Publications by authors named "Cheng Tong"

152 Publications

Biocatalyst and colorimetric biosensor of carcinoembryonic antigen constructed via chicken egg white-copper phosphate organic/inorganic hybrid nanoflowers.

J Colloid Interface Sci 2021 May 18;601:50-59. Epub 2021 May 18.

School of Materials Science and Engineering, Shaanxi Key Laboratory of Green Preparation and Functionalization for Inorganic Materials, Shaanxi University of Science and Technology, Xi'an 710021, PR China.

In this article, the dual-functional chicken egg white-copper phosphate organic-inorganic hybrid nanoflowers (Cu-NFs), combining the functions of signal amplification and biological recognition, were prepared through a simple one-pot method. The Cu-NFs exhibit excellent biocatalytic activity of peroxidase and polyphenol oxidase. Besides, a biotin-labeled secondary antibody encapsulated Cu-NFs-2 ([email protected]) capture probe was prepared by using the interaction between avidin in the egg white and biotin. Based upon this superiority, the as-prepared Cu-NFs-2 were used in labeled avidin-biotin enzyme-linked immunosorbent assay (Cu-NFs-2 based-LAB-ELISA) to construct a sensitive colorimetric biosensor for the ultrasensitive detection of carcinoembryonic antigen (CEA). Under weak alkaline (pH = 7.5) conditions, the as-developed colorimetric sensor displayed a wide linear range of 0.05-40 ng/mL with a detection limit of 3.52 pg/mL. Furthermore, this colorimetric sensor has been successfully applied to the detection of CEA in human serum samples. Therefore, the as-developed colorimetric sensor has broad application prospects in the field of medical diagnosis and portable detection.
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http://dx.doi.org/10.1016/j.jcis.2021.05.069DOI Listing
May 2021

A SCID mouse-human lung xenograft model of SARS-CoV-2 infection.

Theranostics 2021 3;11(13):6607-6615. Epub 2021 May 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection . Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
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http://dx.doi.org/10.7150/thno.58321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120224PMC
May 2021

A novel nonenzymatic ascorbic acid electrochemical sensor based on gold nanoparticals-chicken egg white-copper phosphate-graphene oxide hybrid nanoflowers.

Nanotechnology 2021 May 21;32(32). Epub 2021 May 21.

School of Materials Science and Engineering, Shaanxi Key Laboratory of Green Preparation and Functionalization for Inorganic Materials, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.

Au-CEW-Cu(PO)-GO nanoflowers (HNFs), which were assembled of gold nanoparticals (Au NPs), chicken egg white (CEW), copper phosphate (Cu(PO)) and graphene oxide (GO) together to form a flower-like organic/inorganic hybrid nanocomposite, were synthesized through a simple and gentle one-pot co-precipitation method. The prepared samples were well characterized by scanning electron microscope, transmission electron microscope, energy dispersive x-ray spectrometer, x-ray diffraction and Raman spectrometer. The prepared Au-CEW-Cu(PO)-GO HNFs was used to modify glassy carbon electrode to fabricate an electrochemical sensor for detection of ascorbic acid (AA). The electrochemical test results show that the linear range of the developed sensor is 8-300M and the detection limit is 2.67M (S/N = 3). While this sensor displays high sensitivity of 6.01 × 10AMcmand low detection potential of 35 mV due to the combination of the high conductivity of Au NPs, the larger specific surface area of GO and the intrinsic electrocatalytic activity of CEW-Cu(PO)HNFs. Moreover, the Au-CEW-Cu(PO)-GO HNFs-based sensor was successfully developed for application in electrochemical detection of AA in vitamin C tablets.
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http://dx.doi.org/10.1088/1361-6528/abfe28DOI Listing
May 2021

How Mother-Child Interactions are Associated with a Child's Compliance.

Cereb Cortex 2021 Apr 24. Epub 2021 Apr 24.

State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, P.R. China.

While social interaction between a mother and her child has been found to play an important role in the child's committed compliance, the underlying neurocognitive process remains unclear. To investigate this process, we simultaneously recorded and assessed brain activity in 7-year-old children and in children's mothers or strangers during a free-play task using functional near-infrared spectroscopy-based hyperscanning. The results showed that a child's committed compliance was positively associated with the child's responsiveness but was negatively associated with mutual responsiveness and was not associated with the mother's responsiveness during mother-child interactions. Moreover, interpersonal neural synchronization (INS) at the temporoparietal junction mediated the relationship between the child's responsiveness and the child's committed compliance during mother-child interactions when the child's brain activity lagged behind that of the mother. However, these effects were not found during stranger-child interactions, nor were there significant effects in the mother-child pair when no real interactions occurred. Finally, we found a transfer effect of a child's committed compliance from mother-child interactions to stranger-child interactions via the mediation of mother-child INS, but the opposite did not occur. Together, these findings suggest that a child's responsiveness during mother-child interactions can significantly facilitate her or his committed compliance by increasing mother-child INS.
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http://dx.doi.org/10.1093/cercor/bhab094DOI Listing
April 2021

A transcriptional regulatory module controls lipid accumulation in soybean.

