Publications by authors named "Wenming Zhao"

84 Publications

Declined miR-181a-5p expression is associated with impaired natural killer cell development and function with aging.

Aging Cell 2021 Mar 29:e13353. Epub 2021 Mar 29.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

MicroRNAs (miRNAs) regulate gene expression and thereby influence cell development and function. Numerous studies have shown the significant roles of miRNAs in regulating immune cells including natural killer (NK) cells. However, little is known about the role of miRNAs in NK cells with aging. We previously demonstrated that the aged C57BL/6 mice have significantly decreased proportion of mature (CD27 CD11b ) NK cells compared with young mice, indicating impaired maturation of NK cells with aging. Here, we performed deep sequencing of CD27 NK cells from young and aged mice. Profiling of the miRNome (global miRNA expression levels) revealed that 49 miRNAs displayed a twofold or greater difference in expression between young and aged NK cells. Among these, 30 miRNAs were upregulated and 19 miRNAs were downregulated in the aged NK cells. We found that the expression level of miR-l8la-5p was increased with the maturation of NK cells, and significantly decreased in NK cells from the aged mice. Knockdown of miR-181a-5p inhibited NK cell development in vitro and in vivo. Furthermore, miR-181a-5p is highly conserved in mice and human. MiR-181a-5p promoted the production of IFN-γ and cytotoxicity in stimulated NK cells from both mice and human. Importantly, miR-181a-5p level markedly decreased in NK cells from PBMC of elderly people. Thus, our results demonstrated that the miRNAs profiles in NK cells change with aging, the decreased level of miR-181a-5p contributes to the defective NK cell development and function with aging. This opens new strategies to preserve or restore NK cell function in the elderly.
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http://dx.doi.org/10.1111/acel.13353DOI Listing
March 2021

Large-scale functional network connectivity mediate the associations of gut microbiota with sleep quality and executive functions.

Hum Brain Mapp 2021 Mar 19. Epub 2021 Mar 19.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large-scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large-scale inter- and intranetwork functional connectivity was measured using a combination of resting-state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota-brain-behavior relationships from the perspective of large-scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota.
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http://dx.doi.org/10.1002/hbm.25419DOI Listing
March 2021

The Global Landscape of SARS-CoV-2 Genomes, Variants, and Haplotypes in 2019nCoVR.

Genomics Proteomics Bioinformatics 2020 Dec 3. Epub 2020 Dec 3.

China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, haplotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.
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http://dx.doi.org/10.1016/j.gpb.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836967PMC
December 2020

African lungfish genome sheds light on the vertebrate water-to-land transition.

Cell 2021 Mar 4;184(5):1362-1376.e18. Epub 2021 Feb 4.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China. Electronic address:

Lungfishes are the closest extant relatives of tetrapods and preserve ancestral traits linked with the water-to-land transition. However, their huge genome sizes have hindered understanding of this key transition in evolution. Here, we report a 40-Gb chromosome-level assembly of the African lungfish (Protopterus annectens) genome, which is the largest genome assembly ever reported and has a contig and chromosome N50 of 1.60 Mb and 2.81 Gb, respectively. The large size of the lungfish genome is due mainly to retrotransposons. Genes with ultra-long length show similar expression levels to other genes, indicating that lungfishes have evolved high transcription efficacy to keep gene expression balanced. Together with transcriptome and experimental data, we identified potential genes and regulatory elements related to such terrestrial adaptation traits as pulmonary surfactant, anxiolytic ability, pentadactyl limbs, and pharyngeal remodeling. Our results provide insights and key resources for understanding the evolutionary pathway leading from fishes to humans.
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http://dx.doi.org/10.1016/j.cell.2021.01.047DOI Listing
March 2021

Mineral Element Deposition and Gene Expression across Different Tissues of Cherry Valley Ducks.

Animals (Basel) 2021 Jan 19;11(1). Epub 2021 Jan 19.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.

This study was conducted to investigate the deposition of several mineral elements and the mRNA levels of mineral-related genes across different tissues of cherry valley ducks. The contents of magnesium (Mg), potassium (K), zinc (Zn), and selenium (Se) in ducks' breast muscle, thigh muscle, liver, skin, and tibia at the age of 0, 21, 35, 49, and 63 days, respectively, were measured using an atomic fluorescence spectrophotometer, while the mRNA levels of mineral-related genes were detected by qRT-PCR. The results revealed that the dynamics of Mg and K were generally similar in each tissue, with a significant positive correlation ( < 0.05). In the breast muscle, thigh muscle, and liver, the contents of almost all mineral elements reached their peak values ( < 0.05) at the age of 49 to 63 days. Interestingly, the expression of most mineral-related genes was the highest at birth ( < 0.05). In addition, there was a significant negative correlation between the expression of and the deposition of K (r = -0.957, < 0.05), and a similar result was found for the expression of and the deposition of Zn (r = -0.905, < 0.05). Taken together, Mg and K could be used as joint indicators for the precise breeding of the high-quality strain of cherry valley ducks, while the age of 49 to 63 days could be used as the reference for the best marketing age. In addition, and could be used as the key genes to detect K and Zn, respectively. Hence, the findings of this study can be used to improve the production and breeding efficiency of high-quality meat ducks.
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http://dx.doi.org/10.3390/ani11010238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832843PMC
January 2021

