Publications by authors named "Yuchuan Li"

29 Publications

  • Page 1 of 1

Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats.

Front Neurosci 2021 27;15:645849. Epub 2021 Apr 27.

Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, China.

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson's disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12-35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD.
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http://dx.doi.org/10.3389/fnins.2021.645849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111217PMC
April 2021

Effects of intrastriatal injection of the dopamine receptor agonist SKF38393 and quinpirole on locomotor behavior in hemiparkinsonism rats.

Behav Brain Res 2021 May 1;411:113339. Epub 2021 May 1.

Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, People's Republic of China. Electronic address:

Dopamine (DA) in the striatum is essential to influence motor behavior and may lead to movement impairment in Parkinson's disease (PD). The present study examined the different functions of the DA D1 receptor (D1R) and DA D2 receptor (D2R) by intrastriatal injection of the D1R agonist SKF38393 and the D2R agonist quinpirole in 6-hydroxydopamine (6-OHDA)-lesioned and control rats. All rats separately underwent dose-response behavior testing for SKF38393 (0, 0.5, 1.0, and 1.5 μg/site) or quinpirole (0, 1.0, 2.0, and 3.0 μg/site) to determine the effects of the optimal modulating threshold dose. Two behavior assessment indices, the time of latency to fall and the number of steps on a rotating treadmill, were used as reliable readouts of motor stimulation variables for quantifying the motor effects of the drugs. The findings indicate that at threshold doses, SKF38393 (1.0 μg/site) and quinpirole (1.0 μg/site) produce a dose-dependent increase in locomotor activity compared to vehicle injection. The ameliorated behavioral responses to either SKF38393 or quinpirole in lesioned rats were greater than those in unlesioned control rats. Moreover, the dose-dependent increase in locomotor capacity for quinpirole was greater than that for SKF38393 in lesioned rats. These results can clarify several key issues related to DA receptors directly and may provide a basis for exploring the potential of future selective dopamine therapies for PD in humans.
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http://dx.doi.org/10.1016/j.bbr.2021.113339DOI Listing
May 2021

Plin2 deletion increases cholesteryl ester lipid droplet content and disturbs cholesterol balance in adrenal cortex.

J Lipid Res 2021 Feb 11;62:100048. Epub 2021 Feb 11.

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; The Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address:

Cholesteryl esters (CEs) are the water-insoluble transport and storage form of cholesterol. Steroidogenic cells primarily store CEs in cytoplasmic lipid droplet (LD) organelles, as contrasted to the majority of mammalian cell types that predominantly store triacylglycerol (TAG) in LDs. The LD-binding Plin2 binds to both CE- and TAG-rich LDs, and although Plin2 is known to regulate degradation of TAG-rich LDs, its role for regulation of CE-rich LDs is unclear. To investigate the role of Plin2 in the regulation of CE-rich LDs, we performed histological and molecular characterization of adrenal glands from Plin2 and Plin2 mice. Adrenal glands of Plin2 mice had significantly enlarged organ size, increased size and numbers of CE-rich LDs in cortical cells, elevated cellular unesterified cholesterol levels, and increased expression of macrophage markers and genes facilitating reverse cholesterol transport. Despite altered LD storage, mobilization of adrenal LDs and secretion of corticosterone induced by adrenocorticotropic hormone stimulation or starvation were similar in Plin2 and Plin2 mice. Plin2 adrenals accumulated ceroid-like structures rich in multilamellar bodies in the adrenal cortex-medulla boundary, which increased with age, particularly in females. Finally, Plin2 mice displayed unexpectedly high levels of phosphatidylglycerols, which directly paralleled the accumulation of these ceroid-like structures. Our findings demonstrate an important role of Plin2 for regulation of CE-rich LDs and cellular cholesterol balance in the adrenal cortex.
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http://dx.doi.org/10.1016/j.jlr.2021.100048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044703PMC
February 2021

NFAT5 Regulated by STUB1, Facilitates Malignant Cell Survival and p38 MAPK Activation by Upregulating AQP5 in Chronic Lymphocytic Leukemia.

Biochem Genet 2021 Feb 5. Epub 2021 Feb 5.

Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, Guangdong, China.

Chronic lymphocytic leukemia (CLL) is a clonal proliferative disease of mature B lymphocytes. To further improve the prognosis of patients, it is necessary to further elucidate the pathogenesis of CLL and find more effective therapeutic targets. Nuclear Factor of Activated T cells 5 (NFAT5) is the major activated transcription factor (TF) upon osmotic pressure increase in mammalian cells, and it also regulates many target genes to affect various cellular functions. The effects of NFAT5 on tumor growth and metastasis have also been widely revealed. However, the effects of NFAT5 on the progression of CLL are still unclear. In this study, we found abnormally high expression of NFAT5 in human CLL patients. Additionally, NFAT5 depletion suppressed proliferation and stimulated apoptosis of CLL cells. Our data further confirmed NFAT5 regulated AQP5 expression and the phosphorylation of p38 MAPK. We also found that AQP5 overexpression reversed the inhibitory effect of NFAT5 depletion on cell proliferation in CLL cells. Furthermore, we revealed STUB1 directly bound to NFAT5 and promoted its degradation. Taken together, our results indicate the involvement of NFAT5 in CLL progression and suggest that NFAT5 could serve as a promising therapeutic target for CLL treatment.
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http://dx.doi.org/10.1007/s10528-021-10040-3DOI Listing
February 2021

Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Apr 26;1866(4):158873. Epub 2020 Dec 26.

