Publications by authors named "Guoping Zhao"

252 Publications

Protective effect of 18β-glycyrrhetinic acid against HO-induced injury in Schwann cells based on network pharmacology and experimental validation.

Exp Ther Med 2021 Nov 1;22(5):1241. Epub 2021 Sep 1.

College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.

The aim of the present study was to assess the protective effects of 18β-GA against hydrogen peroxide (HO)-induced injury. First, the SMILES annotation for 18β-GA was used to search PubChem and for reverse molecular docking in Swiss Target Prediction, the Similarity Ensemble Approach Search Server and the TargetNet database to obtain potential targets. Injury-related molecules were obtained from the GeneCards database and the predicted targets of 18β-GA for injury treatment were selected by Wayne diagram analysis. Subsequently, Kyoto Encyclopedia of Genes and Genomes analysis was performed by WebGestalt. The experimental cells were assorted into control, model, 10 µM SB203580-treated, 5 µM 18β-GA-treated and 10 µM 18β-GA-treated groups. Hoechst 33258 staining was performed and intracellular reactive oxygen species (ROS) levels, cell apoptosis, Bcl-xl, Bcl-2, Bad, Bax, cleaved-caspase 3, cleaved-caspase 7, transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) levels, as well as p38 MAPK phosphorylation were measured. The 'Inflammatory mediator regulation of TRP channels' pathway was selected for experimental verification. The results indicated that 10 µM 18β-GA significantly increased cell viability as compared with the HO-treated model group. As suggested by the difference in intracellular ROS fluorescence intensity, 18β-GA inhibited HO-induced ROS production in Schwann cells. Hoechst 33258 staining indicated that 18β-GA reversed chromatin condensation and the increase in apoptotic nuclei following HO treatment. Furthermore, flow cytometry suggested that 18β-GA substantially inhibited HO-induced apoptosis. Pre-treatment with 18β-GA obviously reduced Bad, Bax, cleaved-caspase3, cleaved-caspase 7, TRPA1 and TRPV1 levels and p38 MAPK phosphorylation after HO treatment and increased Bcl-2 and Bcl-xl levels. In conclusion, 18β-GA inhibited Schwann cell injury and apoptosis induced by HO and may be a potential drug to prevent peripheral nerve injury.
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http://dx.doi.org/10.3892/etm.2021.10676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438673PMC
November 2021

Comparison of Fecal Collection Methods on Variation in Gut Metagenomics and Untargeted Metabolomics.

mSphere 2021 Sep 15:e0063621. Epub 2021 Sep 15.

State Key Laboratory of Genetic Engineering School of Life Sciences, Human Phenome Institute, Fudan Universitygrid.8547.e, Shanghai, China.

Integrative analysis of high-quality metagenomics and metabolomics data from fecal samples provides novel clues for the mechanism underpinning gut microbe-human interactions. However, data regarding the influence of fecal collection methods on both metagenomics and metabolomics are sparse. Six fecal collection methods (the gold standard [GS] [i.e., immediate freezing at -80°C with no solution], 95% ethanol, RNAlater, OMNIgene Gut, fecal occult blood test [FOBT] cards, and Microlution) were used to collect 88 fecal samples from eight healthy volunteers for whole-genome shotgun sequencing (WGSS) and untargeted metabolomic profiling. Metrics assessed included the abundances of predominant phyla and α- and β-diversity at the species, gene, and pathway levels. Intraclass correlation coefficients (ICCs) were calculated for microbes and metabolites to estimate (i) stability (day 4 versus day 0 within each method), (ii) concordance (day 0 for each method versus the GS), and (iii) reliability (day 4 for each method versus the GS). For the top 4 phyla and microbial diversity metrics at the species, gene, and pathway levels, generally high stability and reliability were observed for most methods except for 95% ethanol; similar concordances were seen for different methods. For metabolomics data, 95% ethanol showed the highest stability, concordance, and reliability (median ICCs = 0.71, 0.71, and 0.65, respectively). Taken together, OMNIgene Gut, FOBT cards, RNAlater, and Microlution, but not 95% ethanol, were reliable collection methods for gut metagenomic studies. However, 95% ethanol was the best for preserving fecal metabolite profiles. We recommend using separate collecting methods for gut metagenomic sequencing and fecal metabolomic profiling in large population studies. The choice of fecal collection method is essential for studying gut microbe-human interactions in large-scale population-based research. In this study, we examined the effects of fecal collection methods and storage time at ambient temperature on variations in the gut microbiome community composition; microbial diversity metrics at the species, gene, and pathway levels; antibiotic resistance genes; and metabolome profiling. Our findings suggest using different fecal sample collection methods for different data generation purposes. OMNIgene Gut, FOBT cards, RNAlater, and Microlution, but not 95% ethanol, were reliable collection methods for gut metagenomic studies. However, 95% ethanol was the best for preserving fecal metabolite profiles.
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http://dx.doi.org/10.1128/mSphere.00636-21DOI Listing
September 2021

A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells.

Mol Med Rep 2021 10 20;24(4). Epub 2021 Aug 20.

Department of Vascular Surgery, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China.

Vascular smooth muscle cells (VSMCs) serve a decisive role in intimal hyperplasia, a common pathophysiological process that leads to numerous vascular disorders. The present study aimed to investigate the unknown mechanisms underlying VSMC phenotypic modulation and identified a novel microRNA (miRNA/miR)‑17‑5p/homeobox B13 (HOXB13) axis involved in the phenotypic switching, proliferation and migration of VSMCs. VSMCs were isolated from the thoracic aorta of Sprague‑Dawley rats, cell proliferation was determined by Cell Counting Kit‑8 (CCK‑8) assay, cell migration was examined by Transwell migration assay and gene expression was detected using reverse transcription‑quantitative PCR and western blot analyses. It was firstly found that incubation with platelet‑derived growth factor‑BB (PDGF‑BB) recombinant protein resulted in a significant increase in HOXB13 expression in VSMCs. Using multiple miRNA prediction tools, miR‑17‑5p was identified as a potential regulator for HOXB13, since it had a 7‑base perfect binding site and a 5‑base imperfect binding site with the 3'‑untranslated region of HOXB13 mRNA, and these sequences were highly conserved across species. The regulatory effect of miR‑17‑5p on HOXB13 was validated using luciferase reporter assays. The expression level of miR‑17‑5p was increased in VSMCs under PDGF‑BB stimulation, and was negatively correlated with HOXB13 mRNA and protein expression. Moreover, the miR‑17‑5p mimics significantly inhibited the proliferation and migration of VSMCs, while antagomiR‑17‑5p showed the opposite effects, which could be abolished by HOXB13 knockdown. The miR‑17‑5p/HOXB13 axis also regulated the expression levels of the markers of differentiated VSMCs (α‑smooth muscle actin, transgelin and smoothelin), proliferating cell nuclear antigen and cell migration proteins, including MMP‑2 and ‑9. In conclusion, the present study demonstrated that miR‑17‑5p inhibited the phenotypic modulation VSMCs stimulated by PDGF‑BB by downregulating HOXB13, indicating that these factors may be potential therapeutic targets for intimal hyperplasia.
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http://dx.doi.org/10.3892/mmr.2021.12370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404093PMC
October 2021