New Phytol 2021 07 25;231(2):661-678. Epub 2021 May 25.

State Key Lab of Plant Genomics, Institute of Genetics and Developmental Biology, INASEED, Chinese Academy of Sciences, Beijing, 100101, China.

Soybean (Glycine max) is one of the most important oilseed crops. However, the regulatory mechanism that governs the process of oil accumulation in soybean remains poorly understood. In this study, GmZF392, a tandem CCCH zinc finger (TZF) protein which was identified in our previous RNA-seq analysis of seed-preferred transcription factors, was found to function as a positive regulator of lipid production. GmZF392 promotes seed oil accumulation in both transgenic Arabidopsis and stable transgenic soybean plants by binding to a bipartite cis-element, containing TG- and TA-rich sequences, in promoter regions, activating the expression of genes in the lipid biosynthesis pathway. GmZF392 physically interacts with GmZF351, our previously identified transcriptional regulator of lipid biosynthesis, to synergistically promote downstream gene expression. Both GmZF392 and GmZF351 are further upregulated by GmNFYA, another transcription factor involved in lipid biosynthesis, directly (in the former case) and indirectly (in the latter case). Promoter sequence diversity analysis showed that the GmZF392 promoter may have been selected at the origin of the Glycine genus and further mildly selected during domestication from wild soybeans to cultivated soybeans. Our study reveals a regulatory module containing three transcription factors in the lipid biosynthesis pathway, and manipulation of the module may improve oil production in soybean and other oilseed crops.
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http://dx.doi.org/10.1111/nph.17401DOI Listing
July 2021

In Response to Assessing the Performance of the Shikani Optical Stylet for Awake Nasal Intubation.

Laryngoscope 2021 07 13;131(7):E2276. Epub 2021 Apr 13.

Department of Anesthesiology, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.

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http://dx.doi.org/10.1002/lary.29567DOI Listing
July 2021

Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster.

Signal Transduct Target Ther 2021 03 31;6(1):136. Epub 2021 Mar 31.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, P. R. China.

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.
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http://dx.doi.org/10.1038/s41392-021-00552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009924PMC
March 2021

The prevalence of antibodies to SARS-CoV-2 among blood donors in China.

Nat Commun 2021 03 2;12(1):1383. Epub 2021 Mar 2.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.

In this study, we investigate the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China. From January to April 2020, 38,144 healthy blood donors in the three cities were tested for total antibody against SARS-CoV-2 followed by pseudotype SARS-CoV-2 neutralization tests, IgG, and IgM antibody testing. Finally, a total of 398 donors were confirmed positive. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18-60 year-old adults (18-65 year-old in Shenzhen) was 2.66% (95% CI: 2.24%-3.07%) in Wuhan, 0.033% (95% CI: 0.0029%-0.267%) in Shenzhen, and 0.0028% (95% CI: 0.0001%-0.158%) in Shijiazhuang, respectively. Female sex and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among blood donors in Wuhan. As most of the population of China remained uninfected during the early wave of the COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.
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http://dx.doi.org/10.1038/s41467-021-21503-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925561PMC
March 2021

Virus-Free and Live-Cell Visualizing SARS-CoV-2 Cell Entry for Studies of Neutralizing Antibodies and Compound Inhibitors.

Small Methods 2021 Feb 18;5(2):2001031. Epub 2020 Dec 18.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public Health & School of Life Sciences Xiamen University Xiamen Fujian 361102 China.

The ongoing corona virus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, a genetically engineered sensor of fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process is developed. In ACE2-expressing cells, it is found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.
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http://dx.doi.org/10.1002/smtd.202001031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883248PMC
February 2021

Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.

Cell Host Microbe 2021 03 3;29(3):448-462.e5. Epub 2021 Feb 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China; Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, Xiamen, Fujian 361102, China. Electronic address:

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.
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http://dx.doi.org/10.1016/j.chom.2021.01.001DOI Listing
March 2021

Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids.

Nat Microbiol 2020 12 7;5(12):1542-1552. Epub 2020 Sep 7.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China.

