Publications by authors named "Qiuyue Chen"

64 Publications

A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation.

Nat Commun 2021 05 11;12(1):2697. Epub 2021 May 11.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen's allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.
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http://dx.doi.org/10.1038/s41467-021-23036-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113585PMC
May 2021

CCL2 regulation of MST1-mTOR-STAT1 signaling axis controls BCR signaling and B-cell differentiation.

Cell Death Differ 2021 Apr 20. Epub 2021 Apr 20.

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Chemokines are important regulators of the immune system, inducing specific cellular responses by binding to receptors on immune cells. In SLE patients, decreased expression of CCL2 on mesenchymal stem cells (MSC) prevents inhibition of B-cell proliferation, causing the characteristic autoimmune phenotype. Nevertheless, the intrinsic role of CCL2 on B-cell autoimmunity is unknown. In this study using Ccl2 KO mice, we found that CCL2 deficiency enhanced BCR signaling by upregulating the phosphorylation of the MST1-mTORC1-STAT1 axis, which led to reduced marginal zone (MZ) B cells and increased germinal center (GC) B cells. The abnormal differentiation of MZ and GC B cells were rescued by in vivo inhibition of mTORC1. Additionally, the inhibition of MST1-mTORC1-STAT1 with specific inhibitors in vitro also rescued the BCR signaling upon antigenic stimulation. The deficiency of CCL2 also enhanced the early activation of B cells including B-cell spreading, clustering and signalosome recruitment by upregulating the DOCK8-WASP-actin axis. Our study has revealed the intrinsic role and underlying molecular mechanism of CCL2 in BCR signaling, B-cell differentiation, and humoral response.
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http://dx.doi.org/10.1038/s41418-021-00775-2DOI Listing
April 2021

Towards knowledge-driven breeding.

Nat Plants 2021 03;7(3):242-243

State Key Laboratory of Plant Physiology and Biochemistry, National Maize Improvement Center, Key Laboratory of Biology and Genetic Improvement of Maize (MOA), Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing, China.

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http://dx.doi.org/10.1038/s41477-021-00864-7DOI Listing
March 2021

Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14 monocytes.

iScience 2021 Mar 12;24(3):102187. Epub 2021 Feb 12.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.

Dysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14 monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14 monocytes triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.
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http://dx.doi.org/10.1016/j.isci.2021.102187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879101PMC
March 2021

Structural Insight Into the SARS-CoV-2 Nucleocapsid Protein C-Terminal Domain Reveals a Novel Recognition Mechanism for Viral Transcriptional Regulatory Sequences.

Front Chem 2020 12;8:624765. Epub 2021 Jan 12.

Guangdong Provincial Key Laboratory of Biomedical Imaging, Molecular Imaging Center, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

Coronavirus disease 2019 (COVID-19) has caused massive disruptions to society and the economy, and the transcriptional regulatory mechanisms behind the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are poorly understood. Herein, we determined the crystal structure of the SARS-CoV-2 nucleocapsid protein C-terminal domain (CTD) at a resolution of 2.0 Å, and demonstrated that the CTD has a comparable distinct electrostatic potential surface to equivalent domains of other reported CoVs, suggesting that the CTD has novel roles in viral RNA binding and transcriptional regulation. Further biochemical assays demonstrated that the viral genomic intergenic transcriptional regulatory sequences (TRSs) interact with the SARS-CoV-2 nucleocapsid protein CTD with a flanking region. The unpaired adeno dinucleotide in the TRS stem-loop structure is a major determining factor for their interactions. Taken together, these results suggested that the nucleocapsid protein CTD is responsible for the discontinuous viral transcription mechanism by recognizing the different patterns of viral TRS during transcription.
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http://dx.doi.org/10.3389/fchem.2020.624765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835709PMC
January 2021

Harnessing Knowledge from Maize and Rice Domestication for New Crop Breeding.

Mol Plant 2021 01 11;14(1):9-26. Epub 2020 Dec 11.

State Key Laboratory of Plant Physiology and Biochemistry, National Maize Improvement Center, Key Laboratory of Biology and Genetic Improvement of Maize (MOA), Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing 100193, China. Electronic address:

Crop domestication has fundamentally altered the course of human history, causing a shift from hunter-gatherer to agricultural societies and stimulating the rise of modern civilization. A greater understanding of crop domestication would provide a theoretical basis for how we could improve current crops and develop new crops to deal with environmental challenges in a sustainable manner. Here, we provide a comprehensive summary of the similarities and differences in the domestication processes of maize and rice, two major staple food crops that feed the world. We propose that maize and rice might have evolved distinct genetic solutions toward domestication. Maize and rice domestication appears to be associated with distinct regulatory and evolutionary mechanisms. Rice domestication tended to select de novo, loss-of-function, coding variation, while maize domestication more frequently favored standing, gain-of-function, regulatory variation. At the gene network level, distinct genetic paths were used to acquire convergent phenotypes in maize and rice domestication, during which different central genes were utilized, orthologous genes played different evolutionary roles, and unique genes or regulatory modules were acquired for establishing new traits. Finally, we discuss how the knowledge gained from past domestication processes, together with emerging technologies, could be exploited to improve modern crop breeding and domesticate new crops to meet increasing human demands.
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http://dx.doi.org/10.1016/j.molp.2020.12.006DOI Listing
January 2021

STAT3 couples with 14-3-3σ to regulate BCR signaling, B-cell differentiation, and IgE production.

J Allergy Clin Immunol 2021 May 9;147(5):1907-1923.e6. Epub 2020 Oct 9.

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: STAT3 or dedicator of cytokinesis protein 8 (Dock8) loss-of-function (LOF) mutations cause hyper-IgE syndrome. The role of abnormal T-cell function has been extensively investigated; however, the contribution of B-cell-intrinsic dysfunction to elevated IgE levels is unclear.

Objective: We sought to determine the underlying molecular mechanism of how STAT3 regulates B-cell receptor (BCR) signaling, B-cell differentiation, and IgE production.

Methods: We used samples from patients with STAT3 LOF mutation and samples from the STAT3 B-cell-specific knockout (KO) mice Mb1Stat3 mice (B-STAT3 KO) to investigate the mechanism of hyper-IgE syndrome.