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway; The Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Norway. Electronic address:

Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adult Plin5 and Plin5 mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated from Plin5 mice cultured with oleic acid stored less LDs than Plin5, but comparable levels to Plin5 cardiomyocytes when adipose triglyceride lipase activity was inhibited. The ability to oxidize fatty acids into CO was similar between Plin5 and Plin5 cardiomyocytes, but Plin5 cardiomyocytes had a transient increase in intracellular fatty acid oxidation intermediates. After pre-incubation with oleic acids, Plin5 cardiomyocytes retained a higher content of glycogen and showed improved tolerance to hypoxia compared to Plin5. In isolated, perfused hearts, deletion of Plin5 had no important effect on ventricular pressures or infarct size after ischemia. Old Plin5 mice had reduced levels of cardiac triacylglycerides, increased heart weight, and apart from modest elevated expression of mRNAs for beta myosin heavy chain Myh7 and the fatty acid transporter Cd36, other genes involved in fatty acid oxidation, glycogen metabolism and glucose utilization were essentially unchanged by removal of Plin5. Plin5 seems to facilitate cardiac LD storage primarily by repressing adipose triglyceride lipase activity without altering cardiac fatty acid oxidation capacity. Expression of Plin5 and cardiac LD content of isolated cardiomyocytes has little importance for tolerance to acute hypoxia and ischemia, which contrasts the protective role for Plin5 in mouse models during myocardial ischemia.
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http://dx.doi.org/10.1016/j.bbalip.2020.158873DOI Listing
April 2021

The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy.

BMC Med Genomics 2020 12 4;13(1):181. Epub 2020 Dec 4.

Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530023, Guangxi, China.

Background: Wolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene located within the 165 kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight NSD2 loss of function variants have been reported in patients from different parts of the world, all were de novo variants.

Methods: In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature.

Results: A novel loss of function NSD2 variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more NSD2 mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5 years.

Conclusions: Here we reported the first familial NSD2 variant and the long-term effect of growth hormone therapy for patients. Our results suggested NSD2 mutation might cause a distinct intellectual disability and short stature syndrome.
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http://dx.doi.org/10.1186/s12920-020-00831-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716467PMC
December 2020

Clinical features and predictors of remission in children under the age of 7 years with Graves' disease.

Pediatr Investig 2020 Sep 27;4(3):198-203. Epub 2020 Sep 27.

Department of Endocrinology, Genetics and Metabolism Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: Graves' disease (GD) is rare in children under the age of 7 years. Children with this disease exhibit greater thyrotoxicity at diagnosis and require a longer course of medical therapy, compared with pubertal and postpubertal children and adults.

Objective: To investigate the clinical features and identify predictors of remission in children under the age of 7 years with GD.

Methods: This retrospective study included 77 children who were diagnosed with GD under the age of 7 years and were treated in the Department of Endocrinology, Beijing Children's Hospital from 2010 to 2018. Clinical manifestations, laboratory data, and follow-up records were collected for all patients. Children who achieved remission of treatment with methimazole were compared with those who had persistent disease to identify which variables were associated with remission; multiple logistic regression and Cox regression analyses were used to evaluate interactions among predictive variables.

Results: Sixty-three boys and 14 girls were included; the median age at diagnosis was 4.2 years (interquartile range: 3.2-5.3 years). Forty-six (56.7%) patients had no family history of thyroid disease, 17 patients had family history of thyroid disease and 14 patients with unknown family history. Of the 77 patients, 18 (23.4%) patients achieved remission of treatment with methimazole and 59 patients did not; moreover, 51 (66.2%) had Graves' ophthalmopathy. Univariate analyses revealed no significant differences between the remission group and non-remission group in terms of age at diagnosis, sex, initial goiter size, or initial thyroid hormone concentration. However, there were a trend of correlation between the initial level of thyroid peroxidase antibody (TPOAb) and remission status (univariate analysis 1.002, 0.038; multivariate analysis 1.004, 0.019). Similar results were observed in univariate analysis of the initial thyrotropin receptor antibody (TRAb) level, but this association was not significant in multivariate analysis. Cox regression analyses revealed that children with high TRAb level required longer duration of remission, compared with low TRAb level ( 0.950, 95% 0.904-0.997, 0.037).

Interpretation: Initial TRAb level was an independent predictor of remission outcome in young children under the age of 7 years with GD. Initial TRAb level may predict the likelihood of remission in patients with young-age-of-onset GD.
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http://dx.doi.org/10.1002/ped4.12219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520111PMC
September 2020

Both Gut Microbiota and Differentially Expressed Proteins Are Relevant to the Development of Obesity.

Biomed Res Int 2020 24;2020:5376108. Epub 2020 Sep 24.

The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating the profiles of bacterial communities in fecal samples and differentially expressed proteins (DEPs) in the peripheral blood in mice fed a high-fat diet (HFD) and standard diet (SD) and at providing new insights into the pathogenesis of obesity. The profiles of bacterial communities in fecal samples and DEPs in the peripheral blood were characterized in mice fed HFD and SD, respectively. The levels of 3 DEPs increased in HFD mice. The alpha diversity was significantly lower after 4 and 12 weeks in HFD mice. The beta diversity was higher after 4, 8, and 12 weeks in HFD mice. A total of 16 gut bacterial clades were significantly different with the linear discriminant analysis (LDA) score higher than 4 over time. The relative abundance levels of Proteobacteria and Deferribacteres were higher, while those of Bacteroidetes and Firmicutes were lower in HFD mice at the phylum level. The relative abundance of Desulfovibrionaceae and Rikenellaceae increased in HFD mice at the family level. The relative abundance of the Bacteroidetes_S24-7_group and Lachnospiraceae was lower in HFD mice. The gut microbiota had a significant correlation with serum lipid indexes and expression of DEPs at the phylum and family levels. The changes in the gut microbiota of HFD mice and their associations with the levels of inflammatory proteins could be one of the major etiological mechanisms underlying obesity.
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http://dx.doi.org/10.1155/2020/5376108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533028PMC
April 2021

A Novel, Recurrent, 3.6-kb Deletion in the PYGL Gene Contributes to Glycogen Storage Disease Type VI.