3,5,6-trichloro-2-pyridinol intensifies the effect of chlorpyrifos on the paracrine function of Sertoli cells by preventing binding of testosterone and the androgen receptor.

Toxicology 2021 Aug 3;460:152883. Epub 2021 Aug 3.

Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing, 100083, China.

3,5,6-Trichloro-2-pyridinol (TCP) is an important biomarker and one of the final metabolites of chlorpyrifos (CPF). TCP inhibits secretion of sex hormones. Similar to CPF, TCP can bind to sex steroid hormone receptors and decrease the secretion of sex hormones. However, little attention has been paid to the ability of TCP and CPF to interfere with androgen receptor (AR) in Sertoli cells. This study aimed to explain how TCP promotes the inhibitory effect of CPF on the paracrine function of Sertoli cells. Western blotting indicated that after 20 weeks of exposure, expression of AR in testes was significantly reduced by CPF. An in vitro assay measured the cytotoxicity of CPF, TCP and diethylphosphate (DEP) on viability of Sertoli cells by Cell Counting Kit-8. CPF cytotoxicity was greater than that of TCP, and TCP cytotoxicity was greater than that of DEP at concentrations of 1000 μmol/L. Western blotting indicated that TCP and CPF both decreased expression of AR and cAMP-response element binding protein phosphorylation, while DEP had no effect in Sertoli cells, which are important in regulating paracrine function of Sertoli cells. The fluorescence measurements and docking studies revealed that testosterone, CPF and TCP showed four types of intermolecular interactions with AR, highlighting alkyl bonds with some of the same amino acids. Compared with testosterone, CPF and TCP also showed significant synergistic interaction with AR. CPF interacted with more amino acids and interaction energy than TCP did. This research elucidates TCP in the antiandrogenic effect of CPF on the paracrine function and suggests that TCP or chemicals with a trichloropyridine structure must be considered during reproductive toxicity assessment of potential environmental pollutants.
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http://dx.doi.org/10.1016/j.tox.2021.152883DOI Listing
August 2021

On the origin of SARS-CoV-2-The blind watchmaker argument.

Sci China Life Sci 2021 09 16;64(9):1560-1563. Epub 2021 Jul 16.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

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http://dx.doi.org/10.1007/s11427-021-1972-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284035PMC
September 2021

Soft pneumatic elbow exoskeleton reduces the muscle activity, metabolic cost and fatigue during holding and carrying of loads.

Sci Rep 2021 Jun 15;11(1):12556. Epub 2021 Jun 15.

Institute of Sport Science, Technical University Darmstadt, 64289, Darmstadt, Germany.

To minimize fatigue, sustain workloads, and reduce the risk of injuries, the exoskeleton Carry was developed. Carry combines a soft human-machine interface and soft pneumatic actuation to assist the elbow in load holding and carrying. We hypothesize that the assistance of Carry would decrease, muscle activity, net metabolic rate, and fatigue. With Carry providing 7.2 Nm of assistance, we found reductions of up to 50% for the muscle activity, up to 61% for the net metabolic rate, and up to 99% for fatigue in a group study of 12 individuals. Analyses of operation dynamics and autonomous use demonstrate the applicability of Carry to a variety of use cases, presumably with increased benefits for increased assistance torque. The significant benefits of Carry indicate this device could prevent systemic, aerobic, and/or possibly local muscle fatigue that may increase the risk of joint degeneration and pain due to lifting, holding, or carrying.
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http://dx.doi.org/10.1038/s41598-021-91702-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206112PMC
June 2021

Silver nanoparticles protect against arsenic induced genotoxicity via attenuating arsenic bioaccumulation and elevating antioxidation in mammalian cells.

J Hazard Mater 2021 07 5;413:125287. Epub 2021 Feb 5.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences; Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, PR China. Electronic address:

Arsenic (As) and its compounds have been classified as Group I carcinogenic agents by the International Agency for Research on Cancer (IARC); however, there is few specific and efficient antidotes used for As detoxification. The present study aimed to investigate the protective effects of silver nanoparticles (AgNPs) at non-toxic concentrations on As(Ⅲ) induced genotoxicity and the underlying mechanism. Our data showed that AgNPs pretreatment significantly inhibited the generation of phosphorylated histone H2AX (γ-H2AX, marker of nuclear DNA double strand breaks) and the mutation frequencies induced by As(Ⅲ) exposure. Atomic fluorescence spectrometer (AFS) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis revealed that the intracellular accumulation of As(Ⅲ) in human-hamster hybrid A cells was declined by AgNPs via suppressing the expression of specific As(Ⅲ)-binding protein (Gal-1). Moreover, the activities of antioxidant enzymes were greatly up-regulated by AgNPs, which eventually inhibited the generation of reactive oxygen species (ROS) induced by As(Ⅲ) and the downstream stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathway. These results provided clear evidence that AgNPs dramatically suppressed the genotoxic response of As(Ⅲ) in mammalian cells via decreasing As(Ⅲ) bioaccumulation and elevating intracellular antioxidation, which might provide a new clue for AgNPs applications in As(Ⅲ) detoxification.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125287DOI Listing
July 2021

Engineering the acyltransferase domain of epothilone polyketide synthase to alter the substrate specificity.