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP-the largest among human herpesviruses-uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.
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http://dx.doi.org/10.1038/s41564-020-0785-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677223PMC
December 2020

A uniform quantitative enzyme-linked immunosorbent assay for Coxsackievirus A16 antigen in vaccine.

Hum Vaccin Immunother 2021 02 4;17(2):381-388. Epub 2020 Aug 4.

Divison of Hepatitis Virus and Enterovirus Vaccine, National Institutes for Food and Drug Control, Institute for Biological Product Control , Beijing, China.

Coxsackievirus A16 (CV-A16), one of major etiological agents of hand, foot and mouth disease (HFMD), causes outbreaks of the disease in young children all over the world. In order to promote the prevention and control of HFMD, the research and development of CV-A16 vaccine have been carried out in China. However, due to lacking of a recognized CV-A16 antigen detection method, the evaluation and quality control (QC) of vaccine effectiveness are greatly limited. In this study, we established a quantitative enzyme-linked immunosorbent assay (Q-ELISA) to determine the antigen concentration in CV-A16 vaccines that can be applied in manufacturing in China. A neutralizing antibody 16E1 was used as a capture antibody that can bind to various CV-A16 antigens of different subgenotypes, and an antiserum from CV-A16-immunized rabbit conjugated by HRP was suitable for detecting and quantifying CV-A16 antigens. The Q-ELISA was validated for specificity, linearity, accuracy, precision and robustness by using the CV-A16 antigen national standard (NS). Furthermore, we utilized the Q-ELISA to quantify antigen contents of vaccine bulks from six manufacturers and other intermediate products from one manufacturer. The results indicated that the Q-ELISA can satisfy the requirements of QC for all manufacturers involved.
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http://dx.doi.org/10.1080/21645515.2020.1776547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899661PMC
February 2021

Abundant and Diverse RNA Viruses in Insects Revealed by RNA-Seq Analysis: Ecological and Evolutionary Implications.

mSystems 2020 Jul 7;5(4). Epub 2020 Jul 7.

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbiology Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China

Increasing data indicate that insects serve as major reservoirs and vectors of viruses, which account for the continuously increasing ecological burden and infectious disease outbreaks. Uncovering the hidden diversity of viruses in insects will further the understanding of the ecological and evolutionary perspectives in the emergence of insect-associated virus diseases. In this study, we queried transcriptome sequencing (RNA-Seq) data from more than 600 species across 32 insect orders dwelling in different ecological habitats and recovered more than 1,213 RNA viruses that were recapitulated in 40 families, 2 unclassified genera, and many unspecified viral groups. These novel viruses included the well-known insect-associated viruses within , , , , , , and More appeared to form novel clusters within previously described taxa or could be resolved as paraphyletic, including the first astrovirus identified in insects, in which many were sufficiently divergent to warrant the establishment of new virus genera or families. Additionally, some viruses were closely related to the recognized plant-, fungus-, and vertebrate-specific species, implying the importance of relationships between insect behavior and virus spread. Comparative genome analyses also revealed high genomic variability with respect to the flexible gene pool and genome architecture of these newly described viruses, including the evidence for genome reshuffling first discovered in The data reflecting the genetically and ecologically diverse viral populations in insects greatly expand our understanding of RNA viruses in nature and highlight that the biodiversity of RNA viruses remains largely unexplored. Insects comprise the largest proportion of animals on earth and are frequently implicated in the transmission of vector-borne diseases. However, considerable attention has been paid to the phytophagous and hematophagous insects, with results that provide insufficient and biased information about the viruses in insects. Here, we have delivered compelling evidence for the exceptional abundance and genetic diversity of RNA viruses in a wide range of insects. Novel viruses were found to cover major categories of RNA viruses, and many formed novel clusters divergent from the previously described taxa, dramatically broadening the range of known RNA viruses in insects. These newly characterized RNA viruses exhibited high levels of genomic plasticity in genome size, open reading frame (ORF) number, intergenic structure, and gene rearrangement and segmentation. This work provides comprehensive insight into the origin, spread, and evolution of RNA viruses. Of course, a large-scale virome project involving more organisms would provide more-detailed information about the virus infections in insects.
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http://dx.doi.org/10.1128/mSystems.00039-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343303PMC
July 2020

DLL4 restores damaged liver by enhancing hBMSC differentiation into cholangiocytes.