J Mol Diagn 2020 12 19;22(12):1373-1382. Epub 2020 Sep 19.

Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address:

The PYGL gene is the only established gene known to cause glycogen storage disease type VI (GSD6), which is a rare autosomal recessive disorder associated with hepatomegaly, elevated levels of hepatic transaminases, and hypoglycemia. Extended bioinformatics analysis was performed on the exome sequencing data of 5 patients who were clinically diagnosed as having or highly suspected of having GSD, and a single heterozygous pathogenic or likely pathogenic or rare variant of uncertain significance single-nucleotide variant was identified on the PYGL gene. A recurrent, novel, 3.6-kb deletion involving exons 14 to 17 of PYGL was identified in three of the five patients. Together with the two novel and one established stop-gain SNVs, they were diagnosed as compounds heterozygous of PYGL variants and confirmed as GSD6. The detected 3.6-kb deletion was further screened in a Chinese cohort of 31,317 individuals without hepatic abnormalities, and 10 carriers were identified, showing an allele frequency of 0.016%. Compared with the previously established 47 PYGL pathogenic or likely pathogenic SNVs, the novel pathogenic deletion had the second highest allele frequency among the population. This recurrent, novel, 3.6-kb deletion improved the molecular diagnostic rate of the GSD6. The relatively high frequency of the variant suggests that it is a potential mutation hotspot in patients with GSD6.
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http://dx.doi.org/10.1016/j.jmoldx.2020.08.006DOI Listing
December 2020

Long non-coding RNA LINC01268 promotes cell growth and inhibits cell apoptosis by modulating miR-217/SOS1 axis in acute myeloid leukemia.

Braz J Med Biol Res 2020 26;53(8):e9299. Epub 2020 Jun 26.

Department of Hematology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.

The aim of this study was to evaluate the pathogenic role of newly identified long non-coding (lnc)-RNA LINCO1268 in acute myeloid leukemia (AML), and investigate its therapeutic potential. The expression level of LINC01268 in AML was measured by quantitative PCR (qPCR). The viability, cell cycle progression, and apoptosis of AML cells were measured by CCK-8 assay and flow cytometry, respectively. The interaction between LINC01268 and miR-217 were predicted by the miRDB website, and then verified by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The relationship between miR-217 and SOS1 was predicted by TargetScan website, and verified by luciferase reporter assay. LINC01268 was significantly upregulated by 1.6 fold in bone marrow samples of AML patients, which was associated with poor prognosis. LINC01268 was also significantly upregulated in AML cells. LINC01268 knockdown inhibited viability and cell cycle progression but promoted apoptosis of AML cells. Furthermore, LINC01268 functioned as a ceRNA via competitively binding to miR-217, and SOS1 was identified as a target of miR-217. Moreover, LINC01268 positively regulated SOS1 expression to promote AML cell viability and cell cycle progression but inhibited apoptosis via sponging miR-217. LINC01268 promoted cell growth and inhibited cell apoptosis through modulating miR-217/SOS1 axis in AML. This study offers a novel molecular mechanism for a better understanding of the pathology of AML. LINC01268 could be considered as a potential biomarker for the therapy and diagnosis of AML.
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http://dx.doi.org/10.1590/1414-431X20209299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326380PMC
August 2020

Nonvolatile metabolism in postharvest tea (Camellia sinensis L.) leaves: Effects of different withering treatments on nonvolatile metabolites, gene expression levels, and enzyme activity.

Food Chem 2020 Oct 6;327:126992. Epub 2020 May 6.

Key Laboratory of Horticulture Plant Biology, Ministry of Education, College of Horticulture & Forestry Sciences, Huazhong Agricultural University, Wuhan, Hubei 430070, People's Republic of China; Key Laboratory of Urban Agriculture in Central China, Ministry of Agriculture, Wuhan, Hubei 430070, People's Republic of China. Electronic address:

The influence mechanism of different withering methods (CK, indoor natural spreading; LTD, low-temperature plus dark; LTY, low-temperature plus yellow-light; LTCD, low-temperature plus CO) on non-volatile compounds in postharvest tea leaves was investigated by UHPLC-Q-TOF/MS-based non-targeted metabolomic and transcriptomic analyses. Compared with CK, low-temperature withering could slow down polyphenol oxidation by inhibiting polyphenol oxidase activity and keeping the expression of genes for flavanol synthesis. After withering, the proteinaceous amino acid content increased significantly, especially for LTCD and LTY, mainly due to increased peptidase activity and up-regulation of genes involved in the biosynthesis of valine, leucine, aspartic acid, glutamic acid, phenylalanine, and proline. Moreover, LTCD and LTY enhanced the synthesis of γ-aminobutyric acid and metabolism of phenylalanine-methyl salicylate and tryptophan-indole, respectively. Meanwhile, the transformation of theobromine to caffeine was accelerated under low-temperature withering. This research provides ageneticmetabolicbasis for the application of low-temperature withering to actual green tea processing.
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http://dx.doi.org/10.1016/j.foodchem.2020.126992DOI Listing
October 2020

Both gut microbiota and cytokines act to atherosclerosis in ApoE-/- mice.