Results: We found that the peripheral B-cell homeostasis in B-STAT3 KO mice mimicked the phenotype of patients with STAT3 LOF mutation, having decreased levels of follicular and germinal center B cells but increased levels of marginal zone and IgE B cells. Furthermore, B-STAT3 KO B cells had reduced BCR signaling following antigenic stimulation owing to reduced BCR clustering and decreased accumulation of Wiskott-Aldrich syndrome protein and F-actin. Excitingly, a central hub protein, 14-3-3σ, which is essential for the increase in IgE production, was enhanced in the B cells of B-STAT3 KO mice and patients with STAT3 LOF mutation. The increase of 14-3-3σ was associated with increased expression of the upstream mediator, microRNA146A. Inhibition of 14-3-3σ with R18 peptide in B-STAT3 KO mice rescued the BCR signaling, follicular, germinal center, and IgE B-cell differentiation to the degree seen in wild-type mice.

Conclusions: Altogether, our study has established a novel regulatory pathway of STAT3-miRNA146A-14-3-3σ to regulate BCR signaling, peripheral B-cell differentiation, and IgE production.
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http://dx.doi.org/10.1016/j.jaci.2020.09.033DOI Listing
May 2021

[Application of transcranial Doppler in prognosis assessment of nerve function in patients with acute cerebral infarction after intracranial mechanical thrombectomy].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Jul;32(7):835-839

Department of Neurology, Taizhou Central Hospital (Affiliated Hospital of Taizhou University), Taizhou 318000, Zhejiang, China. Corresponding author: Chen Qiuyue, Email:

Objective: To investigate the application value of transcranial Doppler (TCD) in the prognosis assessment of nerve function in patients with acute cerebral infarction (ACI) after intracranial mechanical thrombectomy.

Methods: A retrospective analysis was conducted. The clinical data of 43 patients with acute anterior circulation cerebral infarction who received intra-arterial mechanical thrombotomy for recanalization admitted to Taizhou Central Hospital from January 2018 to December 2019 were analyzed. The modified Rankin scale (mRS) score of patients were followed up by telephone at 3 months after surgery to evaluate the prognosis of neurologic outcome. Patients with mRS score 0-2 were enrolled in the good prognosis group, while those with a score of 3-6 were enrolled in the poor prognosis group. The gender, age, past history, underlying diseases, occluded arteries, atherosclerotic stenosis and bridging treatment, time from onset to reperfusion, blood flow dynamics under TCD at 1 day after thrombectomy, and National Institutes of Health stroke scale (NIHSS) scores before and 1, 7, and 14 days after thrombectomy were compared between the two groups. Multivariate Logistic regression analysis was used to screen the prognostic factors of nerve function at 3 months after mechanical thrombectomy in patients with ACI. The receiver operating characteristic (ROC) curve was drawn to evaluate the prognostic value for neurological function assessed by TCD.

Results: Forty-three patients were enrolled in the final analysis, with 23 patients in the good prognosis group and 20 in the poor prognosis group. The recanalization was successfully achieved in both groups without complications. However, the hemodynamics of intracranial arteries evaluated by TCD 1 day after operation in both groups still showed partial or complete occlusion, and the hemodynamics of patients in the poor prognosis group was worse than that in the good prognosis group (poor blood flow: 40.0% vs. 0%, inadequate blood flow: 30.0% vs. 17.4%, good blood flow: 30.0% vs. 82.6%), and the differences were statistically significant (all P < 0.01). Before thrombotomy, there was no significant difference in NIHSS score between the two groups. After thrombotomy, the NIHSS score of the two groups gradually decreased with the extension of time, but the NIHSS score at 14 days after operation of the poor prognosis group was still significantly higher than that of the good prognosis group (10.55±2.93 vs. 4.65±1.70, P < 0.01). Univariate analysis showed that compared with the good prognosis group, the proportion of patients with diabetes and arteriosclerosis stenosis in the poor prognosis group were significantly increased (30.0% vs. 4.3%, 45.0% vs. 17.4%, both P < 0.05), and the time from onset to reperfusion was prolonged (minutes: 385.9±96.2 vs. 294.5±95.1, P < 0.01). Multivariable Logistic regression analysis showed that the therosclerosis stenosis [odds ratio (OR) = 9.334, 95% confidence interval (95%CI) was 1.092-79.775, P = 0.041] and the reperfusion time (OR = 1.016, 95%CI was 1.006-1.027, P = 0.002) were associated with prognosis of nerve function at 3 months after mechanical thrombectomy in patients with ACI. ROC curve analysis suggested that the evaluation of intracranial hemodynamics by TCD might be able to predict the prognosis of neurological function in patients with ACI after 3 months of intracranial mechanical thrombectomy, the area under ROC curve (AUC) was 0.768 (95%CI was 0.620-0.917), the sensitivity was 65.0%, the specificity was 87.0%, the positive predictive value was 82.6%, and the negative predictive value was 70.0%.

Conclusions: The evaluation of intracranial hemodynamics assessed by TCD is helpful in early judging the prognosis of neurological function in patients with ACI after intracranial mechanical thrombectomy.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200410-00281DOI Listing
July 2020

DOCK2 couples with LEF-1 to regulate B cell metabolism and memory response.

Biochem Biophys Res Commun 2020 08 29;529(2):296-302. Epub 2020 Jun 29.

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Dedicator of cytokinesis 2 (DOCK2) is essential for the B cell differentiation, BCR signaling and humoral immune response. However, the role of DOCK2 in the memory response of B cell is unknown. By using two DOCK2 deficient patients, we found that the memory B cells were decreased and the early activation of DOCK2 deficient memory B cells was abolished to the degree of naïve B cells due to the decreased expression of CD19 and CD21 mechanistically. Interestingly the expression of LEF-1, a negative regulator of CD21, was increased in DOCK2 deficient B cells. This was linked to the increased expression of HIF-1α and cell metabolism, which in turn affected the ER structure. Finally, the reduction of memory B cells in DOCK2 patients was due to the increased apoptosis, which might be related with the increased metabolism.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.152DOI Listing
August 2020

Transcriptomic and proteomic analyses of ovarian follicles reveal the role of VLDLR in chicken follicle selection.