Characterization of ovarian morphology and reproductive hormones in Zhedong white geese (Anser cygnoides domesticus) during the reproductive cycle.

J Anim Physiol Anim Nutr (Berl) 2020 Dec 30. Epub 2020 Dec 30.

College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Zhedong white goose (Anser cygnoides domesticus) is a native Chinese breed with strong broodiness and low egg production, which is related to the physiology of reproduction. However, thus far, the physiology of goose reproduction has not been well elucidated. In the present study, the ovarian morphology and reproductive hormones of Zhedong white geese were investigated during the reproductive cycle (the laying and brooding periods). The results showed that the surface of the ovary was atrophied and follicular atresia appeared to some extent in the brooding period compared with the laying period. The concentrations of follicle-stimulating hormone, progesterone and luteinizing hormone were significantly higher than those in the brooding period (p < 0.05). In contrast, the concentrations of prolactin (PRL) and anti-Müllerian hormone (AMH) in the laying period were significantly lower than those in the brooding period (p < 0.05). In addition, the mRNA expression levels of PRL, AMH, dopamine-β-hydroxylase (DβH) and cytochrome P450 side-chain cleavage enzyme (P450scc) were detected in the hypothalamus, pituitary and ovaries by using real-time polymerase chain reaction. The results showed that AMH mRNA was expressed specifically in ovary tissue. The expression levels of DβH and PRL in the brooding period was significantly higher than those in the laying period in the three tissues, especially in the early and middle stages of the brooding period. Moreover, AMH mRNA expression in the ovaries presented the same trend. In addition, P450scc mRNA was highly expressed in both the ovary and pituitary in the laying period. These results revealed the remarkable features of ovarian morphology and characterized the hormonal pattern and expression profile during the reproductive cycle, all of which contribute to understanding the differences in reproductive physiology between the laying and brooding periods in Zhedong white geese.
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http://dx.doi.org/10.1111/jpn.13494DOI Listing
December 2020

Genome Variation Map: a worldwide collection of genome variations across multiple species.

Nucleic Acids Res 2021 01;49(D1):D1186-D1191

China National Center for Bioinformation, Beijing 100101, China.

The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. It aims to collect and integrate genome variations for a wide range of species, accepts submissions of different variation types from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Compared with the previous version, particularly, a total of 22 species, 115 projects, 55 935 samples, 463 429 609 variants, 66 220 associations and 56 submissions (as of 7 September 2020) were newly added in the current version of GVM. In the current release, GVM houses a total of ∼960 million variants from 41 species, including 13 animals, 25 plants and 3 viruses. Moreover, it incorporates 64 819 individual genotypes and 260 393 manually curated high-quality genotype-to-phenotype associations. Since its inception, GVM has archived genomic variation data of 43 754 samples submitted by worldwide users and served >1 million data download requests. Collectively, as a core resource in the National Genomics Data Center, GVM provides valuable genome variations for a diversity of species and thus plays an important role in both functional genomics studies and molecular breeding.
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http://dx.doi.org/10.1093/nar/gkaa1005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778933PMC
January 2021

Mouse APOBEC3 Restriction of Retroviruses.

Viruses 2020 10 27;12(11). Epub 2020 Oct 27.

Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, 835 S. Wolcott Avenue, Chicago, IL 60612, USA.

Apolipoprotein B mRNA editing enzyme, catalytic peptide 3 (APOBEC3) proteins are critical host proteins that counteract and prevent the replication of retroviruses. Unlike the genome of humans and other species, the mouse genome encodes a single gene, which has undergone positive selection, as reflected by the allelic variants found in different inbred mouse strains. This positive selection was likely due to infection by various mouse retroviruses, which have persisted in their hosts for millions of years. While mouse retroviruses are inhibited by APOBEC3, they nonetheless still remain infectious, likely due to the actions of different viral proteins that counteract this host factor. The study of viruses in their natural hosts provides important insight into their co-evolution.
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http://dx.doi.org/10.3390/v12111217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692085PMC
October 2020

Neural correlates of the association between depression and high density lipoprotein cholesterol change.