Microb Cell Fact 2021 Apr 21;20(1):86. Epub 2021 Apr 21.

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.

Background: Polyketide synthases (PKSs) include ketone synthase (KS), acyltransferase (AT) and acyl carrier protein (ACP) domains to catalyse the elongation of polyketide chains. Some PKSs also contain ketoreductase (KR), dehydratase (DH) and enoylreductase (ER) domains as modification domains. Insertion, deletion or substitution of the catalytic domains may lead to the production of novel polyketide derivatives or to the accumulation of desired products. Epothilones are 16-membered macrolides that have been used as anticancer drugs. The substrate promiscuity of the module 4 AT domain of the epothilone PKS (EPOAT4) results in production of epothilone mixtures; substitution of this domain may change the ratios of epothilones. In addition, there are two dormant domains in module 9 of the epothilone PKS. Removing these redundant domains to generate a simpler and more efficient assembly line is a desirable goal.

Results: The substitution of module 4 drastically diminished the activity of epothilone PKS. However, with careful design of the KS-AT linker and the post-AT linker, replacing EPOAT4 with EPOAT2, EPOAT6, EPOAT7 or EPOAT8 (specifically incorporating methylmalonyl-CoA (MMCoA)) significantly increased the ratio of epothilone D (4) to epothilone C (3) (the highest ratio of 4:3 = 4.6:1), whereas the ratio of 4:3 in the parental strain Schlegelella brevitalea 104-1 was 1.4:1. We also obtained three strains by swapping EPOAT4 with EPOAT3, EPOAT5, or EPOAT9, which specifically incorporate malonyl-CoA (MCoA). These strains produced only epothilone C, and the yield was increased by a factor of 1.8 compared to that of parental strain 104-1. Furthermore, mutations of five residues in the AT domain identified Ser310 as the critical factor for MMCoA recognition in EPOAT4. Then, the mutation of His308 to valine or tyrosine combined with the mutation of Phe310 to serine further altered the product ratios. At the same time, we successfully deleted the inactive module 9 DH and ER domains and fused the ΨKR domain with the KR domain through an ~ 25-residue linker to generate a productive and simplified epothilone PKS.

Conclusions: These results suggested that the substitution and deletion of catalytic domains effectively produces desirable compounds and that selection of the linkers between domains is crucial for maintaining intact PKS catalytic activity.
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http://dx.doi.org/10.1186/s12934-021-01578-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058987PMC
April 2021

Systematic optimization of the yeast cell factory for sustainable and high efficiency production of bioactive ginsenoside compound K.

Synth Syst Biotechnol 2021 Jun 31;6(2):69-76. Epub 2021 Mar 31.

CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, 300 Fenglin Rd, Shanghai, 200032, China.

Ginsenoside Compound K (CK) has been recognized as a major functional component that is absorbed into the systemic circulation after oral administration of ginseng. CK demonstrates diverse bioactivities. A phase I clinical study indicated that CK was a potential candidate for arthritis therapy. However, a phase II clinical study was suspended because of the high cost associated with the present CK manufacturing approach, which is based on the traditional planting-extracting-biotransforming process. We previously elucidated the complete CK biosynthetic pathway and realized for the first time biosynthesis of CK from glucose by engineered yeast. However, CK production was not sufficient for industrial application. Here, we systematically engineered to achieve high titer production of CK from glucose using a previously constructed protopanaxadiol (PPD)-producing chassis, optimizing UGTPg1 expression, improving UDP-glucose biosynthesis, and tuning down UDP-glucose consumption. Our final engineered yeast strain produced CK with a titer of 5.74 g/L in fed-batch fermentation, which represents the highest CK production in microbes reported to date. Once scaled-up, this high titer microbial biosynthesis platform will enable a robust and stable supply of CK, thus facilitating study and medical application of CK.
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http://dx.doi.org/10.1016/j.synbio.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040117PMC
June 2021

Evolutionary analysis and lineage designation of SARS-CoV-2 genomes.

Sci Bull (Beijing) 2021 Feb 6. Epub 2021 Feb 6.

State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing, 100871, China.

The pandemic due to the SARS-CoV-2 virus, the etiological agent of Coronavirus Disease 2019 (COVID-19), has caused immense global disruption. With the rapid accumulation of SARS-CoV-2 genome sequences, however, thousands of genomic variants of SARS-CoV-2 are now publicly available. To improve the tracing of the viral genomes' evolution during the development of the pandemic, we analyzed single nucleotide variants (SNVs) in 121,618 high-quality SARS-CoV-2 genomes. We divided these viral genomes into two major lineages (L and S) based on variants at sites 8782 and 28144, and further divided the L lineage into two major sublineages (L1 and L2) using SNVs at sites 3037, 14408, and 23403. Subsequently, we categorized them into 130 sublineages (37 in S, 35 in L1, and 58 in L2) based on marker SNVs at 201 additional genomic sites. This lineage/sublineage designation system has a hierarchical structure and reflects the relatedness among the subclades of the major lineages. We also provide a companion website (www.covid19evolution.net) that allows users to visualize sublineage information and upload their own SARS-CoV-2 genomes for sublineage classification. Finally, we discussed the possible roles of compensatory mutations and natural selection during SARS-CoV-2's evolution. These efforts will improve our understanding of the temporal and spatial dynamics of SARS-CoV-2's genome evolution.
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http://dx.doi.org/10.1016/j.scib.2021.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864783PMC
February 2021

Intratracheally instillated diesel PM significantly altered the structure and composition of indigenous murine gut microbiota.