Microb Pathog 2020 Jan 1;138:103827. Epub 2019 Nov 1.

The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously.

Methods: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis.

Results: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified.

Conclusions: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.
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http://dx.doi.org/10.1016/j.micpath.2019.103827DOI Listing
January 2020

Inhibiting nucleolin reduces inflammation induced by mitochondrial DNA in cardiomyocytes exposed to hypoxia and reoxygenation.

Br J Pharmacol 2019 11 27;176(22):4360-4372. Epub 2019 Oct 27.

Department of Molecular Medicine, Division of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background And Purpose: Cellular debris causes sterile inflammation after myocardial infarction. Mitochondria constitute about 30 percent of the human heart. Mitochondrial DNA (mtDNA) is a damage-associated-molecular-pattern that induce injurious sterile inflammation. Little is known about mtDNA's inflammatory signalling pathways in cardiomyocytes and how mtDNA is internalized to associate with its putative receptor, toll-like receptor 9 (TLR9).

Experimental Approach: We hypothesized that mtDNA can be internalized in cardiomyocytes and induce an inflammatory response. Adult mouse cardiomyocytes were exposed to hypoxia-reoxygenation and extracellular DNA. Microscale thermophoresis was used to demonstrate binding between nucleolin and DNA.

Key Results: Expression of the pro-inflammatory cytokines IL-1β and TNFα were upregulated by mtDNA, but not by nuclear DNA (nDNA), in cardiomyocytes exposed to hypoxia-reoxygenation. Blocking the RNA/DNA binding protein nucleolin with midkine reduced expression of IL-1β/TNFα and the nucleolin inhibitor AS1411 reduced interleukin-6 release in adult mouse cardiomyocytes. mtDNA bound 10-fold stronger than nDNA to nucleolin. In HEK293-NF-κB reporter cells, mtDNA induced NF-κB activity in normoxia, while CpG-DNA and hypoxia-reoxygenation, synergistically induced TLR9-dependent NF-κB activity. Protein expression of nucleolin was found in the plasma membrane of cardiomyocytes and inhibition of nucleolin with midkine inhibited cellular uptake of CpG-DNA. Inhibition of endocytosis did not reduce CpG-DNA uptake in cardiomyocytes.

Conclusion And Implications: mtDNA, but not nDNA, induce an inflammatory response in mouse cardiomyocytes during hypoxia-reoxygenation. In cardiomyocytes, nucleolin is expressed on the membrane and blocking nucleolin reduce inflammation. Nucleolin might be a therapeutic target to prevent uptake of immunogenic DNA and reduce inflammation.

Linked Articles: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc.
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http://dx.doi.org/10.1111/bph.14830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887679PMC
November 2019

A system dynamics modelling simulation based on a cohort of hepatitis B epidemic research in east China community.

Epidemiol Infect 2019 02 28;147:e86. Epub 2019 Feb 28.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Hepatitis B constitutes a severe public health challenge in China. The Community-based Collaborative Innovation hepatitis B (CCI-HBV) project is a national epidemiological study of hepatitis B and has been conducting a comprehensive intervention in southern Zhejiang since 2009.The comprehensive intervention in CCI-HBV areas includes the dynamic hepatitis B screening in local residents, the normalised treatment for hepatitis B infections and the upcoming full-aged hepatitis B vaccination. After two rounds of screening (each round taking for 4 years), the initial epidemiological baseline of hepatitis B in Qinggang was obtained, a coastal community in east China. By combining key data and system dynamics modelling, the regional hepatitis B epidemic in 20 years was predicted.There were 1041 HBsAg positive cases out of 12 228 people in Round 1 indicating HBV prevalence of 8.5%. Of the 13 146 people tested in Round 2, 1171 people were HBsAg positive, with a prevalence of 8.9%. By comparing the two rounds of screening, the HBV incidence rate of 0.192 per 100 person-years was observed. By consulting electronic medical records, the HBV onset rate of 0.533 per 100 person-years was obtained. We generated a simulated model to replicate the real-world situation for the next two decades. To evaluate the effect of interventions on regional HBV prevalence, three comparative experiments were conducted.In this study, the regional hepatitis B epidemic in 20 years was predicted and compared with HBV prevalence under different interventions. Owing to the existing challenges in research methodology, this study combined HBV field research and simulation to provide a system dynamics model with close-to-real key data to improve prediction accuracy. The simulation also provided a prompt guidance for the field implementation.
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http://dx.doi.org/10.1017/S0950268819000220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518579PMC
February 2019

An fluorescent aptasensor for sensitive detection of tumor marker based on the FRET of a sandwich structured QDs-AFP-AuNPs.

Talanta 2019 May 3;197:444-450. Epub 2019 Jan 3.

