRI at term predict motor development in very preterm infants.

Neuroimage Clin 2020 28;28:102475. Epub 2020 Oct 28.

Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States. Electronic address:

Very preterm infants are at high risk for motor impairments. Early interventions can improve outcomes in this cohort, but they would be most effective if clinicians could accurately identify the highest-risk infants early. A number of biomarkers for motor development exist, but currently none are sufficiently accurate for early risk-stratification. We prospectively enrolled very preterm (gestational age ≤31 weeks) infants from four level-III NICUs. Structural brain MRI was performed at term-equivalent age. We used a established pipeline to automatically derive brain volumetrics and cortical morphometrics - cortical surface area, sulcal depth, gyrification index, and inner cortical curvature - from structural MRI. We related these objective measures to Bayley-III motor scores (overall, gross, and fine) at two-years corrected age. Lasso regression identified the three best predictive biomarkers for each motor scale from our initial feature set. In multivariable regression, we assessed the independent value of these brain biomarkers, over-and-above known predictors of motor development, to predict motor scores. 75 very preterm infants had high-quality T2-weighted MRI and completed Bayley-III motor testing. All three motor scores were positively associated with regional cortical surface area and subcortical volumes and negatively associated with cortical curvature throughout the majority of brain regions. In multivariable regression modeling, thalamic volume, curvature of the temporal lobe, and curvature of the insula were significant predictors of overall motor development on the Bayley-III, independent of known predictors. Objective brain morphometric biomarkers at term show promise in predicting motor development in very preterm infants.
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http://dx.doi.org/10.1016/j.nicl.2020.102475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649646PMC
June 2021

An innovative filtration based Raman mapping technique for the size characterization of anatase titanium dioxide nanoparticles.

Talanta 2021 Mar 4;224:121836. Epub 2020 Nov 4.

Department of Food Science, University of Massachusetts, Amherst, MA, 01003, USA. Electronic address:

Characterization of titanium dioxide nanoparticles (TiO-NPs) is of significant importance in the production quality control, applications and study of their toxicological effects. In this study, we developed a filtration-based Raman mapping technique as a rapid approach for the analysis of different sizes and concentrations of anatase TiO-NPs. Four different sizes of TiO standards: 173, 93, 41, and 8 nm measured by electron microscopy techniques were dispersed using a probe sonicator with sodium pyrophosphate as a dispersing agent. The resulting hydrodynamic diameter measured by dynamic light scattering (DLS) was stabilized at 192, 289, 325, and 360 nm respectively as a negative correlation with the ones by TEM. These NPs were then collected on a 0.1 μm (pore size) filter membrane with a vacuum pump and scanned using a Raman imaging microscope. The result shows that the 100 × objective lens was more capable of detecting the smallest size particles (8 nm) and lowest concentration (0.0004 g L) evaluated than the 20 × objective lens. Moreover, at low concentrations (i.e. 0.0004 and 0.004 g L), we established a linear correlation between the map area covered by the particles and the particle size measured by TEM. While at higher concentration (i.e. 0.04 g L), a positive correlation was established between the particle size and its corresponding Raman intensity. These results demonstrated a successful application of Raman mapping technique in rapid characterization of the size of anatase TiO-NPs as small as 8 nm, which will facilaite the TiO-NPs research, production, and applications.
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http://dx.doi.org/10.1016/j.talanta.2020.121836DOI Listing
March 2021

A facile solvent extraction method facilitating surface-enhanced Raman spectroscopic detection of ochratoxin A in wine and wheat.

Talanta 2021 Mar 21;224:121792. Epub 2020 Oct 21.

Department of Food Science, University of Massachusetts, MA, Amherst, USA. Electronic address:

The capability of a solvent-mediated liquid-liquid extraction (LLE) method to improve the detection of ochratoxin A (OTA) in food matrixes using surface-enhanced Raman spectroscopy (SERS) is described. SERS detection of mycotoxins with nanoparticle aggregation is a simple method but with low reproducibility due to the heterogeneous distribution of the nanoparticle aggregates. We evaluated three different LLE protocols to analyze their performance in combination with SERS. A facile extraction method based on sample acidification and addition of chloroform as a separation solvent showed to not only extract OTA from wine and wheat but also facilitate the uniform distribution of the nanoparticles leading to an improvement of the detection signals and the reproducibility. This method enables rapid and simple analysis of mycotoxin Ochratoxin A in food systems.
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http://dx.doi.org/10.1016/j.talanta.2020.121792DOI Listing
March 2021

Correction: Prenatal opioid exposure is associated with smaller brain volumes in multiple regions.

Pediatr Res 2020 Dec 8. Epub 2020 Dec 8.

Perinatal Institute, Division of Neonatology, Cincinnati Children's Hospital, Cincinnati, OH, USA.

A Correction to this paper has been published: https://doi.org/10.1038/s41390-020-01297-2.
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http://dx.doi.org/10.1038/s41390-020-01297-2DOI Listing
December 2020

UHPLC-QTOF-MS based metabolite profiling analysis and the correlation with biological properties of wild and artificial agarwood.