Ecotoxicol Environ Saf 2021 Mar 9;210:111903. Epub 2021 Jan 9.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, CAS; Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, High Magnetic Field Laboratory of Hefei Institutes of Physical Science, CAS, Hefei, Anhui 230031, China; Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China. Electronic address:

A diverse and large community of gut microbiota reside in the intestinal tract of various organisms and play important roles in metabolism and immune homeostasis of its host. The disorders of microbiota-host interaction have been closely associated with numerous chronic inflammatory and metabolic diseases, including inflammatory bowel disease and type 2 diabetes. The accumulating evidence has shown that fine particulate matter (PM) exposure contributes to the diabetes, atherosclerosis and inflammatory bowel diseases; however, few studies have explored the impact of inhaled diesel PM on gut microbiota in vivo. In this study, C57BL/6J mice were exposed to diesel PM for 14 days via intratracheal instillation, and colon tissues and feces were harvested for microbiota analysis. Using high-throughput sequencing technology, we observed that intratracheally instillated diesel PM significantly altered the gut microbiota diversity and community. At the phylum and genus levels, principal coordinate analysis (PCoA) and principal component analysis (PCA) indicated pronounced segregation of microbiota compositions, which were further confirmed by β diversity analysis. As the most affected phylum, Bacteroidetes was greatly diminished by diesel PM. On the genus level, Escherichia, Parabacteroides, Akkermansia, and Oscillibacter were significantly elevated by diesel PM exposure. Our findings provided clear evidence that exposure to diesel PM via intratracheal instillation deteriorated the gastrointestinal (GI) tract and significantly altered the structure and composition of gut microbiota, which might subsequently contribute to the developmental abnormalities of inflammation, immunity and metabolism.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111903DOI Listing
March 2021

Identification of Mutated Peptides in Bladder Cancer From Exomic Sequencing Data Reveals Negative Correlation Between Mutation-Specific Immunoreactivity and Inflammation.

Front Immunol 2020 30;11:576603. Epub 2020 Nov 30.

Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Introduction And Objective: Neoantigen-based immunotherapy is one of the breakthroughs in cancer immunotherapy. Benefit from the Cancer Genome Atlas database, we intended to identify mutant peptides with neoantigen property in bladder cancer (BC). Correlations between the immunoreactivity of candidate neoantigens and clinical manifestations were further analyzed.

Methods: HLA-A*02:01 restricted mutant (MT) and wildtype (WT) peptides were predicted by using whole exome sequencing data of 412 BC patients in the TCGA database. Binding affinity to HLA-A2 molecules was determined by using T2 cell-based binding assay. The immunoreactivity to WT and MT peptides in HLA-A2 BC patients was determined by using an ELISPOT assay upon stimulation with MT and WT peptides individually. Clinical relevance to peptide-specific immunoreactivity was analyzed by Pearson correlation analysis. The disease free survival (DFS) curves were plotted using the Kaplan-Meier method in BC patients with or without mutations and compared using the log-rank test online.

Results: Fifty-seven HLA-A*02:01 restricted WT and MT peptides were selected based on predicted high affinity and expression frequency, among which 12 MT peptides from 12 individual genes exhibited strong affinity to HLA-A2 molecules when compared to WT counterparts. MT peptides induced more peptide-specific IFNγ spot forming units (SFUs) than WT counterparts in HLA-A2 BC patients upon stimulation. They were negatively correlated to the counts of peripheral leukocytes and platelets. Patients with higher C-reactive protein level exhibited lower immunoreactivity to MT peptides. Combination of MT peptides from 6 genes, including , , , , and covered 47.5% of the patients under investigation. Patients harboring combinational mutations in these genes were associated with a longer DFS according to the cBioportal online analysis.

Conclusion: Twelve HLA-A*02:01 restricted MT peptides have been identified exhibiting higher binding affinity to HLA-A2 molecules and stronger immunoreactivity than WT counterparts in BC patients. Combination of MT peptides from six genes might be potential as neoantigen candidates in cancer immunotherapy against BC in the future. Inflammatory modulation is inclined to be a strategy to enhance the efficacy of neoantigen-based immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2020.576603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734250PMC
June 2021

A CRISPR-Cas12a-based specific enhancer for more sensitive detection of SARS-CoV-2 infection.

EBioMedicine 2020 Nov 9;61:103036. Epub 2020 Oct 9.

Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.

Background: Real-time reverse transcription-PCR (rRT-PCR) has been the most effective and widely implemented diagnostic technology since the beginning of the COVID-19 pandemic. However, fuzzy rRT-PCR readouts with high Ct values are frequently encountered, resulting in uncertainty in diagnosis.

Methods: A Specific Enhancer for PCR-amplified Nucleic Acid (SENA) was developed based on the Cas12a trans-cleavage activity, which is specifically triggered by the rRT-PCR amplicons of the SARS-CoV-2 Orf1ab (O) and N fragments. SENA was first characterized to determine its sensitivity and specificity, using a systematic titration experiment with pure SARS-CoV-2 RNA standards, and was then verified in several hospitals, employing a couple of commercial rRT-PCR kits and testing various clinical specimens under different scenarios.

Findings: The ratio (10 min/5 min) of fluorescence change (FC) with mixed SENA reaction (mix-FCratio) was defined for quantitative analysis of target O and N genes, and the Limit of Detection (LoD) of mix-FCratio with 95% confidence interval was 1.2≤1.6≤2.1. Totally, 295 clinical specimens were analyzed, among which 21 uncertain rRT-PCR cases as well as 4 false negative and 2 false positive samples were characterized by SENA and further verified by next-generation sequencing (NGS). The cut-off values for mix-FCratio were determined as 1.145 for positive and 1.068 for negative.

Interpretation: SENA increases both the sensitivity and the specificity of rRT-PCR, solving the uncertainty problem in COVID-19 diagnosis and thus providing a simple and low-cost companion diagnosis for combating the pandemic.

Funding: Detailed funding information is available at the end of the manuscript.
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http://dx.doi.org/10.1016/j.ebiom.2020.103036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544594PMC
November 2020

Prediction of Radiosensitivity in Head and Neck Squamous Cell Carcinoma Based on Multiple Omics Data.

Front Genet 2020 18;11:960. Epub 2020 Aug 18.

Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, China.