State Key Laboratory for Diagnosis and Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China. Electronic address:

The detection of alpha-fetoprotein (AFP) is of great importance for hepatocellular carcinoma (HCC) diagnosis, but it needs to be further improved because of poor sensitivity and complicated operating steps. In this paper, a simple and sensitive homogeneous apatasensor for AFP has been developed based on Förster resonance energy transfer (FRET) where the AFP aptamer labeled luminescent CdTe quantum dots (QDs) as a donor and anti-AFP antibody functional gold nanoparticles (AuNPs) as an acceptor. In the presence of AFP, the bio-affinity between aptamer, target, and antibody made the QDs and AuNPs close enough, thus the fluorescence of CdTe QDs quenched though the FRET between QD and AuNP. The fluorescent aptasensor for AFP showed a concentration-dependent decrease of fluorescence intensity in the low nanomolar range and a detecting linear range of 0.5-45 ng mL, with a detection limit of 400 pg mL. Moreover, this homogeneous aptasensor is simple and reliable, and obtained satisfying results for the detection of AFP in human serum samples. With more and more aptamers for biomarkers have been selected gradually, this approach could be easily extended to detection of a wide range of biomarkers. The proposed aptasensor has great potential for carcinoma screening in point-of-care testing and even in field use.
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http://dx.doi.org/10.1016/j.talanta.2019.01.012DOI Listing
May 2019

Higher lipid turnover and oxidation in cultured human myotubes from athletic versus sedentary young male subjects.

Sci Rep 2018 12 3;8(1):17549. Epub 2018 Dec 3.

Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.

In this study we compared fatty acid (FA) metabolism in myotubes established from athletic and sedentary young subjects. Six healthy sedentary (maximal oxygen uptake (VO) ≤ 46 ml/kg/min) and six healthy athletic (VO > 60 ml/kg/min) young men were included. Myoblasts were cultured and differentiated to myotubes from satellite cells isolated from biopsy of musculus vastus lateralis. FA metabolism was studied in myotubes using [C]oleic acid. Lipid distribution was assessed by thin layer chromatography, and FA accumulation, lipolysis and re-esterification were measured by scintillation proximity assay. Gene and protein expressions were studied. Myotubes from athletic subjects showed lower FA accumulation, lower incorporation of FA into total lipids, triacylglycerol (TAG), diacylglycerol and cholesteryl ester, higher TAG-related lipolysis and re-esterification, and higher complete oxidation and incomplete β-oxidation of FA compared to myotubes from sedentary subjects. mRNA expression of the mitochondrial electron transport chain complex III gene UQCRB was higher in cells from athletic compared to sedentary. Myotubes established from athletic subjects have higher lipid turnover and oxidation compared to myotubes from sedentary subjects. Our findings suggest that cultured myotubes retain some of the phenotypic traits of their donors.
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http://dx.doi.org/10.1038/s41598-018-35715-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277406PMC
December 2018

Validity of web-based self-assessment of pubertal development against pediatrician assessments.

Pediatr Investig 2018 Sep 17;2(3):141-148. Epub 2018 Oct 17.

Center for Clinical Epidemiology and Evidence-based Medicine Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Importance: A web-based instrument for self-assessment of puberty could be convenient and feasible for large-scale multicenter population-based epidemiological studies for Tanner stages evaluation.

Objective: To validate web-based self-assessment of pubertal development against assessment by a pediatrician.

Methods: Outpatients aged 8-18 years were consecutively recruited in the endocrinology department of Beijing Children's Hospital from October 2016 to August 2017. A web-based self-assessment instrument for pubertal development was introduced to participants by an appointed pediatrician. Tanner stage of puberty was self-assessed by participants in a private environment. Participants were then examined by a senior pediatrician underwent blinded assessment. Weighted kappa and Spearman correlation analyses were conducted to evaluate agreement. The accuracy of the web-based instrument for self-assessment of pubertal onset was evaluated according to sensitivity, specificity, positive predictive value and negative predictive value.

Results: A total of 174 participants (including 82 girls and 92 boys) were assessed consecutively. Correlation coefficients were 0.872 for pubic hair and 0.933 for testicular volume (<0.001) among boys; a similar result was obtained for the weighted value (0.825). For girls, the correlation coefficient and weighted for pubic hair was 0.785 and 0.878, respectively. However, breast self-assessment had a medium level of agreement with pediatrician assessment (weighted , 0.495; correlation coefficient, 0.643). Moreover, the accuracy of self-assessment in children aged 10 years or above was better than that in children aged less than 10 years.

Interpretation: Assessment of pubertal development using a web-based self-assessment instrument could be less accurate among children aged less than 10 years, especially for girls' breast assessment. Therefore, self-assessment of pubertal development, especially for breast development, should be interpreted cautiously.
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http://dx.doi.org/10.1002/ped4.12050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331344PMC
September 2018

Thermogravimetric analysis, kinetic study, and pyrolysis-GC/MS analysis of 1,1'-azobis-1,2,3-triazole and 4,4'-azobis-1,2,4-triazole.

Chem Cent J 2018 Mar 1;12(1):22. Epub 2018 Mar 1.

School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China.

Background: In general, the greater the number of directly linked nitrogen atoms in a molecule, the better its energetic performance, while the stability will be accordingly lower. But 1,1'-azobis-1,2,3-triazole (1) and 4,4'-azobis-1,2,4-triazole (2) show remarkable properties, such as high enthalpies of formation, high melting points, and relatively high stabilities. In order to rationalize this unexpected behavior of the two compounds, it is necessary to study their thermal decompositions and pyrolyses. Although a great deal of research has been focused on the synthesis and characterization of energetic materials with 1 and 2 as the backbone, a complete report on their fundamental thermodynamic parameters and thermal decomposition properties has not been published.

Methods: Thermogravimetric-differential scanning calorimetry were used to obtain the thermal decomposition data of the title compounds. Kissinger and Ozawa-Doyle methods, the two selected non-isothermal methods, are presented for analysis of the solid-state kinetic data. Pyrolysis-gas chromatography/mass spectrometry was used to study the pyrolysis process of the title compounds.