J Psychiatr Res 2020 11 29;130:9-18. Epub 2020 Jul 29.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. Electronic address:

There is evidence that major depressive disorder (MDD) is related to serum lipid level alterations. However, the neural correlates underlying this association remain poorly understood. Forty-nine patients with MDD and fifty healthy controls (HCs) underwent structural, resting-state functional and diffusion magnetic resonance imaging scans. Voxel-based morphometry, functional connectivity (FC) and tract-based spatial statistics analyses were performed to assess brain structure and function, respectively. Blood samples were collected to measure serum levels of lipid variables including total cholesterol, triglyceride and high density lipoprotein cholesterol (HDL-C). Correlation and mediation analyses were conducted to investigate the associations of serum lipid levels with brain imaging measures in MDD patients and HCs, respectively. We found that the serum HDL-C level in MDD patients was lower than that in HCs. The lower serum HDL-C level was associated with lower gray matter volume (GMV) in ventromedial prefrontal cortex (VMPFC), higher within-network FC of the default mode network, and lower micro-structural integrity in multiple white matter regions in MDD patients. Moreover, the within-default mode network FC mediated the relationship between GMV in VMPFC and serum HDL-C level; white matter integrity in genu of corpus callosum mediated the relationship between serum HDL-C level and depressive symptom severity. However, we did not observe any correlations between serum lipids and brain imaging parameters in HCs. These findings help to identify neural correlates underlying the association between depression and serum HDL-C change, which may provide new insight into intervention, treatment and prevention of depression from the perspective of regulating serum lipids.
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http://dx.doi.org/10.1016/j.jpsychires.2020.07.012DOI Listing
November 2020

Cerebellar-cerebral dynamic functional connectivity alterations in major depressive disorder.

J Affect Disord 2020 10 15;275:319-328. Epub 2020 Jul 15.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei 230022, China. Electronic address:

Background: The cerebellum plays an important role in the neural mechanism of depression and its static functional connectivity (FC) with the cerebrum is disrupted in patients with major depressive disorder (MDD). However, cerebellar-cerebral dynamic FC alterations in MDD remain largely unknown.

Methods: 50 patients with MDD and 36 well-matched healthy controls underwent resting-state functional magnetic resonance imaging. Cerebellar-cerebral dynamic FC analyses were performed using the cerebellar seeds previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. Inter-group differences in the cerebellar dynamic FC and their associations with clinical and cognitive variables were examined.

Results: Compared to healthy controls, patients with MDD had decreased cerebellar-cerebral dynamic FC of the cerebellar subregions connecting with the executive, default-mode and affective-limbic networks. The dynamic FC of the cerebellar subregion connecting with the affective-limbic network was related to severity of depression and anxiety symptoms in MDD patients. The dynamic FC of the cerebellar subregions connecting with the default-mode and affective-limbic networks were related to sustained attention and prospective memory in controls, while the correlations were inverse or non-significant in patients.

Limitations: The fairly modest sample size and potential medication effect may increase the instability of the results.

Conclusions: Our findings provide further evidence for the pivotal role of the cerebellum in the neuropathology of depression, pointing to potential targets of cerebellar-cerebral pathways for alternative intervention or monitoring therapeutic responses.
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http://dx.doi.org/10.1016/j.jad.2020.06.062DOI Listing
October 2020

Population Genetics of SARS-CoV-2: Disentangling Effects of Sampling Bias and Infection Clusters.

Genomics Proteomics Bioinformatics 2020 Jul 12. Epub 2020 Jul 12.

Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China. Electronic address:

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estimations and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10 per site per year with a 95% confidence interval (CI) of [8.61 × 10, 8.77 × 10], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95% CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism of SARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.
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http://dx.doi.org/10.1016/j.gpb.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354277PMC
July 2020

Murine Leukemia Virus P50 Protein Counteracts APOBEC3 by Blocking Its Packaging.

J Virol 2020 08 31;94(18). Epub 2020 Aug 31.