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor. Radiotherapy (RT) is an important treatment for HNSCC, but not all patients derive survival benefit from RT due to the individual differences on radiosensitivity. A prediction model of radiosensitivity based on multiple omics data might solve this problem. Compared with single omics data, multiple omics data can illuminate more systematical associations between complex molecular characteristics and cancer phenotypes. In this study, we obtained 122 differential expression genes by analyzing the gene expression data of HNSCC patients with RT ( = 287) and without RT ( = 189) downloaded from The Cancer Genome Atlas. Then, HNSCC patients with RT were randomly divided into a training set ( = 149) and a test set ( = 138). Finally, we combined multiple omics data of 122 differential genes with clinical outcomes on the training set to establish a 12-gene signature by two-stage regularization and multivariable Cox regression models. Using the median score of the 12-gene signature on the training set as the cutoff value, the patients were divided into the high- and low-score groups. The analysis revealed that patients in the low-score group had higher radiosensitivity and would benefit from RT. Furthermore, we developed a nomogram to predict the overall survival of HNSCC patients with RT. We compared the prognostic value of 12-gene signature with those of the gene signatures based on single omics data. It suggested that the 12-gene signature based on multiple omics data achieved the best ability for predicting radiosensitivity. In conclusion, the proposed 12-gene signature is a promising biomarker for estimating the RT options in HNSCC patients.
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http://dx.doi.org/10.3389/fgene.2020.00960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461877PMC
August 2020

The unprecedented diversity of UGT94-family UDP-glycosyltransferases in Panax plants and their contribution to ginsenoside biosynthesis.

Sci Rep 2020 09 21;10(1):15394. Epub 2020 Sep 21.

CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences/Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.

More than 150 ginsenosides have been isolated and identified from Panax plants. Ginsenosides with different glycosylation degrees have demonstrated different chemical properties and bioactivity. In this study, we systematically cloned and characterized 46 UGT94 family UDP-glycosyltransferases (UGT94s) from a mixed Panax ginseng/callus cDNA sample with high amino acid identity. These UGT94s were found to catalyze sugar chain elongation at C3-O-Glc and/or C20-O-Glc of protopanaxadiol (PPD)-type, C20-O-Glc or C6-O-Glc of protopanaxatriol (PPT)-type or both C3-O-Glc of PPD-type and C6-O-Glc of PPT-type or C20-O-Glc of PPD-type and PPT-type ginsenosides with different efficiencies. We also cloned 26 and 51 UGT94s from individual P. ginseng and P. notoginseng plants, respectively; our characterization results suggest that there is a group of UGT94s with high amino acid identity but diverse functions or catalyzing activities even within individual plants. These UGT94s were classified into three clades of the phylogenetic tree and consistent with their catalytic function. Based on these UGT94s, we elucidated the biosynthetic pathway of a group of ginsenosides. Our present results reveal a series of UGTs involved in second sugar chain elongation of saponins in Panax plants, and provide a scientific basis for understanding the diverse evolution mechanisms of UGT94s among plants.
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http://dx.doi.org/10.1038/s41598-020-72278-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506552PMC
September 2020

Lower limb joint biomechanics-based identification of gait transitions in between level walking and stair ambulation.

PLoS One 2020 16;15(9):e0239148. Epub 2020 Sep 16.

Technical University of Darmstadt, Darmstadt, Hesse, Germany.

Lower limb exoskeletons and lower limb prostheses have the potential to reduce gait limitations during stair ambulation. To develop robotic assistance devices, the biomechanics of stair ambulation and the required transitions to level walking have to be understood. This study aimed to identify the timing of these transitions, to determine if transition phases exist and how long they last, and to investigate if there exists a joint-related order and timing for the start and end of the transitions. Therefore, this study analyzed the kinematics and kinetics of both transitions between level walking and stair ascent, and between level walking and stair descent (12 subjects, 25.4 yrs, 74.6 kg). We found that transitions primarily start within the stance phase and end within the swing phase. Transition phases exist for each limb, all joints (hip, knee, ankle), and types of transitions. They have a mean duration of half of one stride and they do not last longer than one stride. The duration of the transition phase for all joints of a single limb in aggregate is less than 35% of one stride in all but one case. The distal joints initialize stair ascent, while the proximal joints primarily initialize the stair descent transitions. In general, the distal joints complete the transitions first. We believe that energy- and balance-related processes are responsible for the joint-specific transition timing. Regarding the existence of a transition phase for all joints and transitions, we believe that lower limb exoskeleton or prosthetic control concepts should account for these transitions in order to improve the smoothness of the transition and to thus increase the user comfort, safety, and user experience. Our gait data and the identified transition timings can provide a reference for the design and the performance of stair ambulation- related control concepts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239148PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494088PMC
November 2020

Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea.

Microb Cell Fact 2020 Sep 15;19(1):180. Epub 2020 Sep 15.

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.

Background: Epothilone B is a natural product that stabilizes microtubules, similar to paclitaxel (Taxol); therefore, epothilone B and several derivatives have shown obvious antitumour activities. Some of these products are in clinical trials, and one (ixabepilone, BMS) is already on the market, having been approved by the FDA in 2007. The terminal step in epothilone B biosynthesis is catalysed by the cytochrome P450 enzyme EpoK (CYP167A1), which catalyses the epoxidation of the C12-C13 double bond (in epothilone C and D) to form epothilone A and B, respectively. Although redox partners from different sources support the catalytic activity of EpoK in vitro, the conversion rates are low, and these redox partners are not applied to produce epothilone B in heterologous hosts.

Results: Schlegelella brevitalea DSM 7029 contains electron transport partners that efficiently support the catalytic activity of EpoK. We screened and identified one ferredoxin, Fdx_0135, by overexpressing putative ferredoxin genes in vivo and identified two ferredoxin reductases, FdR_0130 and FdR_7100, by whole-cell biotransformation of epothilone C to effectively support the catalytic activity of EpoK. In addition, we obtained strain H7029-3, with a high epothilone B yield and found that the proportion of epothilone A + B produced by this strain was 90.93%. Moreover, the whole-cell bioconversion strain 7029-10 was obtained; this strain exhibited an epothilone C conversion rate of 100% in 12 h. Further RT-qPCR experiments were performed to analyse the overexpression levels of the target genes. Gene knock-out experiments showed that the selected ferredoxin (Fdx_0135) and its reductases (FdR_0130 and FdR_7100) might participate in critical physiological processes in DSM 7029.

Conclusion: Gene overexpression and whole-cell biotransformation were effective methods for identifying the electron transport partners of the P450 enzyme EpoK. In addition, we obtained an epothilone B high-yield strain and developed a robust whole-cell biotransformation system. This strain and system hold promise for the industrial production of epothilone B and its derivatives.
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http://dx.doi.org/10.1186/s12934-020-01439-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493146PMC
September 2020

Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells.