Stem Cell Res 2020 Jun 29;47:101900. Epub 2020 Jun 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; Taizhou Central Hospital, Taizhou University Hospital, 999 Donghai Rd., Taizhou 318000, China. Electronic address:

Background & Aims: Biliary injury is one of the main pathological mechanisms of fulminant hepatic failure (FHF). Delta-like ligand 4 (DLL4)-mediated Notch activation contributes to reversing biliary injury; however, the specific role of DLL4 in biliary restoration is still unclear. This study aimed to determine whether human bone marrow mesenchymal stem cells (hBMSCs) can differentiate into biliary epithelial cells (cholangiocytes) in vitro and in vivo and to clarify the role of DLL4 in restoring damaged liver by enhancing cholangiocyte differentiation.

Methods: hBMSCs were transplanted into immunodeficient mice (FRGS) with FHF induced by the hamster-anti-mouse CD95 antibody JO2. The appearance of human cholangiocytes was evaluated in the generated hBMSC-FRGS mice by q-PCR expression, flow cytometry and immunohistochemistry. The potency of DLL4 in inducing cholangiocyte differentiation from hBMSCs was assessed by observing the cell morphology and measuring the expression of cholangiocyte-specific genes and proteins.

Results: Human KRT19- and KRT7-double-positive cholangiocyte-like cells appeared in hBMSC-FRGS mice at 12 weeks after transplantation. After these cells were separated and collected by fluorescent-activated cell sorting (FACS), there were high levels of expression of eight typical human cholangiocyte-specific genes and proteins (e.g., KRT19 and KRT7). Furthermore, hBMSC-derived cholangiocytes induced by DLL4 had a better shape with higher nucleus/cytoplasm ratios and showed a specific increase in the expression of cholangiocyte-specific genes and proteins (e.g., KRT19, KRT7, SOX9 and CFTR).

Conclusions: Cholangiocytes can be efficiently differentiated from hBMSCs in vivo and in vitro. DLL4 restores damaged liver by enhancing cholangiocyte differentiation from hBMSCs and has the potential to be used in future clinical therapeutic applications.
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http://dx.doi.org/10.1016/j.scr.2020.101900DOI Listing
June 2020

Genetic Analysis of 25 Patients with 5-Reductase Deficiency in Chinese Population.

Biomed Res Int 2020 9;2020:1789514. Epub 2020 Jun 9.

Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: A deficiency in steroid 5-reductase type 2 is an autosomal recessive disorder. Affected individuals manifested ambiguous genitalia, which is caused by decreased dihydrotestosterone (DHT) synthesis in the fetus.

Methods: We analyzed 25 patients with 5-reductase deficiency in China. Seventeen of the 25 patients (68%) were initially raised as females. Sixteen patients changed their social gender from female to male after puberty.

Results: Eighteen mutations were identified in these patients. p.Gly203Ser and p.Gln6∗ were found to be the most prevalent mutations. On the basis of the genotype of these patients, we divided them into different groups. There was no significant difference in hormone levels and external masculinization score (EMS) in patients with or without these prevalent mutations. Twelve common single-nucleotide polymorphisms (SNPs) near the p.Gln6∗ mutation were chosen for haplotype analysis. Three haplotypes were observed in 6 patients who had the p.Gln6∗ mutation (12 alleles).

Conclusion: We analyzed mutations of the gene in Chinese patients with 5-reductase deficiency. Although hotspot mutations exist, no founder effect of prevalent mutations in the gene was detected in the Chinese population.
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http://dx.doi.org/10.1155/2020/1789514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301183PMC
March 2021

Shikani Optical Stylet for Awake Nasal Intubation in Patients Undergoing Head and Neck Surgery.

Laryngoscope 2021 02 10;131(2):319-325. Epub 2020 Jun 10.

Department of Anesthesiology, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.

Objectives: To evaluate the efficacy and safety of the Shikani optical stylet (SOS) versus fiberoptic bronchoscope (FOB) for awake nasal intubation in head and neck surgery patients with an anticipated difficult airway.

Study Design: Prospective randomized clinical trial.

Methods: This study involved 50 adult patients scheduled for elective head and neck surgery and presented with an anticipated difficult airway. Patients planned for awake nasotracheal intubation were randomly divided into two groups: FOB (n = 25) and SOS (n = 25). Patients were intubated under local anesthesia and sedation using the randomly assigned intubation device by anesthetists proficient in both airway devices. The time to successful intubation was regarded as the primary endpoint.

Results: The median time (interquartile range) to tracheal intubation in the FOB group was 74 seconds (57-108) and 38 seconds (27-60) in the SOS group (P < .001). Intubation success rates on the first attempt in the FOB and SOS groups were 96% and 92%, respectively (P > .999). Airway assisted maneuvers were required in six (24%) SOS intubations compared to 21 (84%) FOB intubations (P < .001). There were no significant differences between the groups in the incidences of oxygen desaturation and postoperative complications related to intubation.