Results: The DSC curves show that the thermal decompositions of 1 and 2 are at different heating rates involved a single exothermic process. The TG curves provide insight into the total weight losses from the compounds associated with this process. At different pyrolysis temperatures, the compositions and types of the pyrolysis products differ greatly and the pyrolysis reaction at 500 °C is more thorough than 400 °C.

Conclusions: Apparent activation energies (E) and pre-exponential factors (lnA/s) are 291.4 kJ mol and 75.53 for 1; 396.2 kJ mol and 80.98 for 2 (Kissinger). The values of E are 284.5 kJ mol for 1 and 386.1 kJ mol for 2 (Ozawa-Doyle). The critical temperature of thermal explosion (T ) is evaluated as 187.01 °C for 1 and 282.78 °C for 2. The title compounds were broken into small fragment ions under the pyrolysis conditions, which then might undergo a multitude of collisions and numerous other reactions, resulting in the formation of CN (m/z 52), etc., before being analyzed by the GC/MS system.
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http://dx.doi.org/10.1186/s13065-018-0381-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833888PMC
March 2018

Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation.

J Lipid Res 2017 11 19;58(11):2147-2161. Epub 2017 Aug 19.

Department of Nutrition, University of Oslo, Oslo, Norway

Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from mice contain reduced content of LDs and accumulate less oleic acid (OA) in triacylglycerol (TAG) due to elevated LD hydrolysis in comparison with myotubes. The reduced ability to store TAG in LDs in myotubes is accompanied by a shift in energy metabolism. myotubes are characterized by increased oxidation of OA, lower glycogen synthesis, and reduced glucose oxidation in comparison with myotubes, perhaps reflecting competition between FAs and glucose as part of the Randle cycle. In accord with these metabolic changes, myotubes have elevated expression of and , transcription factors that stimulate expression of genes important for FA oxidation, whereas genes involved in glucose uptake and oxidation are suppressed. Loss of had no impact on insulin-stimulated Akt phosphorylation. Our results suggest that Plin2 is essential for protecting the pool of skeletal muscle LDs to avoid an uncontrolled hydrolysis of stored TAG and to balance skeletal muscle energy metabolism.
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http://dx.doi.org/10.1194/jlr.M079764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665670PMC
November 2017

Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies.

Eur J Endocrinol 2017 Aug 31;177(2):195-205. Epub 2017 May 31.

Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin, China.

Objective: We assessed the efficacy and safety of a weekly pegylated human growth hormone (PEG-rhGH) (Jintrolong) vs daily rhGH for children with growth hormone deficiency (GHD).

Design: Phase II and III, multicenter, open-label, randomized controlled trials.

Methods: 108 and 343 children with treatment-naive GHD from 6 hospitals in China were enrolled in the phase II and III studies respectively. Patients in the phase II study were randomized 1:1:1 to weekly Jintrolong (0.1 mg/kg/week PEG-rhGH complex), weekly Jintrolong (0.2 mg/kg/week PEG-rhGH complex) or daily rhGH (0.25 mg/kg/week) for 25 weeks. Patients in the phase III study were randomized in a 2:1 ratio to weekly Jintrolong (0.2 mg/kg/week) or daily rhGH (0.25 mg/kg/week) for 25 weeks. The primary endpoint for both studies was height velocity (HV) increase at the end of treatment. Other growth-related parameters, safety and compliance were also monitored.

Results: The phase II study established the preliminary efficacy, safety and recommended dose of Jintrolong PEG-rhGH. In the phase III study, we demonstrated significantly greater HV increases in patients receiving Jintrolong treatment (from 2.26 ± 0.87 cm/year to 13.41 ± 3.72 cm/year) vs daily rhGH (from 2.25 ± 0.82 cm/year to 12.55 ± 2.99 cm/year) at the end of treatment ( < 0.05). Additionally, significantly greater improvement in the height standard deviation scores was associated with Jintrolong throughout the treatment ( < 0.05). Adverse event rates and treatment compliance were comparable between the two groups.

Conclusion: Jintrolong PEG-rhGH at a dose of 0.2 mg/kg/week for 25 weeks is effective and safe for GHD treatment and is non-inferior to daily rhGH.
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http://dx.doi.org/10.1530/EJE-16-0905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488390PMC
August 2017

A large-scale quantitative EM study on activation of olfactory glands shows no effect of cholinergic agents.

Microscopy (Oxf) 2016 10 26;65(5):438-443. Epub 2016 Jul 26.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Little is known about olfactory glands' regulation despite their presumed importance for normal functioning of the cilia of olfactory neurons. The aim of this study was to establish an assay for olfactory gland activation by using large-scale quantitative electron microscopy (EM). In addition we wanted to test the hypothesis that cholinergic drugs activate the olfactory glands, by using our newly established EM assay. In total, over 70 000 secretory gland vesicles were quantified in over 3000 cells. Olfactory gland cell size (40.8 µm ± 2.0 SD), vesicle diameter (812 nm ± 57 SD) and vesicles per cell (21.6 ± 4.2 SD) were also quantified. The vesicle percentage of the cell area varied between 24% and 30%. In a blinded study we found no significant effects of cholinergic agents on parameters of vesicle number or vesicle diameter. Unexpectedly, pilocarpine treatment increased olfactory gland size, probably by inducing cell swelling. In conclusion, we have established a quantitative EM assay for olfactory gland activation and provided new data on basic olfactory gland cell characteristics. By using the EM assay, olfactory glands are shown not to be activated by cholinergic agents, which indicates an alternative regulation pathway or constitutive secretion from olfactory glands.
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http://dx.doi.org/10.1093/jmicro/dfw028DOI Listing
October 2016

Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention.