J Pharm Biomed Anal 2021 Feb 20;194:113782. Epub 2020 Nov 20.

National Engineering Institute for the Research and Development of Endangered Medicinal Resources in Southwest China, Guangxi Botanical Garden of Medicinal Plants, Nanning, 530023, China. Electronic address:

To date, the agarwood has been over exploited worldwide in the wild due to high demand. As an alternative, the agarwood obtained through artificial methods has greatly resolved the shortage of agarwood supply in the global market. However, little information about the difference in chemical constituents and bioactivities of the wild agarwood and the artificial agarwood is available. This study aims to systematically compare the chemical composition and the bioactivities between wild and artificial agarwood on the basis of the integrated method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF-MS) and multivariate statistical analysis. The invitro antioxidant activity was determined using the 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) radical scavenging activity assays. The cytotoxic activity of agarwood from different origin against three human cancer cell lines (i.e., A375, U251, and Skov3) were compared using the MTT assay. Fifty metabolites from UPLC-QTOF-MS spectra were identified and included in the multivariate analysis. Among these metabolites, 2-(2-phenylethyl) chromone derivatives (PECs), bi-2-(2-phenylethyl) chromone derivatives (BPECs) and sesquiterpene-2-(2-phenylethyl) chromone conjugates (SPECs) were found to be the major metabolites and acted as discriminant compounds in agarwood from different origin. The antioxidant activity study showed that the wild agarwood displayed significant antioxidant capacity compared with the artificial agarwood. Particularly, the content of secondary metabolites of SPEC analogs shown a positive effect on the radical scavenging activities, whereas the PECs were negatively correlated. Interestingly, no significant difference was observed between wild and artificial agarwood in terms of cytotoxic activity against three human cancer cell lines (i.e., A375, U251, and Skov3). To the best of our knowledge, this research is the first to study the metabolite profiles and bioactivities of the wild and the artificial agarwood in a holistic approach, and is expected to provide a rational basis for the quality assessment of artificial agarwood as a substitute for wild agarwood.
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http://dx.doi.org/10.1016/j.jpba.2020.113782DOI Listing
February 2021

Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age Magnetic Resonance Imaging in Infants Born Very Preterm.

J Pediatr 2021 Jun 28;233:58-65.e3. Epub 2020 Nov 28.

The Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Objective: To identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm.

Study Design: A prospective cohort of 392 infants born very preterm (≤32 weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45 weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA.

Results: Of the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (P = .027), severe bronchopulmonary dysplasia (BPD) (P = .009), severe retinopathy of prematurity (P < .001), and male sex (P = .041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P = .004), duration of caffeine therapy for severe BPD (P = .009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P = .049).

Conclusions: Severe retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.
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http://dx.doi.org/10.1016/j.jpeds.2020.11.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290900PMC
June 2021

Headspace Characterization and Quantification of Aromatic Organosulfur Compounds in Garlic Extracts Using Surface-Enhanced Raman Scattering with a Mirror-in-a-Cap Substrate.

J AOAC Int 2020 Sep;103(5):1201-1207

University of Massachusetts, Department of Food Science, Amherst, MA 01002, USA.

Background: Surface-enhanced Raman scattering (SERS) has been deployed in the analysis of food at solid and aqueous states. However, its capability has not been fully explored in headspace profiling.

Objective: To develop an innovative SERS method for analyzing headspace volatile compounds in foods.

Methods: A volatile-capture device was developed by depositing a film of silver nanoparticles in a vial cap to capture the volatiles released from a model flavor compound (garlic).

Results: SERS peaks at 1632, 1400, 1291, 1191, 731, and 577 cm-1 were identified in the headspace of the garlic sample, which was representative of an organosulfur compound (diallyl disulfide), and its concentration was determined at 135 ppm, which was comparable to the value determined using GC. Preparation and analysis could be carried out in <10 min for the SERS method. The sensitivity of the SERS method (10 ppm), however, was slightly less than that of the GC method (5 pm).

Conclusions: The SERS method was able to quantify the concentration of diallyl disulfide in the headspace of a raw garlic ethanolic extract. Compared to GC, the SERS method had a much shorter analysis time and simpler sample preparation procedure than GC when analyzing large numbers of samples.

Highlights: The innovative "mirror-in-a-cap" substrate was simpler and faster than other reported SERS substrates used for this purpose. Additionally, SERS has much better portability and the potential for real-time monitoring of changes in the garlic headspace concentration during manufacturing and processing.
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http://dx.doi.org/10.1093/jaoacint/qsaa021DOI Listing
September 2020

Digestion of animal- and plant-based proteins encapsulated in κ-carrageenan/protein beads under simulated gastrointestinal conditions.

Food Res Int 2020 11 18;137:109662. Epub 2020 Sep 18.