Conclusion: Compared to the FOB group, awake nasal intubation in the SOS group required significantly less time and fewer airway-assisted maneuvers on adult head and neck surgery patients with anticipated difficult airway.

Level Of Evidence: 2 Laryngoscope, 131:319-325, 2021.
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http://dx.doi.org/10.1002/lary.28763DOI Listing
February 2021

Novel visualized quantitative epigenetic imprinted gene biomarkers diagnose the malignancy of ten cancer types.

Clin Epigenetics 2020 05 24;12(1):71. Epub 2020 May 24.

Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Background: Epigenetic alterations are involved in most cancers, but its application in cancer diagnosis is still limited. More practical and intuitive methods to detect the aberrant expressions from clinical samples using highly sensitive biomarkers are needed. In this study, we developed a novel approach in identifying, visualizing, and quantifying the biallelic and multiallelic expressions of an imprinted gene panel associated with cancer status. We evaluated the normal and aberrant expressions measured using the imprinted gene panel to formulate diagnostic models which could accurately distinguish the imprinting differences of normal and benign cases from cancerous tissues for each of the ten cancer types.

Results: The Quantitative Chromogenic Imprinted Gene In Situ Hybridization (QCIGISH) method developed from a 1013-case study which provides a visual and quantitative analysis of non-coding RNA allelic expressions identified the guanine nucleotide-binding protein, alpha-stimulating complex locus (GNAS), growth factor receptor-bound protein (GRB10), and small nuclear ribonucleoprotein polypeptide N (SNRPN) out of five tested imprinted genes as efficient epigenetic biomarkers for the early-stage detection of ten cancer types. A binary algorithm developed for cancer diagnosis showed that elevated biallelic expression (BAE), multiallelic expression (MAE), and total expression (TE) measurements for the imprinted gene panel were associated with cell carcinogenesis, with the formulated diagnostic models achieving consistently high sensitivities (91-98%) and specificities (86-98%) across the different cancer types.

Conclusions: The QCIGISH method provides an innovative way to visually assess and quantitatively analyze individual cells for cancer potential extending from hyperplasia and dysplasia until carcinoma in situ and invasion, which effectively supplements standard clinical cytologic and histopathologic diagnosis for early cancer detection. In addition, the diagnostic models developed from the BAE, MAE, and TE measurements of the imprinted gene panel GNAS, GRB10, and SNRPN could provide important predictive information which are useful in early-stage cancer detection and personalized cancer management.
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http://dx.doi.org/10.1186/s13148-020-00861-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245932PMC
May 2020

Animal models for emerging coronavirus: progress and new insights.

Emerg Microbes Infect 2020 Dec;9(1):949-961

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, PR People's Republic of China.

The emergences of coronaviruses have caused a serious global public health problem because their infection in humans caused the severe acute respiratory disease and deaths. The outbreaks of lethal coronaviruses have taken place for three times within recent two decades (SARS-CoV in 2002, MERS-CoV in 2012 and SARS-CoV-2 in 2019). Much more serious than SARS-CoV in 2002, the current SARS-CoV-2 infection has been spreading to more than 213 countries, areas or territories and causing more than two million cases up to date (17 April 2020). Unfortunately, no vaccine and specific anti-coronavirus drugs are available at present time. Current clinical treatment at hand is inadequate to suppress viral replication and inflammation, and reverse organ failure. Intensive research efforts have focused on increasing our understanding of viral biology of SARS-CoV-2, improving antiviral therapy and vaccination strategies. The animal models are important for both the fundamental research and drug discovery of coronavirus. This review aims to summarize the animal models currently available for SARS-CoV and MERS-CoV, and their potential use for the study of SARS-CoV-2. We will discuss the benefits and caveats of these animal models and present critical findings that might guide the fundamental studies and urgent treatment of SARS-CoV-2-caused diseases.
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http://dx.doi.org/10.1080/22221751.2020.1764871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269044PMC
December 2020

Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16.

Cell Host Microbe 2020 02 5;27(2):249-261.e5. Epub 2020 Feb 5.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China. Electronic address:

Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens.
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http://dx.doi.org/10.1016/j.chom.2020.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539366PMC
February 2020

Systematic molecular profiling of inhibitor response to the clinical missense mutations of ErbB family kinases in human gastric cancer.

J Mol Graph Model 2020 05 26;96:107526. Epub 2019 Dec 26.