Int J Mol Sci 2020 Sep 12;21(18). Epub 2020 Sep 12.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences; Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei 230031, China.

Radiotherapy is an important modality for the local control of human cancers, but the radioresistance induced by aberrant apoptotic signaling is a hallmark of cancers. Restoring the aberrant apoptotic pathways is an emerging strategy for cancer radiotherapy. In this study, we determined that targeting cell division cycle 20 (CDC20) radiosensitized colorectal cancer (CRC) cells through mitochondrial-dependent apoptotic signaling. CDC20 was overexpressed in CRC cells and upregulated after radiation. Inhibiting CDC20 activities genetically or pharmacologically suppressed the proliferation and increased radiation-induced DNA damage and intrinsic apoptosis in CRC cells. Mechanistically, knockdown of CDC20 suppressed the expression of antiapoptotic protein Mcl-1 but not other Bcl-2 family proteins. The expressions of CDC20 and Mcl-1 respond to radiation simultaneously through direct interaction, as evidenced by immunoprecipitation and glutathione S-transferase (GST) pull-down assays. Subsequently, decreased Mcl-1 expression inhibited the expression level of phosphorylated checkpoint kinase 1 (p-Chk1), thereby resulting in impaired DNA damage repair through downregulating the homologous recombination repair protein Rad51 and finally causing apoptotic signaling. In addition, both CDC20 and Chk1 inhibitors together, through in vivo studies, confirmed the radiosensitizing effect of CDC20 via inhibiting Mcl-1 and p-Chk1 expression. In summary, our results indicate that targeting CDC20 is a promising strategy to improve cancer radiotherapy.
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http://dx.doi.org/10.3390/ijms21186692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555290PMC
September 2020

Magnetic Skyrmions in a Hall Balance with Interfacial Canted Magnetizations.

Adv Mater 2020 Sep 2;32(38):e1907452. Epub 2020 Aug 2.

School of Materials Science and Engineering, Beijing Advanced Innovation Center for Materials Genome Engineering, University of Science and Technology Beijing, Beijing, 100083, China.

Magnetic skyrmions are attracting interest as efficient information-storage devices with low energy consumption, and have been experimentally and theoretically investigated in multilayers including ferromagnets, ferrimagnets, and antiferromagnets. The 3D spin texture of skyrmions demonstrated in ferromagnetic multilayers provides a powerful pathway for understanding the stabilization of ferromagnetic skyrmions. However, the manipulation mechanism of skyrmions in antiferromagnets is still lacking. A Hall balance with a ferromagnet/insulating spacer/ferromagnet structure is considered to be a promising candidate to study skyrmions in synthetic antiferromagnets. Here, high-density Néel-type skyrmions are experimentally observed at zero field and room temperature by Lorentz transmission electron microscopy in a Hall balance (core structure [Co/Pt] /NiO/[Co/Pt] ) with interfacial canted magnetizations because of interlayer ferromagnetic/antiferromagnetic coupling between top and bottom [Co/Pt] multilayers, where the Co layers in [Co/Pt] are always ferromagnetically coupled. Micromagnetic simulations show that the generation and density of skyrmions are strongly dependent on interlayer exchange coupling (IEC) and easy-axis orientation. Direct experimental evidence of skyrmions in synthetic antiferromagnets is provided, suggesting that the proposed approach offers a promising alternative mechanism for room-temperature spintronics.
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http://dx.doi.org/10.1002/adma.201907452DOI Listing
September 2020

CRISPR-Cas12a-Assisted Genome Editing in .

Front Bioeng Biotechnol 2020 26;8:698. Epub 2020 Jun 26.

College of Life Sciences, Shanghai Normal University, Shanghai, China.

U32 is an industrial producer of rifamycin SV, whose derivatives have long been the first-line antimycobacterial drugs. In order to perform genetic modification in this important industrial strain, a lot of efforts have been made in the past decades and a homologous recombination-based method was successfully developed in our laboratory, which, however, requires the employment of an antibiotic resistance gene for positive selection and did not support convenient markerless gene deletion. Here in this study, the clustered regularly interspaced short palindromic repeat (CRISPR) system was employed to establish a genome editing system in U32. Specifically, the subsp. () gene was first integrated into the U32 genome to generate target-specific double-stranded DNA (dsDNA) breaks (DSBs) under the guidance of CRISPR RNAs (crRNAs). Then, the DSBs could be repaired by either the non-homologous DNA end-joining (NHEJ) system or the homology-directed repair (HDR) pathway, generating inaccurate or accurate mutations in target genes, respectively. Besides of , the present work may also shed light on the development of CRISPR-assisted genome editing systems in other species of the genus.
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http://dx.doi.org/10.3389/fbioe.2020.00698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332547PMC
June 2020

Therapeutic Effect of and Hederagenin on Chronic Neuropathic Pain of Chronic Constriction Injury of Sciatic Nerve Rats Based on KEGG Pathway Prediction and Experimental Verification.

Evid Based Complement Alternat Med 2020 13;2020:2545806. Epub 2020 Jun 13.

College of Traditional Chinese Medicine, Jinan University, Guangzhou 510630, China.

Background: Hederagenin is one of the main components of , and is one of the ingredients of Danggui Sini decoction. To explore whether and hederagenin can alleviate mechanical pain, thermal hyperalgesia, and cold pain at the same time, we comprehensively investigated the effects of two drugs on the levels of p38 MAPK phosphorylation, TRP proteins, and IL1, IL6, and TNF- in serum.

Methods: Firstly, we obtained pain-related targets and performed KEGG pathway enrichment on these targets. Then, 42 SD rats were separated randomly into six groups: sham operation group, CCI group, pregabalin group, mecobalamin group, group, and hederagenin group. All drugs were given orally. Rats in the sham operation group and CCI group were gavaged with saline. Rats in the pregabalin group were given pregabalin, while rats in the mecobalamin group were given mecobalamin. Rats in the group were given , while rats in the hederagenin group were given hederagenin. Besides, we conducted behavioral tests including acetone test, hot plate experiment, and von Frey filaments, and then dorsal root ganglion neurons were taken out on the 21st day after operation. Then, western blot, ELISA, and hematoxylin-eosin staining were conducted.