BMC Genomics 2020 Jul 16;21(1):486. Epub 2020 Jul 16.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian, China.

Background: Follicle selection in chickens refers to the process of selecting one follicle from a group of small yellow follicles (SY, 6-8 mm in diameter) for development into 12-15 mm hierarchical follicles (usually F6 follicles), which is an important process affecting laying performance in the poultry industry. Although transcriptomic analysis of chicken ovarian follicles has been reported, integrated analysis of chicken follicles for selection by using both transcriptomic and proteomic approaches is still rarely performed. In this study, we compared the proteomes and transcriptomes of SY and F6 follicles in laying hens and identified several genes involved in chicken follicle selection.

Results: Transcriptomic analysis revealed 855 differentially expressed genes (DEGs) between SY follicles and F6 follicles in laying hens, among which 202 were upregulated and 653 were downregulated. Proteomic analysis revealed 259 differentially expressed proteins (DEPs), including 175 upregulated and 84 downregulated proteins. Among the identified DEGs and DEPs, changes in the expression of seven genes, including VLDLR1, WIF1, NGFR, AMH, BMP15, GDF6 and MMP13, and nine proteins, including VLDLR, VTG1, VTG3, PSCA, APOB, APOV1, F10, ZP2 and ZP3L2, were validated. Further analysis indicated that the mRNA level of chicken VLDLR was higher in F6 follicles than in SY follicles and was also higher in granulosa cells (GCs) than in thecal cells (TCs), and it was stimulated by FSH in GCs.

Conclusions: By comparing the proteomes and transcriptomes of SY and F6 follicles in laying hens, we identified several differentially expressed proteins/genes that might play certain roles in chicken follicle selection. These data may contribute to the identification of functional genes and proteins involved in chicken follicle selection.
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http://dx.doi.org/10.1186/s12864-020-06855-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367319PMC
July 2020

The genetic architecture of the maize progenitor, teosinte, and how it was altered during maize domestication.

PLoS Genet 2020 05 14;16(5):e1008791. Epub 2020 May 14.

Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

The genetics of domestication has been extensively studied ever since the rediscovery of Mendel's law of inheritance and much has been learned about the genetic control of trait differences between crops and their ancestors. Here, we ask how domestication has altered genetic architecture by comparing the genetic architecture of 18 domestication traits in maize and its ancestor teosinte using matched populations. We observed a strongly reduced number of QTL for domestication traits in maize relative to teosinte, which is consistent with the previously reported depletion of additive variance by selection during domestication. We also observed more dominance in maize than teosinte, likely a consequence of selective removal of additive variants. We observed that large effect QTL have low minor allele frequency (MAF) in both maize and teosinte. Regions of the genome that are strongly differentiated between teosinte and maize (high FST) explain less quantitative variation in maize than teosinte, suggesting that, in these regions, allelic variants were brought to (or near) fixation during domestication. We also observed that genomic regions of high recombination explain a disproportionately large proportion of heritable variance both before and after domestication. Finally, we observed that about 75% of the additive variance in both teosinte and maize is "missing" in the sense that it cannot be ascribed to detectable QTL and only 25% of variance maps to specific QTL. This latter result suggests that morphological evolution during domestication is largely attributable to very large numbers of QTL of very small effect.
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http://dx.doi.org/10.1371/journal.pgen.1008791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266358PMC
May 2020

Correction to: CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling.

Cell Mol Life Sci 2020 Nov;77(21):4441-4447

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

In the original published version of the article, the red squares in the figures which indicated the corrections.
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http://dx.doi.org/10.1007/s00018-020-03501-2DOI Listing
November 2020

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites.

Acta Pharm Sin B 2020 Jul 20;10(7):1228-1238. Epub 2020 Apr 20.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
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http://dx.doi.org/10.1016/j.apsb.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194921PMC
July 2020

HBV DNA integrates into upregulated ZBTB20 in patients with hepatocellular carcinoma.

Mol Med Rep 2020 Jul 16;22(1):380-386. Epub 2020 Apr 16.

Department of Neurology, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, Zhejiang 318000, P.R. China.

Hepatitis B virus (HBV) affects the malignant phenotype of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the integration sites of HBV DNA and the expression of the zinc finger protein, zinc finger and BTB domain containing 20 (ZBTB20) in patients with hepatocellular carcinoma. Integration of the HBV gene was detected using a high‑throughput sequencing technique based on the HBV‑Alu‑PCR method. The expression of ZBTB20 was detected by western blotting. HBVX integration sites were detected in ~70% of the HCC tissue samples. HBV‑integrated subgene X detection suggested that 67% of the integrated specimens were inserted into the host X gene in a forward direction, 57% in a reverse direction, 24% in both forward and reverse directions, and 38% had two HBV integration sites. A total of 3,320 HBV integration sites were identified, including 1,397 in HCC tissues, 1,205 in paracancerous tissues and 718 in normal liver tissues. HBV integration fragments displayed enrichment in the 200‑800 bp region. Additionally, the results suggested that HBV was highly integrated into transmembrane phosphatase with tensin homology, long intergenic non‑protein coding RNA (LINC)00618, LOC101929241, ACTR3 pseudogene 5, LINC00999, LOC101928775, deleted in oesophageal cancer 1, LINC00824, EBF transcription factor 2 and ZBTB20 in tumour tissues. Furthermore, the expression of ZBTB20 was upregulated in HCC tissues compared with normal control liver tissues, and was associated with HBV integration frequency. The present study suggested that HBV DNA integrated into upregulated ZBTB20 in patients with hepatocellular carcinoma, which might promote the occurrence and development of HCC. Furthermore, the results of the present study may provide a theoretical basis for the diagnosis and treatment of HCC.
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http://dx.doi.org/10.3892/mmr.2020.11074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248478PMC
July 2020

Epigenetic changes associated with increased estrogen receptor alpha mRNA transcript abundance during reproductive maturation in chicken ovaries.