Department of Gynaecology and Obstetrics, The People's Hospital of Kunshan, Kunshan, 215300, China. Electronic address:

The oncogenic receptor tyrosine kinase family ErbB consists of four members (ErbB1, ErbB2, ErbB3 and ErbB4); they are involved in the tumorgenesis of diverse cancers. A variety of missence mutations have been clinically observed in ErbB kinases, which would shift drug sensitivity to these kinases and cause drug resistance in targeted cancer therapy. In this study, systematic inhibitor response to ErbB missense mutations in gastric cancer (GC) is investigated by combining computational analysis and experimental assay. The response profile is created for 6 ATP-competitive, reversible inhibitors against 9, 17, 5 and 17 GC-associated missense mutations of ErbB1, ErbB2, ErbB3 and ErbB4 kinase domains, respectively. From the profile a number of potential resistant and sensitive responses are identified theoretically. It is suggested that most ErbB mutations have only a modest effect on inhibitor binding, but few that are located around the kinase active site can influence the binding significantly. Structural examination reveals that steric hindrance and allosteric effect are primarily responsible for inhibitor resistance and sensitivity, respectively. Two ErbB2 mutations, namely V777L and T862A, are predicted to cause effective resistance on inhibitors TAK285 and Lapatinib, respectively. Kinase assays consistently observe that the mutations can reduce inhibitor activity by 4.9-fold and 2.4-fold, with IC changing from 29 to 16 nM (wild type) to 83 and 39 nM (mutant) for TAK285 and Lapatinib, respectively.
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http://dx.doi.org/10.1016/j.jmgm.2019.107526DOI Listing
May 2020

Rapid Neutralization Testing System for Zika Virus Based on an Enzyme-Linked Immunospot Assay.

ACS Infect Dis 2020 05 30;6(5):811-819. Epub 2019 Dec 30.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, Fujian 361102, PR China.

Zika virus (ZIKV) is a mosquito-borne flavivirus that has been associated with neuropathology in fetuses and adults, imposing a serious health concern. Therefore, the development of a vaccine is a global health priority. Notably, neutralization tests have a significant value for vaccine development and virus diagnosis. The cytopathic effect (CPE)-based neutralization test (Nt-CPE) is a common neutralization method for ZIKV. However, this method has some drawbacks, such as being time-consuming and labor-intensive and having low-throughput, which precludes its application in the detection of large numbers of specimens. To improve this problem, we developed a neutralization test based on an enzyme-linked immunospot assay (Nt-ELISPOT) for ZIKV and performed the assay in a 96-well format. A monoclonal antibody (mAb), 11C11, with high affinity and reactivity to ZIKV was used to detect ZIKV-infected cells. To optimize this method, the infectious dose of ZIKV was set at a multiplicity of infection (MOI) of 0.0625, and a detection experiment was performed after incubating for 24 h. As a result, under these conditions, the Nt-ELISPOT had good consistency with the traditional Nt-CPE to measure neutralizing titers of sera and neutralizing antibodies. Additionally, three neutralizing antibodies against ZIKV were screened by this method. Overall, we successfully developed an efficient neutralization test for ZIKV that is high-throughput and rapid. This Nt-ELISPOT can potentially be applied to detecting neutralizing titers of large numbers of specimens in vaccine evaluation and neutralizing antibody screening for ZIKV.
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http://dx.doi.org/10.1021/acsinfecdis.9b00333DOI Listing
May 2020

The Analogs of Temporin-GHa Exhibit a Broader Spectrum of Antimicrobial Activity and a Stronger Antibiofilm Potential against .

Molecules 2019 Nov 18;24(22). Epub 2019 Nov 18.

Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China.

The abuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which is becoming a serious worldwide problem people have to face. In our previous study, temporin-GHa (GHa) cloned from showed antimicrobial activity against Gram-positive bacteria. In order to improve its therapeutic potential, we used a template-based and a database-assisted design to obtain three derived peptides by replacing the histidine at both ends of GHa with lysine, which exhibited faster and stronger bactericidal activity and a broader spectrum than the parent peptide. GHaK and GHa4K targeted to the bacterial membrane to exert their antibacterial activities at a faster membrane damage rate. The derived peptides inhibited the initial adhesion and the formation of biofilms, and eradicated the mature biofilms, which indicated that the derived peptides effectively penetrated the biofilm and killed bacteria. The therapeutic index (TI) and cell selectivity index (CSI) of the derived peptides increased significantly, which means a broader therapeutic window of the derived peptides. The derived peptides with improved activity and cell selectivity have the potential to be the promising candidates for the treatment of infections. Our research also provides new insights into the design and development of antimicrobial peptides.
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http://dx.doi.org/10.3390/molecules24224173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891419PMC
November 2019

Synthesis of ammonia via electrochemical nitrogen reduction on high-index faceted Au nanoparticles with a high faradaic efficiency.