Department of Microbiology and Immunology, University of Illinois Chicago College of Medicine, Chicago, Illinois, USA

Apolipoprotein B editing enzyme, catalytic polypeptide 3 (APOBEC3) family members are cytidine deaminases that play important roles in intrinsic responses to retrovirus infection. Complex retroviruses like human immunodeficiency virus type 1 (HIV-1) encode the viral infectivity factor (Vif) protein to counteract APOBEC3 proteins. Vif induces degradation of APOBEC3G and other APOBEC3 proteins and thereby prevents their packaging into virions. It is not known if murine leukemia virus (MLV) encodes a Vif-like protein. Here, we show that the MLV P50 protein, produced from an alternatively spliced RNA, interacts with the C terminus of mouse APOBEC3 and prevents its packaging without causing its degradation. By infecting APOBEC3 knockout (KO) and wild-type (WT) mice with Friend or Moloney MLV P50-deficient viruses, we found that APOBEC3 restricts the mutant viruses more than WT viruses Replication of P50-mutant viruses in an APOBEC3-expressing stable cell line was also much slower than that of WT viruses, and overexpressing P50 in this cell line enhanced mutant virus replication. Thus, MLV encodes a protein, P50, that overcomes APOBEC3 restriction by preventing its packaging into virions. MLV has existed in mice for at least a million years, in spite of the existence of host restriction factors that block infection. Although MLV is considered a simple retrovirus compared to lentiviruses, it does encode proteins generated from alternatively spliced RNAs. Here, we show that P50, generated from an alternatively spliced RNA encoded in , counteracts APOBEC3 by blocking its packaging. MLV also encodes a protein, glycoGag, that increases capsid stability and limits APOBEC3 access to the reverse transcription complex (RTC). Thus, MLV has evolved multiple means of preventing APOBEC3 from blocking infection, explaining its survival as an infectious pathogen in mice.
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http://dx.doi.org/10.1128/JVI.00032-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459557PMC
August 2020

Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation.

J Sex Med 2020 08 2;17(8):1457-1466. Epub 2020 Jul 2.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address:

Background: Lifelong premature ejaculation (LPE) has been linked to altered brain function and structure. Although the middle temporal gyrus (MTG) is consistently more affected in LPE, its functional and structural changes have yet to be determined at the subregional level.

Aim: To explore the functional and structural changes of MTG in LPE at the subregional level based on a combined analysis of multimodal magnetic resonance imaging data.

Methods: 25 patients with LPE and 21 healthy controls underwent resting-state functional and structural magnetic resonance imaging scans. The MTG was parcellated into the anterior part of the MTG (aMTG), middle part of the MTG, posterior part of the MTG, and sulcus part of the MTG. Resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each MTG subregion were calculated and compared between the 2 groups.

Outcomes: The functional and structural changes of MTG at the subregional level were assessed in patients with LPE and controls, as well as the correlation of them with premature ejaculation diagnostic tool and Beck Depression Inventory.

Results: Despite similar rsFC patterns of each MTG subregion in both groups, quantitative comparison analyses revealed that patients with LPE showed increased rsFC between the left aMTG and the right cuneus (0.34 ± 0.12 vs 0.17 ± 0.17), between the right aMTG and the right parahippocampal gyrus (0.36 ± 0.16 vs 0.15 ± 0.10), and between the right middle MTG and the left MTG (0.40 ± 0.14 vs 0.18 ± 0.15) relative to controls (P < .05, cluster-level family-wise error corrected). Moreover, validation analyses revealed that these results remained significant after adjusting for depression. However, there were no significant group differences in GMV in all the MTG subregions (P > .05, Bonferroni corrected). In addition, no significant correlations between rsFC and GMV of the MTG subregions and the clinical variables were found in patients with LPE (P > .05, Bonferroni corrected).

Clinical Implications: Functional hyperconnectivity in the MTG subregions may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE.

Strengths And Limitations: There are no previous studies examining functional and structural changes in LPE at the MTG subregional level. The main limitation is the small sample size.

Conclusions: We present evidence that individuals with LPE have a selective functional hyperconnectivity yet preserved structural integrity in the MTG subregions, which may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE by highlighting the critical role of the MTG in this disorder. Zhang T, Tang D, Cai H, et al. Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation. J Sex Med 2020;17:1457-1466.
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http://dx.doi.org/10.1016/j.jsxm.2020.05.006DOI Listing
August 2020

The Elements of Data Sharing.

Genomics Proteomics Bioinformatics 2020 02 28;18(1):1-4. Epub 2020 Apr 28.

China National Center for Bioinformation, Beijing 100101, China; National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.

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http://dx.doi.org/10.1016/j.gpb.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187841PMC
February 2020

Brain Structural and Functional Alterations Specific to Low Sleep Efficiency in Major Depressive Disorder.

Front Neurosci 2020 31;14:50. Epub 2020 Jan 31.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Sleep disturbance is common in patients with major depressive disorder (MDD), but the exploration of its neural underpinnings is limited by subjective sleep measurement and single-modality neuroimaging analyses.