Physiol Rep 2014 Nov 20;2(11). Epub 2014 Nov 20.

Department of Nutrition, Institute of Basic Medical Science, University of Oslo, Oslo, Norway.

Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12-week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real-time PCR of mRNA of lipid droplet-associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large-scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training.
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http://dx.doi.org/10.14814/phy2.12187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255802PMC
November 2014

Proteome analysis and conditional deletion of the EAAT2 glutamate transporter provide evidence against a role of EAAT2 in pancreatic insulin secretion in mice.

J Biol Chem 2014 Jan 26;289(3):1329-44. Epub 2013 Nov 26.

From The Neurotransporter Group, Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.

Islet function is incompletely understood in part because key steps in glutamate handling remain undetermined. The glutamate (excitatory amino acid) transporter 2 (EAAT2; Slc1a2) has been hypothesized to (a) provide islet cells with glutamate, (b) protect islet cells against high extracellular glutamate concentrations, (c) mediate glutamate release, or (d) control the pH inside insulin secretory granules. Here we floxed the EAAT2 gene to produce the first conditional EAAT2 knock-out mice. Crossing with Nestin-cyclization recombinase (Cre) eliminated EAAT2 from the brain, resulting in epilepsy and premature death, confirming the importance of EAAT2 for brain function and validating the genetic construction. Crossing with insulin-Cre lines (RIP-Cre and IPF1-Cre) to obtain pancreas-selective deletion did not appear to affect survival, growth, glucose tolerance, or β-cell number. We found (using TaqMan RT-PCR, immunoblotting, immunocytochemistry, and proteome analysis) that the EAAT2 levels were too low to support any of the four hypothesized functions. The proteome analysis detected more than 7,000 islet proteins of which more than 100 were transporters. Although mitochondrial glutamate transporters and transporters for neutral amino acids were present at high levels, all other transporters with known ability to transport glutamate were strikingly absent. Glutamate-metabolizing enzymes were abundant. The level of glutamine synthetase was 2 orders of magnitude higher than that of glutaminase. Taken together this suggests that the uptake of glutamate by islets from the extracellular fluid is insignificant and that glutamate is intracellularly produced. Glutamine synthetase may be more important for islets than assumed previously.
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http://dx.doi.org/10.1074/jbc.M113.529065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894318PMC
January 2014

The rates of postmortem proteolysis of glutamate transporters differ dramatically between cells and between transporter subtypes.

J Histochem Cytochem 2012 Nov 2;60(11):811-21. Epub 2012 Aug 2.

Department 3 E.N.T., 1st Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Glutamate transporters (GLT-1, GLAST, EAAC1) limit the actions of excitatory amino acids. Because a disturbed transporter operation can cause or aggravate neurological diseases, transporters are of considerable neuropathological interest. Human samples, however, are seldom obtained fresh. Here, we used mice brains to study how fast glutamate transporters are degraded after death. Immunoblots showed that terminal GLT-1 epitopes (within residues 1-26 and 518-573) had mostly disappeared after 24 hr. GLAST termini (1-25 and 522-543) degraded slightly slower. In contrast, epitopes within central parts of GLT-1 (493-508) and the EAAC1 C-terminus (510-523) were readily detectable after 72 hr. The decline in immunoreactivity of the GLT-1 and GLAST termini was also seen in tissue sections, but proteolysis did not happen synchronously in all cells. At 24 hr, scattered cells remained strongly immunopositive, while the majority of cells were completely immunonegative. GLAST and GLT-1 co-localized in neocortical tissue, but at 12 hr, many GLAST-positive cells had lost the GLT-1 termini. The uneven disappearance of labeling was not observed with the antibodies to GLT-1 residues 493-508. The immunoreactivity to this epitope correlated better with the reported glutamate uptake activity. Thus, postmortem delay may affect epitopes differently, possibly causing erroneous conclusions about relative expression levels.
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http://dx.doi.org/10.1369/0022155412458589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524567PMC
November 2012

Synthesis and characterization of 5-nitro-2-nitratomethyl-1,2,3,4-tetrazole: a high nitrogen energetic compound with good oxygen balance.

Molecules 2012 May 3;17(5):5040-9. Epub 2012 May 3.

School of Material Science & Engineering, State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081, China.

The synthesis of 5-nitro-2-nitratomethyl-1,2,3,4-tetrazole (4) and its full characterization are given here. Compound 4 was synthesized through the nitration of 5-nitro-2-hydroxymethyl-tetrazole (3) with fuming nitric acid and acetic anhydride and its structure was characterized by MS, FT-IR, ¹H-NMR and ¹³C-NMR techniques. The crystal structure of 4 was determined by X-ray single crystal diffraction analysis. The compound belongs to the orthorhombic system with space group Pna2(1), and its crystal parameters were a = 2.121(8) nm, b = 0.5281(19) nm, c = 0.6246(2) nm, Z = 4, V = 0.6995(4) nm³, Dc = 1.805 g/cm³, F(000) = 384, μ = 0.174 mm⁻¹. A theoretical study of 4 has been performed, using quantum computational density functional theory (B3LYP methods) with 6-31G* basis sets as implemented in the Gaussian 03 program suite. The obtained heat of formation (HOF) for 4 was 228.07 kJ·mol⁻¹, the detonation pressure (P) values calculated for 4 was 37.92 GPa, the detonation velocity (D) can reach 9260 m·s⁻¹, and the oxygen balance was zero (Q), making 4 a competitive energetic compound.
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http://dx.doi.org/10.3390/molecules17055040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269010PMC
May 2012

[Numerical analysis of morphological variation of germplasm resources of Chrysanthemum morifolium for medicine].