Chem Commun (Camb) 2019 Nov;55(96):14482-14485

National-municipal Joint Engineering Laboratory for Chemical Process Intensification and Reaction, College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400044, China.

The electrochemical nitrogen reduction reaction (NRR) is a promising but extremely challenging approach for ammonia synthesis under ambient conditions. Herein, we report the excellent NRR performance of gold nanoparticles (AuNPs) with multiple high-index facets, prepared by a modified seed-mediated method. At -0.3 V vs. RHE and in 0.1 M Li2SO4 aqueous solution, the AuNPs afford the highest faradaic efficiency (FE) of 73.32% reported so far, with a remarkable ammonia generation rate of 9.22 μg h-1 cm-2. Density functional theory (DFT) calculations reveal that the high-index faceted surfaces of the AuNPs have greater preference for the adsorption of NRR intermediates (*NNH) and significantly hinder the adsorption of competing hydrogen evolution intermediates (*H).
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http://dx.doi.org/10.1039/c9cc06132kDOI Listing
November 2019

A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells.

Nat Commun 2019 09 6;10(1):4066. Epub 2019 Sep 6.

Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Translational Medicine, First Hospital, Jilin University, Changchun, Jilin, 130021, China.

Human enteroviruses (HEVs) of the family Picornaviridae, which comprises non-enveloped RNA viruses, are ubiquitous worldwide. The majority of EV proteins are derived from viral polyproteins encoded by a single open reading frame (ORF). Here, we characterize a second ORF in HEVs that is crucial for viral intestinal infection. Disruption of ORF2p expression decreases the replication capacity of EV-A71 in human intestinal epithelial cells (IECs). Ectopic expression of ORF2p proteins derived from diverse enteric enteroviruses sensitizes intestinal cells to the replication of ORF2p-defective EV-A71 and respiratory enterovirus EV-D68. We show that the highly conserved WIGHPV domain of ORF2p is important for ORF2p-dependent viral intestinal infection. ORF2p expression is required for EV-A71 particle release from IECs and can support productive EV-D68 infection in IECs by facilitating virus release. Our results indicate that ORF2p is a determining factor for enteric enterovirus replication in IECs.
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http://dx.doi.org/10.1038/s41467-019-12040-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731315PMC
September 2019

Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy.

Brain Behav Immun 2019 11 19;82:178-187. Epub 2019 Aug 19.

Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, PR China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, PR China; Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macau Greater Bay Area, Guangzhou, PR China. Electronic address:

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.
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http://dx.doi.org/10.1016/j.bbi.2019.08.184DOI Listing
November 2019

Somatic mosaicism of androgen receptor gene in an androgen insensitivity syndrome patient conceived through assisted reproduction technique.

Mol Genet Genomic Med 2019 10 20;7(10):e00906. Epub 2019 Aug 20.

Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Mutations of human androgen receptor (AR) gene are responsible for androgen insensitivity syndrome (AIS). Variable phenotypes and androgen receptor binding activity have permitted the classification of AIS into complete (CAIS), partial (PAIS), and minimal or mild (MAIS) forms. Somatic mosaicism in AIS is a rare condition which happened when de novo mutations occur after the zygotic stage.

Methods: Clinical evaluation, hormone measurements, and molecular analysis were performed to diagnose the patient in the study.

Results: A 46, XY girl who conceived through in vitro fertilization (IVF), presented with partial virilization of external genitalia, was found to have the p.C620R in heterozygosity. The variant p.C620R of AR has been previously reported in a patient with completely feminized external genitalia, which was inherited from the heterozygote carrier mother. Mutation analysis of the mother of our patient revealed that the variant was de novo and presented as a somatic mosaicism which indicated an insufficient amount of wild-type AR in our patient.

Conclusion: This is the first case that AIS was caused by de novo mutation of AR in a 46, XY Disorder of Sexual Development (DSD) patient by the assisted reproduction technique (ART). The phenotype of partial virilization could be explained by AR mutation in somatic mosaicism.
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http://dx.doi.org/10.1002/mgg3.906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785456PMC
October 2019

Grade 3 Echocardiographic Diastolic Dysfunction Is Associated With Increased Risk of Major Adverse Cardiovascular Events After Surgery: A Retrospective Cohort Study.

Anesth Analg 2019 09;129(3):651-658

Biostatistics, Peking University First Hospital, Beijing, China.

Background: Diastolic dysfunction is common and may increase the risk of cardiovascular complications. This study investigated the hypothesis that, in patients with isolated left ventricular diastolic dysfunction, higher grade diastolic dysfunction was associated with greater risk of major adverse cardiovascular events (MACEs) after surgery.