Methods: Ninety six patients with MDD underwent polysomnography examinations and multi-modal magnetic resonance imaging (MRI) scans. According to sleep efficiency, patients were subdivided into well-matched normal sleep efficiency (NSE, = 42; 14 men; aged 43 ± 10 years) and low sleep efficiency (LSE, = 54; 23 men; aged 45 ± 12 years) groups. Inter-group differences in brain structure and function were examined by applying voxel-based morphometry (VBM), regional homogeneity (ReHo) and functional connectivity strength (FCS), and tract-based spatial statistics (TBSS) approaches to structural, functional, and diffusion MRI data, respectively.

Results: There was no significant difference in gray matter volume (GMV) between the NSE and LSE groups. Compared with the NSE group, the LSE group showed increased axial diffusivity in the left superior and posterior corona radiata, and left posterior limb and retrolenticular part of internal capsule. In addition, the LSE group exhibited decreased ReHo in the bilateral lingual gyri and right postcentral gyrus yet increased FCS in the left angular gyrus relative to the NSE group. Moreover, validation analyses revealed that these results remained after adjusting for the medication effect.

Conclusion: Our data indicate that preserved gray matter morphology, impaired white matter integrity, and decreased local synchronization degree yet increased FCS are specific to low SE in MDD patients. These findings of disassociation between structural and functional alterations might provide insights into the neural mechanisms of sleep disturbance in depression.
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http://dx.doi.org/10.3389/fnins.2020.00050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005201PMC
January 2020

The relationship between sleep efficiency and clinical symptoms is mediated by brain function in major depressive disorder.

J Affect Disord 2020 04 28;266:327-337. Epub 2020 Jan 28.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei 230022, China. Electronic address:

Background: Sleep disturbance is a common and key symptom that affects most of patients with major depressive disorder (MDD). However, neural substrates underlying sleep disturbance and their clinical relevance in depression remain unclear.

Methods: Ninety-six MDD patients underwent resting-state functional MRI. Fractional amplitude of low-frequency fluctuation (fALFF) and resting-state functional connectivity (rsFC) were used to measure brain function. Overnight polysomnography was performed to objectively measure sleep efficiency (SE), which was used to classify patients into normal sleep efficiency (NSE) and low sleep efficiency (LSE) groups. Between-group differences in fALFF and rsFC were examined using two-sample t-tests. Moreover, correlation and mediation analyses were conducted to test for potential associations between SE, brain functional changes, and clinical variables.

Results: LSE group showed decreased fALFF in right cuneus, thalamus, and middle temporal gyrus compared to NSE group. MDD patients with low SE also exhibited lower rsFC of right cuneus to right lateral temporal cortex, which was associated with more severe depression and anxiety symptoms. More importantly, mediation analyses revealed that the relationships between SE and severity of depression and anxiety symptoms were significantly mediated by the altered rsFC. In addition, these low SE-related brain functional alterations were not affected by antidepressant medication and were independent of structural changes.

Limitations: The lack of healthy controls because of "first-night effect".

Conclusion: These findings not only may expand existing knowledge about neuropathology of sleep disturbance in depression, but also may inform real-world clinical practice by improving depression and anxiety symptoms through sleep regulation.
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http://dx.doi.org/10.1016/j.jad.2020.01.155DOI Listing
April 2020

Identification of QTLs for resistance to maize rough dwarf disease using two connected RIL populations in maize.

PLoS One 2019 17;14(12):e0226700. Epub 2019 Dec 17.

Plant Protection Institute, Henan Academy of Agricultural Sciences, Zhengzhou, China.

Maize rough dwarf disease (MRDD) is a significant viral disease caused by rice black-streaked dwarf virus (RBSDV) in China, which results in 30% yield losses in affected summer maize-growing areas. In this study, two connected recombinant inbred line (RIL) populations were constructed to elucidate the genetic basis of resistance during two crop seasons. Ten quantitative trait loci (QTLs) for resistance to MRDD were detected in the two RILs. Individual QTLs accounted for 4.97-23.37% of the phenotypic variance explained (PVE). The resistance QTL (qZD-MRDD8-1) with the largest effect was located in chromosome bin 8.03, representing 16.27-23.37% of the PVE across two environments. Interestingly, one pair of common significant QTLs was located in the similar region on chromosome 4 in both populations, accounting for 7.11-9.01% of the PVE in Zheng58×D863F (RIL-ZD) and 9.43-13.06% in Zheng58×ZS301 (RIL-ZZ). A total of five QTLs for MRDD resistance trait showed significant QTL-by-Environment interactions (QEI). Two candidate genes associated with resistance (GDSL-lipase and RPP13-like gene) which were higher expressed in resistant inbred line D863F than in susceptible inbred line Zheng58, were located in the physical intervals of the major QTLs on chromosomes 4 and 8, respectively. The identified QTLs will be studied further for application in marker-assisted breeding in maize genetic improvement of MRDD resistance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917286PMC
April 2020

Selective microstructural integrity impairments of the anterior corpus callosum are associated with cognitive deficits in obstructive sleep apnea.