Anim Reprod Sci 2020 Mar 18;214:106287. Epub 2020 Jan 18.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, PR China. Electronic address:

Estrogen receptor alpha (ERα) is a ligand-activated transcription factor that regulates cellular responses to estrogens and transcription processes of target genes. In this study, changes in DNA methylation and histone modifications in the promoter region and Exon 1 of the ERα gene were analyzed to ascertain epigenetic changes associated with increased ERα mRNA abundance during reproductive maturation from 90 (egg production not yet initiated) to 160 (after egg production was initiated) d of age (d post-hatching) in chicken ovaries. The results indicate there was no difference in CpG methylation at the promoter and Exon 1 except at the region analyzed with primer pairs F2 and R2, where percentage of methylated CpG of Sites 2 and 8 after reproductive maturation was greater compared with before reproductive maturation. By using the chromatin immunuoprecipitation (ChIP) assay combined with SYBR green quantitative PCR, effects of histone modifications were evaluated, including histone H3K4 di + tri methylation, H3K9 phosphorylation and trimethylation, H3K36 methylation and H3K27 acetylation on chicken ERα mRNA transcript abundance. The results indicated that there was a greater histone H3K27 acetylation and lesser H3K36 trimethylation associated with increased abundance of ERα mRNA transcript in chicken ovaries after reproductive maturation (90 compared with 160 d of age). In consistent with this finding, the relative abundance of transcriptional coactivator p300 mRNA transcript and protein in the ovaries was markedly greater in reproductively mature than immature chickens. Findings provide insights into the epigenetic regulations of the chicken ERα gene expression that is required for chicken ovarian development.
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http://dx.doi.org/10.1016/j.anireprosci.2020.106287DOI Listing
March 2020

CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling.

Cell Mol Life Sci 2020 Nov 4;77(21):4379-4395. Epub 2020 Feb 4.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

As an important chemokine receptor, the role of CX3CR1 has been studied extensively on the migration of lymphocytes including T and B cells. Although CX3CR1 B cells have immune suppressor properties, little is known about its role on the regulation of BCR signaling and B cell differentiation as well as the underlying molecular mechanism. We have used CX3CR1 KO mice to study the effect of CX3CR1 deficiency on BCR signaling and B cell differentiation. Interestingly, we found that proximal BCR signaling, such as the activation of CD19, BTK and SHIP was reduced in CX3CR1 KO B cells upon antigenic stimulation. However, the activation of mTORC signaling was enhanced. Mechanistically, we found that the reduced BCR signaling in CX3CR1 KO B cells was due to reduced BCR clustering, which is caused by the enhanced actin accumulation by the plasma membrane via increased activation of WASP. This caused an increased differentiation of MZ B cells in CX3CR1 KO mice and an enhanced generation of plasma cells (PC) and antibodies. Our study shows that CX3CR1 regulates BCR signaling via actin remodeling and affects B cell differentiation and the humoral immune response.
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http://dx.doi.org/10.1007/s00018-019-03416-7DOI Listing
November 2020

Impact of concurrent right ventricular myocardial infarction on outcomes among patients with left ventricular myocardial infarction.

Sci Rep 2020 02 3;10(1):1736. Epub 2020 Feb 3.

The Third People Hospital of Huizhou, The Affiliated Hospital of Guangzhou Medical University, Huizhou, Guangdong, China.

To compare in-hospital outcomes between left ventricular myocardial infarction (LVMI) patients with and without right ventricular myocardial infarction (RVMI). Patients with acute ST-segment elevation MI (STEMI) undergoing primary percutaneous coronary intervention (PCI) were enrolled and divided into LVMI with and without RVMI groups. Between-group differences and in-hospital outcomes were compared. Compared to patients without RVMI, patients with RVMI were more likely to be male, have higher body mass index, serum levels of C-reactive protein (8.9 ± 2.4 vs 6.2 ± 2.1 mg/dL), B-type natriuretic peptide (1295 ± 340 vs 872 ± 166 pg/mL) and cardiac troponin-I (8.6 ± 2.9 vs 5.2 ± 2.1 ng/mL), and have diabetes (36.3% vs 3.4%) and dyslipidemia (53.4% vs 48.1%). Patients with RVMI had lower left and right ventricular ejection fraction (50.5 ± 5.6% vs 53.4 ± 3.8% and 33.6 ± 2.9% vs 45.7 ± 2.0%), but had higher mean pulmonary artery pressure (30.6 ± 3.3 vs 23.8 ± 3.1 mm Hg). Compared to patients without RVMI, patients with RVMI had higher odds of in-hospital all-cause mortality (4.1% vs 1.0%) and new onset acute heart failure (3.4% vs 1.0%). After adjusted for confounding factors, LVMI with RVMI remained independently associated with composite outcomes, with odds ratio 1.66 (95% confidence interval 1.39-2.04). Compared to isolated LVMI patients, those with concomitant RVMI have higher odds of in-hospital complications, particularly all-cause mortality and new onset acute heart failure.
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http://dx.doi.org/10.1038/s41598-020-58713-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997358PMC
February 2020

TeoNAM: A Nested Association Mapping Population for Domestication and Agronomic Trait Analysis in Maize.

Genetics 2019 11 3;213(3):1065-1078. Epub 2019 Sep 3.

Laboratory of Genetics, University of Wisconsin-Madison, Wisconsin 53706

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping (TeoNAM) population, derived from crossing five teosinte inbreds to the maize inbred line W22. The resulting 1257 BCS RILs were genotyped with 51,544 SNPs, providing a high-density genetic map with a length of 1540 cM. On average, each RIL is 15% homozygous teosinte and 8% heterozygous. We performed joint linkage mapping (JLM) and a genome-wide association study (GWAS) for 22 domestication and agronomic traits. A total of 255 QTL from JLM were identified, with many of these mapping near known genes or novel candidate genes. TeoNAM is a useful resource for QTL mapping for the discovery of novel allelic variation from teosinte. TeoNAM provides the first report that , a rice domestication gene, is also a QTL associated with tillering in teosinte and maize. We detected multiple QTL for flowering time and other traits for which the teosinte allele contributes to a more maize-like phenotype. Such QTL could be valuable in maize improvement.
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http://dx.doi.org/10.1534/genetics.119.302594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827374PMC
November 2019

Teosinte ligule allele narrows plant architecture and enhances high-density maize yields.

Science 2019 08;365(6454):658-664

State Key Laboratory of Plant Physiology and Biochemistry, National Maize Improvement Center, Key Laboratory of Biology and Genetic Improvement of Maize (MOA), Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing 100193, China.