Food Science Department, University of Massachusetts Amherst, Amherst, MA, USA. Electronic address:

In this study, we encapsulated both animal-derived (whey) and plant-derived (soy and pea) proteins within polysaccharide/protein beads and measured the digestion of these beads under simulated gastrointestinal tract (GIT) conditions. Bead dimensions were measured using a digital caliper and found to increase as the shear thinning behavior of the protein/polysaccharide solutions used to form them increased. The hydrolysis of the plant and animal proteins trapped inside the protein/polysaccharide beads was studied using the pH-stat automatic titration method under simulated static GIT conditions. The encapsulated proteins were relatively resistant to digestion under gastric conditions, with only about 10 to 13% of the protein being digested by the end of the stomach phase. Conversely, they were almost fully digested under small intestinal conditions, with around 87 to 97% of the protein being hydrolyzed by the end. Indeed, by the completion of the small intestine phase, only "ghost" beads remained that contained cross-linked polysaccharides. The soy and pea proteins were digested slightly faster than the whey proteins in the stomach phase (p < 0.05), whereas the pea proteins were digested slightly faster than the soy and whey proteins under intestinal conditions (p < 0.05). Raman spectroscopy and scanning electron microscopy showed that there were changes in the composition and structure of the beads throughout the simulated GIT. Our results indicate that the gastrointestinal behavior of proteins can be modulated by encapsulating them in polysaccharide beads, which may be useful for the design of certain types of functional foods. Even so, the beads formed from the plant-based and animal-based proteins behaved fairly similarly, suggesting that animal proteins could be replaced by plant-based ones for this purpose.
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http://dx.doi.org/10.1016/j.foodres.2020.109662DOI Listing
November 2020

Prenatal opioid exposure is associated with smaller brain volumes in multiple regions.

Pediatr Res 2020 Nov 11. Epub 2020 Nov 11.

Perinatal Institute, Division of Neonatology, Cincinnati Children's Hospital, Cincinnati, OH, USA.

Background: The impact of prenatal opioid exposure on brain development remains poorly understood.

Methods: We conducted a prospective study of term-born infants with and without prenatal opioid exposure. Structural brain MRI was performed between 40 and 48 weeks postmenstrual age. T2-weighted images were processed using the Developing Human Connectome Project structural pipeline. We compared 63 relative regional brain volumes between groups.

Results: Twenty-nine infants with prenatal opioid exposure and 42 unexposed controls were included. The groups had similar demographics, except exposed infants had lower birth weights, more maternal smoking and maternal Hepatitis C, fewer mothers with a college degree, and were more likely non-Hispanic White. After controlling for sex, postmenstrual age at scan, birth weight, and maternal education, exposed infants had significantly smaller relative volumes of the deep gray matter, bilateral thalamic ventrolateral nuclei, bilateral insular white matter, bilateral subthalamic nuclei, brainstem, and cerebrospinal fluid. Exposed infants had larger relative volumes of the right cingulate gyrus white matter and left occipital lobe white matter.

Conclusions: Infants with prenatal opioid exposure had smaller brain volumes in multiple regions compared to controls, with two regions larger in the opioid-exposed group. Further research should focus on the relative contributions of maternal opioids and other exposures.

Impact: Prenatal opioid exposure is associated with developmental and behavioral consequences, but the direct effects of opioids on the developing human brain are poorly understood. Prior small studies using MRI have shown smaller regional brain volumes in opioid-exposed infants and children. After controlling for covariates, infants with prenatal opioid exposure scanned at 40-48 weeks postmenstrual age had smaller brain volumes in multiple regions compared to controls, with two regions larger in the opioid-exposed group. This adds to the literature showing potential impact of prenatal opioid exposure on the developing brain.
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http://dx.doi.org/10.1038/s41390-020-01265-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110593PMC
November 2020

miR-660-5p promotes breast cancer progression through down-regulating TET2 and activating PI3K/AKT/mTOR signaling.

Braz J Med Biol Res 2020 30;53(12):e9740. Epub 2020 Oct 30.

Department of General Surgery, The Second People's Hospital of Jingmen, Jingmen, Hubei, China.

Breast cancer (BC) is a commonly diagnosed cancer in females. MicroRNA-660-5p (miR-660-5p) has been reported to be involved in the occurrence and development of BC. However, the regulatory network of miR-660-5p in BC has not been fully addressed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the enrichment of miR-660-5p and tet-eleven translocation 2 (TET2) in BC tissues and cells. Cell counting kit-8 (CCK8), flow cytometry, and transwell migration and invasion assays were used to measure cell proliferation, apoptosis, migration, and invasion. The target relationship between miR-660-5p and TET2 was confirmed by dual luciferase reporter assay. Protein expression was measured by western blot. The expression of miR-660-5p was elevated in BC, and high expression of miR-660-5p was closely related to lymph node metastasis, advanced TNM stage, and vascular invasion of BC tumors. miR-660-5p silencing inhibited cell proliferation and metastasis, but induced apoptosis of BC cells. TET2 was identified as a direct target of miR-660-5p, and the interference of TET2 partly reversed the suppressive effects of miR-660-5p silencing on the malignant potential of BC cells. miR-660-5p promoted BC progression partly through modulating TET2 and PI3K/AKT/mTOR signaling. miR-660-5p/TET2 axis might be a promising target for BC treatment.
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http://dx.doi.org/10.1590/1414-431X20209740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643928PMC
January 2021