Brain Behav 2019 12 20;9(12):e01482. Epub 2019 Nov 20.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: There is some evidence that obstructive sleep apnea (OSA) patients have white matter integrity abnormality in the corpus callosum (CC). However, whether the CC subregions are differentially affected in OSA is largely unknown.

Methods: Twenty patients with OSA and 24 well-matched healthy controls were enrolled and underwent diffusion tensor imaging (DTI) and clinical and cognitive assessments. DTI tractography was used to reconstruct the CC which was divided into five subregions. Intergroup differences in multiple diffusion metrics of each CC subregion and their correlations with clinical and cognitive parameters were tested.

Results: In comparison with healthy controls, OSA patients exhibited white matter integrity alterations in the anterior CC, characterized by increased radial diffusivity (RD) in the subregion 1 and decreased fractional anisotropy (FA) along with increased mean diffusivity (MD) and RD in the subregion 2. Moreover, we found that the lower microstructural integrity in the anterior CC was correlated with worse prospective memory and sustained attention in OSA patients.

Conclusions: These findings indicate that the selective impairments of the anterior CC may help clarify the neural correlates of cognitive impairments in OSA.
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http://dx.doi.org/10.1002/brb3.1482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908858PMC
December 2019

MiR-942 regulates the function of breast cancer cell by targeting FOXA2.

Biosci Rep 2019 11;39(11)

Department of Pathology, Baoding No.1 Central Hospital, Baoding City, Hebei Province, China.

MicroRNA (MiR)-942 regulates the development of a variety of tumors, however, its function in breast cancer (BCa) has been less reported. Therefore, the present study investigated the regulatory effects of miR-942 on BCa cells. The expression of miR-942 in whole blood samples and BCa cell lines was detected by quantitative real-time (qRT)-PCR. Direct target gene for miR-942 was confirmed by dual-luciferase reporter assay. FOXA2 expression in adjacent tissues was detected by qRT-PCR. The effects of miR-942, or miR-942 with FOXA2, on the cell viability, proliferation, apoptosis, migration and invasion of BCa cells were determined by cell counting kit-8 (CCK-8), colony formation assay, flow cytometry, wound scratch and Transwell, respectively. The levels of N-Cadherin, E-Cadherin and Snail were determined by Western blot. Kaplan-Meier was used to explore the relationship among the expressions of miR-942 and FOXA2 and the prognosis of BCa patients. MiR-942 had high expressed in BCa, while its low expression significantly suppressed the cell viability, proliferation, migration and invasion of BCa, but increased cell apoptosis. Down-regulation of N-Cadherin and Snail and up-regulation of E-Cadherin were also induced by low-expression of miR-942. FOXA2, which was proved as the direct target gene for miR-942 and was low-expressed in BCa, partially reversed the effect of overexpressed miR-942 on promoting cell viability, proliferation, migration and invasion, and suppressed cell apoptosis. A lower survival rate was observed in BCa patients with a high expression of miR-942 and a low expression of FOXA2. MiR-942 promoted the progression of BCa by down-regulating the expression of FOXA2.
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http://dx.doi.org/10.1042/BSR20192298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879377PMC
November 2019

Comparative characterization of bacterial communities in geese consuming of different proportions of ryegrass.

PLoS One 2019 25;14(10):e0223445. Epub 2019 Oct 25.

Laboratory of Animal Genetics and Rearing and Molecular Design of Jiangsu Province, Yangzhou University, Yangzhou, PR, China.