Increased planting densities have boosted maize yields. Upright plant architecture facilitates dense planting. Here, we cloned () and , two quantitative trait loci conferring upright plant architecture. is controlled by a two-base sequence polymorphism regulating the expression of a B3-domain transcription factor () located 9.5 kilobases downstream. exhibits differential binding by DRL1 (DROOPING LEAF1), and DRL1 physically interacts with LG1 (LIGULELESS1) and represses LG1 activation of regulates (), which underlies , altering endogenous brassinosteroid content and leaf angle. The allele that reduces leaf angle originated from teosinte, the wild ancestor of maize, and has been lost during maize domestication. Introgressing the wild allele into modern hybrids and editing enhance high-density maize yields.
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http://dx.doi.org/10.1126/science.aax5482DOI Listing
August 2019

Evolutionary Metabolomics Identifies Substantial Metabolic Divergence between Maize and Its Wild Ancestor, Teosinte.

Plant Cell 2019 09 21;31(9):1990-2009. Epub 2019 Jun 21.

State Key Laboratory of Plant Physiology and Biochemistry, National Maize Improvement Center, Key Laboratory of Biology and Genetic Improvement of Maize (MOA), Beijing Key Laboratory of Crop Genetic Improvement, Center for Crop Functional Genomics and Molecular Breeding, China Agricultural University, Beijing 100193, China.

Maize ( subsp ) was domesticated from its wild ancestor, teosinte ( subsp ). Maize's distinct morphology and adaptation to diverse environments required coordinated changes in various metabolic pathways. However, how the metabolome was reshaped since domestication remains poorly understood. Here, we report a comprehensive assessment of divergence in the seedling metabolome between maize and teosinte. In total, 461 metabolites exhibited significant divergence due to selection. Interestingly, teosinte and tropical and temperate maize, representing major stages of maize evolution, targeted distinct sets of metabolites. Alkaloids, terpenoids, and lipids were specifically targeted in the divergence between teosinte and tropical maize, while benzoxazinoids were specifically targeted in the divergence between tropical and temperate maize. To identify genetic factors controlling metabolic divergence, we assayed the seedling metabolome of a large maize-by-teosinte cross population. We show that the recent metabolic divergence between tropical and temperate maize tended to have simpler genetic architecture than the divergence between teosinte and tropical maize. Through integrating transcriptome data, we identified candidate genes contributing to metabolic divergence, many of which were under selection at the nucleotide and transcript levels. Through overexpression or mutant analysis, we verified the roles of , , and maize in the divergence of their related biosynthesis pathways. Our findings not only provide important insights into domestication-associated changes in the metabolism but also highlight the power of combining omics data for trait dissection.
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http://dx.doi.org/10.1105/tpc.19.00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751114PMC
September 2019

[Application of lean management in cost control of cerebral infarction single disease in stroke center].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019 May;31(5):637-640

Department of Neurology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang, China. Corresponding author: Chen Qiuyue, Email:

Objective: To explore the effect of lean management on cost control of single disease in patients with acute cerebral infarction (ACI) in stroke center.

Methods: A retrospective study was conducted. The patients with ACI who underwent intravenous thrombolysis in the stroke center of Taizhou Central Hospital in Zhejiang Province were enrolled. Thirty patients adopted traditional management procedures from July 2016 to September 2017 were enrolled in the control group, and 32 patients received lean management from October 2017 to December 2018 were enrolled in the lean group. The patients in the control group were treated with traditional intravenous thrombolysis, and the patients were sent to the neurology ward for intravenous thrombolysis. The patients in the lean group applied lean management value stream to optimize process management, the lean management team of the stroke center was established, and the green channel for stroke treatment was established to eliminate the waiting time as far as possible. The location of thrombolysis was changed from neurology ward to the neurological intensive care unit (NICU) in emergency department. The patients in the two groups were compared in terms of intravenous thrombolytic door-to-needle time (DNT), admission time to the neurologist's visit time (T1), CT examination time to neurology ward or NICU admission time (T2), neurology ward/NICU visit time to medication time (T3), and the proportion of patients with DNT controlled within 40 minutes, recovery of neurological impairment 7 days after thrombolysis [national institutes of health stroke scale (NIHSS) score], activity of daily living assessment (Barthel index), length of hospital stay, cost of hospital stay and patient satisfaction. At the same time, the main process quality and the implementation rate of easily missed indexes of cerebral infarction single disease were recorded.

Results: Compared with the control group, DNT, T1 and T2 in the lean group were significantly shortened [DNT (minutes): 39.56±11.12 vs. 63.03±19.63, T1 (minutes): 16.23±6.79 vs. 33.48±12.63, T2 (minutes): 13.45±3.84 vs. 17.47±5.56, all P < 0.01], T3 was slightly shortened (minutes: 9.88±1.95 vs. 10.95±2.69, P > 0.05), and the proportion of DNT control within 40 minutes was significantly increased [75.0% (24/32) vs. 16.7% (5/30), P < 0.01], the 7-day NIHSS score was decreased significantly (8.66±4.12 vs. 13.00±5.63, P < 0.01), 7-day Barthel index was increased significantly (71.6±16.7 vs. 54.7±17.1, P < 0.01), the length of hospital stay was significantly shortened (days: 9.69±4.06 vs. 12.47±3.83, P < 0.01), the hospital costs were significantly reduced (Yuan: 16 338±5 481 vs. 19 470±5 495, P < 0.05), the satisfaction of patients was improved significantly [(91.38±2.69)% vs. (86.53±2.78)%, P < 0.01]. In terms of the implementation rate of quality indicators such as pre-application evaluation of thrombolytic drugs, evaluation of dysphagia, and evaluation of vascular function, health education of ACI, rehabilitation evaluation and implementation within 24 hours, etc., the lean group was significantly improved as compared with the control group [(87.5% (28/32) vs. 53.3% (16/30), 96.9% (31/32) vs. 73.3% (22/30), 78.1% (25/32) vs. 43.3% (13/30), 100.0% (32/32) vs. 76.7% (23/30), 75.0% (24/32) vs. 33.3% (10/30), all P < 0.05].