Results: Rats in the CCI group were more sensitive to hyperalgesia and allodynia to mechanical and thermal stimuli, as well as cold pain. All four drugs could relieve these pains. Pregabalin, mecobalamin, and can reduce the levels of IL1, IL6, and TNF- in serum compared to those of the CCI group. The expression of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in DRG increased evidently on the 21st day after the operation in the CCI group. All four drugs could reduce the expressions of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in dorsal root ganglion compared to those of the CCI group.

Conclusion: and hederagenin relieved sciatica by reducing inflammation levels, inhibiting p38 MAPK phosphorylation, and decreasing the levels of dorsal root ganglion proteins.
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http://dx.doi.org/10.1155/2020/2545806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306840PMC
June 2020

Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1.

Front Cell Dev Biol 2020 12;8:408. Epub 2020 Jun 12.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Radiotherapy is an essential curative treatment modality for colorectal cancer. Apoptosis is the major mechanism of IR-induced cell death and aberrant apoptotic signaling results in radioresistance, which is a hallmark of most, perhaps all, types of human cancers. Potentiating the induction of apoptosis is an emerging strategy for cancer radiotherapy. Here, we determined that targeting CDK8 selectively radiosensitized colorectal cancer through the mitochondria-dependent intrinsic apoptotic signaling, which was mediated through the induction of the transcription of apaf1 that was e2f1- and not p53-dependent. Importantly, the enhanced transcriptional activity of e2f1 was dependent on the kinase activity of CDK8 itself and not on the assembling of the mediator complex. In addition, clinical inhibitor, and studies confirmed the radiosensitizing effect of CDK8. Our results provide a new targeting strategy to improve the radiotherapy of CRC.
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http://dx.doi.org/10.3389/fcell.2020.00408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304162PMC
June 2020

TCP structure intensified the chlorpyrifos-induced decrease in testosterone synthesis via LH-LHR-PKA-CREB-Star pathway.

Sci Total Environ 2020 Jul 8;726:138496. Epub 2020 Apr 8.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

Similar to diethylphosphate (DEP), 3,5,6-trichloro-2-pyridinol (TCP) is also a characteristic chemical substance and ultimate transformation product of chlorpyrifos (CPF) because the structure of TCP is equivalent to the trichloro pyridine structure of CPF. TCP is often used as a biomarker of CPF exposure. TCP and DEP are often detected in human blood and urine due to the widespread use of CPF. No studies have sufficiently clarified which structure contributes to the negative effect of CPF on testosterone synthesis. This study aims to explain which structure promotes the inhibitory effect of CPF on testosterone synthesis and the related influence mechanisms. After 20 weeks of exposure, the testosterone level in testes was significantly reduced by different doses of CPF (0.3 mg/kg body weight CPF and 3.0 mg/kg body weight CPF). Meanwhile, the level of testosterone synthesized by isolated primary Leydig cells was also reduced by CPF. In addition, TCP but not DEP aggravated the decrease in testosterone synthesis in isolated primary Leydig cells. On the other hand, CPF and TCP significantly decreased the levels of the Star protein, CREB phosphorylation and PKA phosphorylation, which are important in regulating testosterone synthesis. Based on these results, TCP is a key structure that mediates the CPF-induced decrease in testosterone synthesis by terminating the signal transmission of the LH-LHR-PKA-CREB-Star pathway. Thus, chemicals with the TCP structure may be potential endocrine disruptors that decrease fertility. Chemicals that can be converted to TCP or achieve a trichloro pyridine structure must be considered during reproductive toxicity risk assessment.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138496DOI Listing
July 2020

Prevalence of / pathogenic variation in Chinese Han population.

J Med Genet 2021 Aug 28;58(8):565-569. Epub 2020 May 28.

Faculty of Health Sciences, University of Macau, Macau, China

Background: Pathogenic variation in and () is one of the most frequent genetic predispositions for hereditary breast cancer. The identification of the variant carriers plays an important role in prevention and treatment of cancer. Despite a population size of 1.4 billion and a quarter million annual new breast cancer cases, knowledge regarding the prevalence of variation in the Chinese population remains elusive.

Methods: In this study, we used -targeted sequencing and bioinformatics approaches to screen for variants in 11 386 Chinese Han individuals, including 9331 females and 2055 males.

Results: We identified 1209 variants, 34 of which were pathogenic, including 11 in and 23 in . These variants were distributed among 43 individuals (37 females and 6 males), with 13 carrying and 30 carrying variants. Based on these data, we determined a prevalence of 0.38%, or 1 carrier of a pathogenic variant out of every 265 Chinese Han individuals, and 5.1 million carriers among the Chinese Han population of 1.3 billion.

Conclusion: Our study provides basic knowledge about the prevalence of pathogenic variation in the Chinese Han population. This information should be valuable for -related cancer prevention and treatment in the population.
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http://dx.doi.org/10.1136/jmedgenet-2020-106970DOI Listing
August 2021

Viral and host factors related to the clinical outcome of COVID-19.

Nature 2020 07 20;583(7816):437-440. Epub 2020 May 20.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China); it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of the epidemiology, transmissibility and pathogenesis of COVID-19. Here we analysed clinical, molecular and immunological data from 326 patients with confirmed SARS-CoV-2 infection in Shanghai. The genomic sequences of SARS-CoV-2, assembled from 112 high-quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) dataset, showed a stable evolution and suggested that there were two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially reduced CD4 and CD8 T cell counts upon hospital admission, was predictive of disease progression. High levels of interleukin (IL)-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age and lymphocytopenia (and its associated cytokine storm), whereas viral genetic variation did not significantly affect outcomes.
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http://dx.doi.org/10.1038/s41586-020-2355-0DOI Listing
July 2020

Epidemiology of Coronavirus Disease 2019 (COVID-19) Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Disaster Med Public Health Prep 2020 12 18;14(6):796-804. Epub 2020 May 18.

TEDA International Cardiovascular Hospital, TianJin, China.