Geese are extremely well-adapted to utilizing plant-derived roughage in their diet, so the grass must be added to commercial diets under intensive rearing systems. However, it is unclear whether the gut microbiota will change significantly when adding different proportions of ryegrass. In this study, 240 healthy male Yangzhou geese (28 days old) with similar body weights were randomly divided into four groups and fed different proportions grass (CK, whole commercial diets; EG1, ryegrass: commercial diets = 1.5:1; EG2, ryegrass: commercial diets = 2:1; EG3, ryegrass: commercial diets = 3:1) respectively. When the geese grew to 70 days old, their intestines were collected and high-throughput sequencing technology was performed to investigate the microbial diversity in the caecum of geese with different dietary supplements. There was no obvious change in the alpha diversity of gut microbiota of geese with ryegrass intake (P > 0.05) and the composition of dominant bacterium (including Bacteroidetes and Firmicutes) was also similar. However, the ratio between Firmicutes and Bacteroidetes was remarkably reduced with ryegrass intake (P < 0.05), and the relative abundance of 30 operational taxonomic units (OTUs) significantly differed. Additionally, the content of cellulose-degrading microbiota such as Ruminiclostridium and Ruminococcaceae UCG-010 were significantly increased in geese fed with increasing amounts of grass. Finally, the functional profiles of the goose gut microbiota were explored using the PICRUSt tool. Carbohydrate metabolism and amino acid metabolism were dominant metabolic pathways. Lipid metabolism was significantly increased in EG3 compared that in the CK group (P < 0.05). Interestingly, Turicibacter and Parasutterella may have affected abdominal fat deposition as grass intake increased. Taken together, although the diversity of bacterial communities was similar in geese fed with different proportions of ryegrass, cellulose-degrading microbiota (Ruminiclostridium and Ruminococcaceae UCG-010) were abundant and the lipid metabolic pathway was enriched, which may reduce abdominal fat accumulation in high-ryegrass fed geese.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223445PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814310PMC
March 2020

The Relationship Between Serum Concentration of Vitamin D, Total Intracranial Volume, and Severity of Depressive Symptoms in Patients With Major Depressive Disorder.

Front Psychiatry 2019 9;10:322. Epub 2019 May 9.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Depression has been linked to vitamin D deficiency. However, little attention was paid to the neural substrate underlying this association. Fifty patients with major depressive disorder (MDD) were enrolled in this study. High-resolution structural magnetic resonance imaging was performed to calculate total intracranial volume (TIV). Peripheral venous blood samples were collected to measure serum vitamin D concentration. Hamilton Rating Scale for Depression (HAMD) was used to assess severity of depression symptoms. The relationship among TIV, serum vitamin D concentration, and HAMD score was examined using correlation, linear regression, and mediation analyses. In patients with MDD, HAMD score was negatively correlated with TIV and serum vitamin D concentration, and TIV was positively correlated with serum vitamin D concentration. Linear regression analyses showed that TIV and serum vitamin D concentration were significant predictors of HAMD score. Importantly, mediation analysis revealed that TIV significantly mediated the relationship between serum vitamin D concentration and HAMD score. Our findings suggest that TIV may serve as a potential neural biomarker for monitoring responses to adjuvant therapy of vitamin D in patients with MDD.
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http://dx.doi.org/10.3389/fpsyt.2019.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520644PMC
May 2019

Pineal gland abnormality in major depressive disorder.

Psychiatry Res Neuroimaging 2019 07 15;289:13-17. Epub 2019 May 15.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address:

Patients with major depressive disorder (MDD) often have circadian rhythm alteration and sleep disturbance. The pineal gland regulates the circadian rhythm and sleep by the secretion of melatonin neurohormone. However, the relationship between pineal abnormality and MDD remains elusive. 50 patients with MDD and 35 gender- and age-matched healthy controls underwent high-resolution structural MRI. Pineal parenchymal volume (PPV) was measured manually. Inter-group differences in prevalence of pineal cyst and PPV were examined. In addition, we investigated the correlations between PPV and symptom severity as well as sleep variables in the patient group. Compared to healthy controls, patients with MDD had a higher prevalence of pineal cyst. Moreover, patients had significantly decreased PPV relative to controls. However, no significant correlations were observed between PPV and symptom severity as well as sleep variables. Our findings suggest that pineal abnormality may play a critical role in depression.
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http://dx.doi.org/10.1016/j.pscychresns.2019.05.004DOI Listing
July 2019

Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle.

Cell Microbiol 2019 08 16;21(8):e13038. Epub 2019 May 16.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Influenza virus matrix 1 protein (M1) is highly conserved and plays essential roles at many stages of virus life cycle. Here, we used a yeast two-hybrid system to identify the host protein SLD5, a component of the GINS complex, which is essential for the initiation of DNA replication in eukaryotic cells, as a new M1 interacting protein. M1 from several different influenza virus strains all interacted with SLD5. Overexpression of SLD5 suppressed influenza virus replication. Transient, stable, or inducible expression of M1 induced host cell cycle blockade at G0/G1 phase. Moreover, SLD5 partially rescued M1 expression- or influenza virus infection-induced G0/G1 phase accumulation in cell lines and primary mouse embryonic fibroblasts. Importantly, SLD5 transgenic mice exhibited higher resistance and improved lung epithelial regeneration after virus infection compared with wild-type mice. Therefore, influenza virus M1 blocks host cell cycle process by interacting with SLD5. Our finding reveals the multifunctional nature of M1 and provides new insight for understanding influenza virus-host interaction.
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http://dx.doi.org/10.1111/cmi.13038DOI Listing
August 2019

Differential impairment patterns of the corticospinal tract segments in alcohol dependence.