Conclusions: Lean thinking can realize the standardization of stroke center process, effectively utilize medical resources, improve medical quality and reduce the cost of cerebral infarction single disease.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2019.05.023DOI Listing
May 2019

The modulation of drug-loading stability within lipid membranes via medium chain triglycerides incorporation.

Int J Pharm 2019 Jul 3;566:371-382. Epub 2019 Jun 3.

Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:

The current research aimed to explore medium chain triglycerides (MCT) incorporation in liposomes to overcome stability challenges when drugs with high molecular weight and payload are loaded within lipid membranes. A model drug clarithromycin was loaded in lipid dispersions with various MCT/phospholipids ratios (R = 0, 0.5, 1.75 and 7.5 w/w). TEM images demonstrated a liposome-to-emulsion structural transformation by MCT incorporation to cause increased particle size (104.3-167.7 nm) but decreased zeta potential (-63.6 to -44.4 mV) of lipid particles. MCT incorporation produced biphasic release in PBS and accelerated released in plasma. The tolerance of liposomes for thermal sterilization, high temperature test and freeze-thaw cycles were significantly improved by MCT incorporation. However, MCT incorporation produced adverse effects on colloidal stability in plasma and pharmacokinetics behavior in vivo to some extent. MCT stabilizing mechanism attributes to the modulation of drug loading area and stability improvement of lipid carriers. MCT incorporated liposomes achieved 2-3 fold cellular uptake level than traditional liposomes without significant cytotoxicity. These results indicated that MCT incorporation could be a promising strategy to apply in liposome production to achieve stable drug loading.
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http://dx.doi.org/10.1016/j.ijpharm.2019.06.003DOI Listing
July 2019

The Role of PTHLH in Ovarian Follicle Selection, Its Transcriptional Regulation and Genetic Effects on Egg Laying Traits in Hens.

Front Genet 2019 14;10:430. Epub 2019 May 14.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

In hens, follicle selection is an important process affecting egg laying traits. This study investigated the role of parathyroid hormone-like hormone (PTHLH) in chicken follicle selection, its transcriptional regulation and genetic effects on egg laying traits. PTHLH and its receptor PTH1R were mainly expressed in follicles of 6-8 mm in diameter, exhibits differential expression pattern in the theca and granulosa cells of pre- and hierarchal follicles. PTHLH stimulates the proliferation of follicular granulosa and theca cells, the expression of StAR and CYP11A1 mRNA and the production of progesterone (P4) in pre-hierarchal follicles. Treatment with FSH increased PTHLH mRNA expression in pre-hierarchal follicular theca cells and hierarchal follicular granulosa cells. Two critical regions regulating chicken PTHLH transcription were revealed, each of which harbored a SNP: C>T (chr1: 72530014) for AP-1 and a SNP: A>G (chr1: 72531676). Hens with diplotype AC/GT were younger at first laying and laid more eggs at 32 weeks. The haplotype (GT) with double mutations had the greatest promoter activity of chicken PTHLH transcription. Collectively, PTHLH plays an important role in chicken follicle selection by stimulating cell proliferation and steroidogenesis. Polymorphisms in chicken PTHLH promoter region are associated with egg laying traits by affecting the binding of transcription factor AP-1.
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http://dx.doi.org/10.3389/fgene.2019.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530352PMC
May 2019

DPP-4 Inhibitors as Potential Candidates for Antihypertensive Therapy: Improving Vascular Inflammation and Assisting the Action of Traditional Antihypertensive Drugs.

Front Immunol 2019 9;10:1050. Epub 2019 May 9.

Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China.

Dipeptidyl peptidase-4 (DPP-4) is an important protease that is widely expressed on the surface of human cells and plays a key role in immune-regulation, inflammation, oxidative stress, cell adhesion, and apoptosis by targeting different substrates. DPP-4 inhibitors (DPP-4i) are commonly used as hypoglycemic agents. However, in addition to their hypoglycemic effect, DPP-4i have also shown potent activities in the cardiovascular system, particularly in the regulation of blood pressure (BP). Previous studies have shown that the regulatory actions of DPP-4i in controlling BP are complex and that the mechanisms involved include the functional activities of the nerves, kidneys, hormones, blood vessels, and insulin. Recent work has also shown that inflammation is closely associated with the elevation of BP, and that the inhibition of DPP-4 can reduce BP by regulating the function of the immune system, by reducing inflammatory reactions and by improving oxidative stress. In this review, we describe the potential anti-hypertensive effects of DPP-4i and discuss potential new anti-hypertensive therapies. Our analysis indicated that DPP-4i treatment has a mild anti-hypertensive effect as a monotherapy and causes a significant reduction in BP when used in combined treatments. However, the combination of DPP-4i with high-dose angiotensin converting enzyme inhibitors (ACEI) can lead to increased BP. We suggest that DPP-4i improves vascular endothelial function in hypertensive patients by suppressing inflammatory responses and by alleviating oxidative stress. In addition, DPP-4i can also regulate BP by activating the sympathetic nervous system, interfering with the renin angiotensin aldosterone system (RAAS), regulating Na/HO metabolism, and attenuating insulin resistance (IR).
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http://dx.doi.org/10.3389/fimmu.2019.01050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526751PMC
September 2020

Cisplatin-loaded polymeric complex micelles with a modulated drug/copolymer ratio for improved in vivo performance.

Acta Biomater 2019 07 6;92:205-218. Epub 2019 May 6.

Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Shenyang 110016, China.