In December, 2019, an infectious outbreak of unknown cause occurred in Wuhan, which attracted intense attention. Shortly after the virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the epidemic of coronavirus disease 2019 (COVID-19) broke out, and an information storm occurred. At that time, 2 important aspects, that is, the stages of spread and the components of the epidemic, were unclear. Answers to the questions (1) what are the sources, (2) how do infections occur, and (3) who will be affected should be clarified as the outbreak continues to evolve. Furthermore, components of the epidemic and the stages of spread should be explored and discussed. Based on information of SARS, Middle East respiratory syndrome (MERS), and COVID-19, the components of the epidemic (the sources, the routes of infection, and the susceptible population) will be discussed, as well as the role of natural and social factors involved. Epidemiologic characteristics of patients will be traced based on current information.
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http://dx.doi.org/10.1017/dmp.2020.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399147PMC
December 2020

Cold atmospheric plasma‑activated Ringer's solution inhibits the proliferation of osteosarcoma cells through the mitochondrial apoptosis pathway.

Oncol Rep 2020 May 25;43(5):1683-1691. Epub 2020 Feb 25.

Department of Orthopedics, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230000, P.R. China.

The present study aimed to investigate the effects of cold atmospheric plasma (CAP)‑activated Ringer's solution on osteosarcoma cell lines MG63 and U2OS, and to identify the molecular mechanism underlying these effects. CAP‑activated Ringer's solution was used to treat osteosarcoma cell lines MG63 and U2OS for 30 min. Cell viability was measured using the MTT method. The apoptosis rate was detected using Annexin‑V and propidium iodide. The expression levels of cytochrome c, caspase‑3 and polyADP ribose polymerase (PARP) in MG63 cells were analyzed via western blotting. The change in mitochondrial membrane potential was detected via the JC‑1 dye method and verified by the level of reactive oxygen species (ROS). CAP‑activated Ringer's solution inhibited the proliferation of MG63 and U2OS cells in a dose‑ and time‑dependent manner. Furthermore, CAP‑activated Ringer's solution induced the apoptosis of MG63 cells, increased the intracellular ROS level, decreased the mitochondrial membrane potential level, and induced the release of cytochrome c. CAP‑activated Ringer's solution inhibits osteosarcoma cell proliferation through intracellular ROS‑mediated mitochondrial apoptosis.
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http://dx.doi.org/10.3892/or.2020.7518DOI Listing
May 2020

Inhibition of basal cell carcinoma cells by cold atmospheric plasma‑activated solution and differential gene expression analysis.

Int J Oncol 2020 05 6;56(5):1262-1273. Epub 2020 Mar 6.

Teaching and Research Section of Nuclear Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Basal cell carcinoma is a common skin tumor. Cold atmospheric plasma (CAP) has attracted increasing attention for its antitumor effects. The aim of the present study was to investigate the effects and related mechanisms of two CAP‑activated solutions on the TE354T basal cell carcinoma and HaCat keratinocyte cell lines. Plasma‑activated solution (PAS) was prepared by CAP irradiation of DMEM and PBS. TE354T cells were treated with PAS in vitro and the effect on cell viability was evaluated by an MTT assay. The apoptosis rate was detected by Annexin V/propidium iodide staining. Furthermore, western blotting and RNA‑sequencing were performed. The present results demonstrated that PAS induced apoptotic signaling in basal cell carcinoma cells, and that this effect was associated with the activation of the MAPK signaling pathway. Therefore, the present study demonstrated that PAS may serve as a novel treatment for basal cell carcinoma.
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http://dx.doi.org/10.3892/ijo.2020.5009DOI Listing
May 2020

A ferromagnetic skyrmion-based diode with a voltage-controlled potential barrier.

Nanoscale 2020 May 21;12(17):9507-9516. Epub 2020 Apr 21.

College of Physics and Electronic Engineering, Sichuan Normal University, Chengdu 610068, China.

Traditional electronic technologies face many challenges, such as the scalability of equipment and improvement of performance. Some novel spintronic objects are expected to improve electronic applications for the more-than-Moore era. For example, a magnetic skyrmion is a potential building block for the next generation of electronic devices due to its small size, good stability and low driving current threshold. However, the Magnus force acting on a ferromagnetic skyrmion can induce a transverse motion perpendicular to the driving force, which may lead to the destruction of skyrmions at sample edges. Here, we computationally demonstrate that the nanotrack edge with high magnetic perpendicular anisotropy (PMA), which is controlled by the voltage-controlled magnetic anisotropy (VCMA) effect, not only enables the reliable motion of skyrmions along the nanotrack, but also increases the skyrmion velocity. The one-way motion of skyrmions can be realized by applying voltage to create high PMA at a local area near the nanotrack edge. In addition, we show a feasible design of a skyrmion diode similar to the P-N junction. Our results may provide guidelines for designing skyrmion-based diodes.
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http://dx.doi.org/10.1039/c9nr10528jDOI Listing
May 2020

Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers.

Cancers (Basel) 2020 Apr 13;12(4). Epub 2020 Apr 13.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences; Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei 230031, China.

Response to radiotherapy (RT) in cancers varies widely among patients. Therefore, it is very important to predict who will benefit from RT before clinical treatment. Consideration of the immune tumor microenvironment (TME) could provide novel insight into tumor treatment options. In this study, we investigated the link between immune infiltration status and clinical RT outcome in order to identify certain leukocyte subsets that could potentially influence the clinical RT benefit across cancers. By integrally analyzing the TCGA data across seven cancers, we identified complex associations between immune infiltration and patients RT outcomes. Besides, immune cells showed large differences in their populations in various cancers, and the most abundant cells were resting memory CD4 T cells. Additionally, the proportion of activated CD4 memory T cells and activated mast cells, albeit at low number, were closely related to RT overall survival in multiple cancers. Furthermore, a prognostic model for RT outcomes was established with good performance based on the immune infiltration status. Summarized, immune infiltration was found to be of significant clinical relevance to RT outcomes. These findings may help to shed light on the impact of tumor-associated immune cell infiltration on cancer RT outcomes, and identify biomarkers and therapeutic targets.
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http://dx.doi.org/10.3390/cancers12040957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226004PMC
April 2020
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