Zhongguo Zhong Yao Za Zhi 2011 May;36(10):1261-5

Institute of Chinese Medicinal Materials, Nanjing Agricultural University, Nanjing 210095, China.

Objective: Botanical characters of germplasm resources of Chrysanthemum morifolium for medicine were observed and compared, which could offer reference for its genetic improvement and germplasm resources protection.

Method: Based on the random blocks field experiments design, twenty-six morphological traits were observed. The morphological differences among germplasm resources were compared by principal component analysis and cluster analysis.

Result: The coefficient of variation values for 17 of 26 traits indicated a high level of variation (above 20%). Six principal components which accounted for 77.14% of total variance were extracted from the principal component analysis. The 29 germplasm resources could be divided into two clusters.

Conclusion: There were large morphological variation among germplasm resources on Ch. morifolium for medicine.
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May 2011

Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

PLoS One 2011 Apr 29;6(4):e19260. Epub 2011 Apr 29.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6) CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019260PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084797PMC
April 2011

A case-control study of obstructive sleep apnea-hypopnea syndrome in obese and nonobese chinese children.

Chest 2008 Mar 15;133(3):684-9. Epub 2008 Jan 15.

Respiratory Department, Beijing Children's Hospital, Capital University of Medical Sciences, Beijing, People's Republic of China.

Background: Obesity is a risk factor for obstructive sleep apnea-hypopnea syndrome (OSAHS) in adults. However, the prevalence of OSAHS in children is not clear, and the relationship between obesity and OSAHS remains controversial.

Methods: Obese children were recruited from the endocrinology, respiratory, and ear, nose, and throat clinics. Weight-matched, age-matched, and sex-matched children were recruited as control subjects. Standard questionnaires were administered, and a standardized physical examination was carried out. Lateral neck roentgenography, sleep polysomnography, full blood count, and arterial blood gas analysis were also performed. Children with body mass index z-scores of > 1.96 were considered to be obese. An adenoidal/nasopharygeal ratio of > 0.67 was considered to constitute adenotonsillar hypertrophy (ATH). OSAHS was defined as an apnea-hypopnea index (AHI) score of > 5 or obstructive apnea index (OAI) score of > 1.

Results: Ninety-nine obese children and 99 control subjects were recruited into the study. Obese patients had significantly higher AHI and OAI scores, and lower sleep efficiency and minimum arterial oxygen saturation (MinSao(2)) than control subjects. The prevalence of OSAHS was significantly higher in obese children with or without the ATH groups than their nonobese counterparts (odds ratio, 1.9 vs 108, respectively; 95% confidence interval, 1.21 to 4.7 vs 6.2 to 191, respectively). Obesity, tonsillar hypertrophy, and adenoid hypertrophy were independent risk factors for OSAHS (p < 0.001, p = 0.042, and p = 0.004, respectively). There was a positive correlation between the degree of obesity and AHI (r = 0.535; p < 0.001), and an inverse correlation between obesity and MinSao(2) (r = -0.507; p < 0.001). End-tidal CO(2), Paco(2), and bicarbonate levels were within the normal range.

Conclusions: Obesity is a risk factor for OSAHS, and the degree of obesity is positively correlated with the severity of OSAHS.
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http://dx.doi.org/10.1378/chest.07-1611DOI Listing
March 2008

Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine.

Vaccine 2006 Feb 12;24(7):1028-34. Epub 2005 Sep 12.

Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Fengtai District, Beijing, PR China.

Background: In 2003, severe acute respiratory syndrome (SARS) resulted in hundreds of infections and deaths globally. We aim to assess immunogenicity and protective efficacy of purified inactivated Vero-cell SARS vaccine in monkeys.

Methods: The cultures of SARS coronavirus (SARS-CoV) BJ-01 strain infected Vero cells were inactivated with beta-propiolactone. Sequential procedures, including ultrafiltration, gel filtration and ion exchange chromatography, were performed to obtain purified inactivated SARS vaccine. The purified SARS vaccine was analyzed with electron microscope, HPLC and Western blotting. We immunized three groups of cynomolgus macaques fascicularis with adjuvant-containing purified vaccine, purified vaccine and unpurified vaccine, respectively, and a fourth group served as a control. Antibody titers were measured by plaque reduction neutralization test. The vaccinated monkeys were challenged with SARS-CoV BJ-01 strain to observe protective efficacy. Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2mug/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. We assessed the safety of the SARS vaccine and observed whether the antibody dependent enhancement (ADE) occurred under low levels of neutralizing antibody in rhesus.

Findings: The purity of SARS vaccine was 97.6% by HPLC identification and reacted with convalescent sera of SARS patients. The purified SARS vaccine induced high levels of neutralizing antibodies and prevented the replication of SARS-CoV in monkeys. Under low levels of neutralizing antibody, no exacerbation of clinical symptoms was observed when the immunized monkeys were challenged with SARS-CoV. In this preliminary animal trial, no side effects were detected when monkeys were immunized with purified SARS vaccine either at normal or large doses.

Interpretation: The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.
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http://dx.doi.org/10.1016/j.vaccine.2005.06.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115602PMC
February 2006