Methods: This was a retrospective cohort study. Data of adult patients with isolated echocardiographic diastolic dysfunction (ejection fraction, ≥50%) who underwent noncardiac surgery from January 1, 2015 to December 31, 2015 were collected. The primary end point was the occurrence of postoperative MACEs during hospital stay, which included acute myocardial infarction, congestive heart failure, stroke, nonfatal cardiac arrest, and cardiac death. The association between the grade of diastolic dysfunction and the occurrence of MACEs was assessed with a multivariable logistic model.

Results: A total of 2976 patients were included in the final analysis. Of these, 297 (10.0%) developed MACEs after surgery. After correction for confounding factors, grade 3 diastolic dysfunction was associated with higher risk of postoperative MACEs (odds ratio, 1.71; 95% confidence interval, 1.28-2.27; P < .001) when compared with grades 1 and 2. Patients with grade 3 diastolic dysfunction developed more non-MACE complications when compared with grades 1 and 2 (uncorrected odds ratio, 1.44; 95% confidence interval, 1.07-1.95; P = .017).

Conclusions: In patients with isolated diastolic dysfunction undergoing noncardiac surgery, 10.0% develop MACEs during hospital stay after surgery; grade 3 diastolic dysfunction is associated with greater risk of MACEs.
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http://dx.doi.org/10.1213/ANE.0000000000003807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693928PMC
September 2019

Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling.

Cell Rep 2019 07;28(2):567-579.e4

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:

As a Ca-activated lipid scramblase and ion channel that mediates Ca influx, TMEM16F relies on both functions to facilitate extracellular vesicle generation, blood coagulation, and bone formation. How a bona fide ion channel scrambles lipids remains elusive. Our structural analyses revealed the coexistence of an intact channel pore and PIP-dependent protein conformation changes leading to membrane distortion. Correlated to the extent of membrane distortion, many tightly bound lipids are slanted. Structure-based mutagenesis studies further reveal that neutralization of some lipid-binding residues or those near membrane distortion specifically alters the onset of lipid scrambling, but not Ca influx, thus identifying features outside of channel pore that are important for lipid scrambling. Together, our studies demonstrate that membrane distortion does not require open hydrophilic grooves facing the membrane interior and provide further evidence to suggest separate pathways for lipid scrambling and ion permeation.
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http://dx.doi.org/10.1016/j.celrep.2019.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684876PMC
July 2019

Evaluation of ESA Active, Passive and Combined Soil Moisture Products Using Upscaled Ground Measurements.

Sensors (Basel) 2019 Jun 17;19(12). Epub 2019 Jun 17.

Natural Resources Service Center, Dalian 116021, China.

The European Space Agency (ESA) Climate Change Initiative (CCI) project combines multi-sensors at different microwave frequencies to derive three harmonized soil moisture products using active, passive and combined approaches. These long-term soil moisture products assist in understanding the global water and carbon cycles. However, extensive validations are a prerequisite before applying the retrieved soil moisture into climatic or hydrological models. To fulfill this objective, we assess the performances of three CCI soil moisture products (active, passive and combined) with respect to soil moisture networks located in China, Spain and Canada. In order to compensate the scale differences between ground stations and the CCI product's coarse resolution, we adopted two upscaling approaches of Inverse Distance Weighting (IDW) interpolation and simple Arithmetic Mean (AM). The temporal agreements between the satellite retrieved and ground-measured soil moisture were quantified using the unbiased root mean square error (ubRMSE), RMSE, correlation coefficients (R) and bias. Furthermore, the temporal variability of the CCI soil moisture is interpreted and verified with respect to the Tropical Rainfall Measuring Mission (TRMM) precipitation observations. The results show that the temporal variations of CCI soil moisture agreed with the ground measurements and the precipitation observations over the China and Spain test sites. In contrast, a significant overestimation was observed over the Canada test sites, which may be due to the strong heterogeneity in soil and vegetation characteristics in accordance with the reported poor performance of soil moisture retrieval there. However, despite a retrieval bias, the relatively temporal variation of the CCI soil moisture also followed the ground measurements. For all the three test sites, the soil moisture retrieved from the combined approach outperformed the active-only and passive-only methods, with ubRMSE of 0.034, 0.050, and 0.050-0.054 m/m over the test sites in China, Spain and Canada, respectively. Thus, the CCI combined soil moisture product is suggested to drive the climatic and hydrological studies.
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http://dx.doi.org/10.3390/s19122718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632010PMC
June 2019