This study aimed to evaluate the performance of cisplatin-loaded polymeric micelles (CDDP-PMs) with different drug/copolymer ratios of 1:1, 1:3 and 1:6 (w/w) prepared by coordinated complexation and self-assembly method. The mass ratio influenced the self-assembly behaviors and the complex degree, where both single- and double- complexation existed in CDDP-PMs. With the increase of CDDP/copolymer ratio, the particle size and drug loading increased, while encapsulation efficiency decreased. The PEG density of CDDP-PM, CDDP-PM and CDDP-PM were 0.20, 0.61 and 0.38 PEG/nm, respectively. CDDP-PM and CDDP-PM had similar sustained release behavior, while CDDP-PM showed burst release. Pharmacokinetics showed the AUC of CDDP-PM, CDDP-PM and CDDP-PM was 27.2, 76.6 and 13.0 fold higher than CDDP solution. Tissue distribution presented the platinum concentration of CDDP-PM, CDDP-PM and CDDP-PM was 1.03, 0.80 and 0.48 times of CDDP solution in kidney at 10 min, and 17.61, 28.63 and 16.6 times in tumor at 48 h respectively, indicating CDDP-PMs significantly reduced nephrotoxicity and increased tumor-targeting accumulation. In vivo antitumor test showed that CDDP-PMs exhibited an improved antitumor efficacy and lower systemic toxicity compared with CDDP solution. From CDDP-PM to CDDP-PM, the toxicity decreased with the increase of copolymer ratio, but the tumor inhibition rate also decreased. CDDP-PM had relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot. This work provides an effective strategy by modulating drug/copolymer ratio of CDDP-PMs to balance the antitumor efficacy and toxicity for better payoff. STATEMENT OF SIGNIFICANCE: Cancer chemotherapy always exists a contradiction between antitumor efficacy and toxicity. Higher efficacy against tumor often associated with larger toxicity for normal tissues. This work provides an important strategy by modulating the drug/copolymer ratios to balance the antitumor efficacy and toxicity to obtain better payoff. The cisplatin-loaded polymeric micelles (CDDP-PMs) based on the complexation between CDDP and copolymer with different mass ratios make differences in vitro and in vivo because of the single- or double-complexation degree. Most importantly, we found the balance at CDDP/copolymer ratio of 1:3, which has relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot.
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http://dx.doi.org/10.1016/j.actbio.2019.05.007DOI Listing
July 2019

[Effect of intermittent high glucose on oxygen-glucose deprivation/refurnish neuronal survival].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019 Jan;31(1):61-66

Department of Public Health Unit, Taizhou Enze Medical Center Enze Hospital, Taizhou 318050, Zhejiang, China. Corresponding author: He Zebao, Email:

Objective: To investigate the effect of intermittent high glucose on oxygen-glucose deprivation/refurnish (OGD/R) neuronal survival.

Methods: The primary cultured hippocampal neurons of mice were sub-cultured when the cell fusion reached about 80%. Cells in logarithmic growth phase were placed in a hypoxic incubator (37 centigrade, 5% CO, 95% N) to simulate cell hypoxia. The culture medium was replaced by glucose-free Hank equilibrium salt solution (HBSS) to simulate cell hypoglycemia. The normal glucose and oxygen control group was set up. Cell morphology was observed under inverted phase contrast microscope after 6 hours of hypoxia and hypoglycemia treatment, and cell viability was detected by CCK-8 cell proliferation assay kit, and then grouping experiment was carried out. The cells were randomly divided into four groups. The cells were cultured in different concentration glucose medium under normal oxygen, 5% CO and 37 centigrade for 72 hours to prepare OGD/R model of cell ischemia/reperfusion. The low-glucose control group was cultured in medium containing 5.5 mmol/L glucose. The constant high-glucose group was cultured in medium containing 33.0 mmol/L glucose. The intermittent high-glucose group was cultured in medium containing 33.0 mmol/L glucose for 3 hours then in medium containing 5.5 mmol/L glucose for 2 hours alternately for 3 times during the day, and overnight in medium containing 33.0 mmol/L glucose at night. The hyperosmotic control group was made up of 5.5 mmol/L glucose medium and mannitol. The osmotic pressure was the same as that of the constant high-glucose group, and the effective glucose concentration was the same as that of the normal glucose and oxygen group, so as to eliminate the effect of osmotic pressure changes caused by the high-glucose medium on the results. Cell morphology was observed under inverted phase contrast microscope after 72 hours of cell culture in each group. Cell viability was measured by CCK-8 kit, and apoptotic rate was measured by flow cytometry.

Results: The inverted phase contrast microscope showed that the cells in the normal glucose and oxygen control group were plump and refractive, and had obvious nucleus, clear processes and high cell activity. After 6 hours of hypoxia and hypoglycemia treatment, the cells were shrunk, refractive index was poor, the nucleus was unclear, the processes were not clear, and the cell activity was significantly lower than that of normal glucose and oxygen control group (A value: 0.34±0.06 vs. 1.09±0.06, P < 0.01), which indicated that the model of oxygen-glucose deprivation (OGD) was successfully prepared. After 72 hours of culture with different concentrations of glucose, the cells in the low-glucose control group were shrunk, the cell membrane was incomplete, the nucleus was unclear, and number of necrotic cells were more. In the constant high-glucose group, the refractive index of cells was poor, a large number of cells floated, and the nucleus was not obvious. In the intermittent high-glucose group, the cell morphology was normal, the refractive rate of cells was decreased slightly, and the necrotic cells were less. In the hypertonic control group, the cell status was close to that in the constant high-glucose group. Compared with the low-glucose control group or constant high-glucose group,the cell viability in the intermittent high-glucose group was significantly increased (A value: 2.04±0.15 vs. 0.64±0.18, 1.16±0.16, both P < 0.01), the apoptotic rate was significantly decreased [(59.60±2.55)% vs. (78.15±15.77)%, (95.60±0.14)%, both P < 0.05]. There was no significant difference in cell activity or apoptotic rate between the hypertonic control group and the constant high-glucose group [cell activity (A value): 1.07±0.07 vs. 1.16±0.16, apoptotic rate: (87.80±4.53)% vs. (95.60±0.14)%, both P > 0.05].

Conclusions: Intermittent high glucose within a certain range had protective effect on OGD/R neuronal survival.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2019.01.013DOI Listing
January 2019

Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma.

Oncol Lett 2019 Feb 17;17(2):2040-2046. Epub 2018 Dec 17.

Department of Pathology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.

Oral cancer is a common cancer of the head and neck. Oral squamous cell carcinoma (OSCC) represents almost 90% of the total cases of head and neck cancer. Ubiquitin-specific protease 22 (USP22) is a deubiquitinating hydrolase, and it is highly expressed in various types of cancer, which also typically have a poor prognosis. Aurora-B and Survivin, which belong to the chromosomal passenger complex, are also highly expressed in a number of types of cancer. In the present study, USP22 expression and its associations with Aurora-B and Survivin, and the clinicopathological features in OSCC were explored. USP22 is highly expressed in OSCC. Overexpression of USP22 is associated with lymph node metastasis and histological grade (P<0.01). Additionally, the expression of USP22 was positively associated with Aurora-B (P<0.01), Survivin (P<0.01), and Ki-67 (P<0.01). Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora-B, Survivin and Cyclin B, together with the upregulation of cyclin-dependent kinase inhibitor 1A (p21). These data suggest that USP22, Aurora-B and Survivin promote the OSCC development and may represent novel targets for OSCC diagnosis and treatment in the future.
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http://dx.doi.org/10.3892/ol.2018.9837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341666PMC
February 2019

Expression dynamics of gonadotropin-releasing hormone-I and its mutual regulation with luteinizing hormone in chicken ovary and follicles.

Gen Comp Endocrinol 2019 01 16;270:96-102. Epub 2018 Oct 16.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian, PR China. Electronic address:

Gonadotropin-releasing hormone-I (GnRH-I) has been identified in the ovaries of vertebrate species, and this decapeptide is a key regulator of reproductive functions. However, its biological action and regulatory mechanism in the chicken ovary remain to be characterized. In this study, the expression of GnRH-I gene in chicken hypothalamus and ovaries at different developmental stages and different sizes of follicles was investigated, and the effect of GnRH-I mRNA on chicken follicular cells was analyzed in vitro. The results showed that the expression of GnRH-I was dramatically decreased in the hen ovary compared to that in the hypothalamus after sexual maturation. In the mature ovarian follicles, GnRH-I mRNA levels were significantly higher in theca cells than that in granulosa cells. Overexpression of GnRH-I decreased the expression of luteinizing hormone receptor (LHR) mRNA in theca cells from preovulatory follicles but had no effect on granulosa cells. Treatment of theca cells with different concentrations of luteinizing hormone (LH) significantly increased GnRH-I mRNA expression at low doses (50 ng/ml) but significantly decreased it at higher doses (200 ng/ml). Furthermore, GnRH-I inhibited LH-induced LHR expression at the lower dose of LH (50 ng/ml). These findings provide strong evidence indicating that GnRH-I is an important regulator in the chicken ovary.
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http://dx.doi.org/10.1016/j.ygcen.2018.10.011DOI Listing
January 2019

Stepwise cis-Regulatory Changes in ZCN8 Contribute to Maize Flowering-Time Adaptation.

Curr Biol 2018 09 13;28(18):3005-3015.e4. Epub 2018 Sep 13.

National Maize Improvement Center, Key Laboratory of Biology and Genetic Improvement of Maize (MOA), Beijing Key Laboratory of Crop Genetic Improvement, Joint International Research Laboratory of Crop Molecular Breeding, China Agricultural University, Beijing 100193, China. Electronic address:

Maize (Zea mays ssp. mays) was domesticated in southwestern Mexico ∼9,000 years ago from its wild ancestor, teosinte (Zea mays ssp. parviglumis) [1]. From its center of origin, maize experienced a rapid range expansion and spread over 90° of latitude in the Americas [2-4], which required a novel flowering-time adaptation. ZEA CENTRORADIALIS 8 (ZCN8) is the maize florigen gene and has a central role in mediating flowering [5, 6]. Here, we show that ZCN8 underlies a major quantitative trait locus (QTL) (qDTA8) for flowering time that was consistently detected in multiple maize-teosinte experimental populations. Through association analysis in a large diverse panel of maize inbred lines, we identified a SNP (SNP-1245) in the ZCN8 promoter that showed the strongest association with flowering time. SNP-1245 co-segregated with qDTA8 in maize-teosinte mapping populations. We demonstrate that SNP-1245 is associated with differential binding by the flowering activator ZmMADS1. SNP-1245 was a target of selection during early domestication, which drove the pre-existing early flowering allele to near fixation in maize. Interestingly, we detected an independent association block upstream of SNP-1245, wherein the early flowering allele that most likely originated from Zea mays ssp. mexicana introgressed into the early flowering haplotype of SNP-1245 and contributed to maize adaptation to northern high latitudes. Our study demonstrates how independent cis-regulatory variants at a gene can be selected at different evolutionary times for local adaptation, highlighting how complex cis-regulatory control mechanisms evolve. Finally, we propose a polygenic map for the pre-Columbian spread of maize throughout the Americas.
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http://dx.doi.org/10.1016/j.cub.2018.07.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537595PMC
September 2018

FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast Cancer by Regulating Akt/GSK3β/Β-Catenin Signaling.

Cell Physiol Biochem 2018 7;49(3):1019-1032. Epub 2018 Sep 7.

School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

Background/aims: Fibroblast growth factors (FGFs) and their high-affinity receptors contribute to autocrine and paracrine growth stimulation in several human malignant tumors, including breast cancer. However, the mechanisms underlying the carcinogenic actions of FGF18 remain unclear.

Methods: The transcription level of FGF18 under the hypoxic condition was detected with quantitative PCR (qPCR). A wound-healing assay was performed to assess the role of FGF18 in cell migration. A clonogenicity assay was used to determine whether FGF18 silencing affected cell clonogenicity. Western blotting was performed to investigate Akt/GSK3β/β-catenin pathway protein expression. Binding of β-catenin to the target gene promoter was determined by chromatin immunoprecipitation (ChIP) assays.

Results: FGF18 promoted the epithelial-mesenchymal transition (EMT) and migration in breast cancer cells through activation of the Akt/GSK3β/β-catenin pathway. FGF18 increased Akt-Ser473 and -Thr308 phosphorylation, as well as that of GSK3β-Ser9. FGF18 also enhanced the transcription of proliferation-related genes (CDK2, CCND2, Ki67), metastasis-related genes (TGF-β, MMP-2, MMP-9), and EMT markers (Snail-1, Snail-2, N-cadherin, vimentin, TIMP1). β-catenin bound to the target gene promoter on the ChIP assay.

Conclusion: FGF18 contributes to the migration and EMT of breast cancer cells following activation of the Akt/GSK3β/β-catenin pathway. FGF18 expression may be a potential prognostic therapeutic marker for breast cancer.
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http://dx.doi.org/10.1159/000493286DOI Listing
October 2018
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