Int J Psychiatry Clin Pract 2019 Sep 15;23(3):225-230. Epub 2019 Apr 15.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University , Hefei , China.

Previous studies have reported inconsistent findings regarding corticospinal tract (CST) changes in alcohol dependence. Here, we aimed to clarify this issue by examining the micro-structural integrity differences of distinct CST segments between alcohol-dependent patients and healthy controls. Diffusion tensor imaging was performed in a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls. CST was reconstructed using tractography and was divided into inferior and superior segments at the level of the lateral sulcus. Multiple diffusion measures of each segment were compared between two groups. For the bilateral whole CSTs, no diffusion measures showed significant between-group differences. However, compared to healthy controls, alcohol-dependent patients exhibited decreased FA and increased RD in the left-superior segment, increased FA and decreased RD/MD in the left-inferior segment, increased AD/MD in the right-superior segment, decreased RD/MD in the right-inferior segment. These findings suggest that CST impairments may vary with the fibre arrangement patterns of its segments in alcohol dependence. Keypoints We reconstructed the CST using tractography based on DTI data and divided the CST into different segments in order to explore more detailed micro-structural integrity changes in alcoholisms. Alcohol-dependent patients showed decreased RD and MD for the bilateral inferior segments of the CSTs. The left-superior segment exhibited decreased FA and increased RD while the right one exhibited increased AD and MD. These findings suggest that CST impairments may vary with the fiber arrangement patterns of its segments in alcohol dependence. In future work, more elaborate segmentation schemes and lager samples should be used to test the reproducibility of our findings.
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http://dx.doi.org/10.1080/13651501.2019.1588328DOI Listing
September 2019

Abnormal coupling among spontaneous brain activity metrics and cognitive deficits in major depressive disorder.

J Affect Disord 2019 06 8;252:74-83. Epub 2019 Apr 8.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address:

Background: A variety of functional metrics derived from resting-state functional magnetic resonance imaging (rs-fMRI) have been employed to explore spontaneous brain activity changes in major depressive disorder (MDD) and have enjoyed significant success in unraveling the neurobiological mechanisms underlying this disorder. However, it is unclear whether spatial and temporal coupling relationships among these rs-fMRI metrics are altered in MDD.

Methods: 50 patients with MDD and 36 well-matched healthy controls underwent rs-fMRI scans. A dynamic analysis was applied to compute multiple frequently used metrics including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity. Kendall's W was used to calculate volume-wise (across voxels) and voxel-wise (across time windows) concordance among these metrics. Inter-group differences in the concordance and their associations with clinical and cognitive variables were tested.

Results: Compared to healthy controls, patients with MDD showed decreased whole gray matter volume-wise concordance. Despite similar spatial distributions, quantitative comparison analysis revealed that MDD patients exhibited reduced voxel-wise concordance in multiple cortical and subcortical regions. Moreover, the lower concordance was associated with worse performances in prospective memory and sustained attention in the MDD group.

Limitations: The study design of fairly modest sample size did not allow us to perform a full analysis of the potential effects of medication and illness duration.

Conclusions: Our findings suggest that spatial and temporal decoupling of multiple resting-state brain activity metrics may help elucidate the neural mechanisms of cognitive deficits in depression.
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http://dx.doi.org/10.1016/j.jad.2019.04.030DOI Listing
June 2019

iDog: an integrated resource for domestic dogs and wild canids.

Nucleic Acids Res 2019 01;47(D1):D793-D800

BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

The domestic dog (Canis lupus familiaris) is indisputably one of man's best friends. It is also a fundamental model for many heritable human diseases. Here, we present iDog (http://bigd.big.ac.cn/idog), the first integrated resource dedicated to domestic dogs and wild canids. It incorporates a variety of omics data, including genome sequences assemblies for dhole and wolf, genomic variations extracted from hundreds of dog/wolf whole genomes, phenotype/disease traits curated from dog research communities and public resources, gene expression profiles derived from published RNA-Seq data, gene ontology for functional annotation, homolog gene information for multiple organisms and disease-related literature. Additionally, iDog integrates sequence alignment tools for data analyses and a genome browser for data visualization. iDog will not only benefit the global dog research community, but also provide access to a user-friendly consolidation of dog information to a large number of dog enthusiasts.
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http://dx.doi.org/10.1093/nar/gky1041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323916PMC
January 2019

NucMap: a database of genome-wide nucleosome positioning map across species.

Nucleic Acids Res 2019 01;47(D1):D163-D169

BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

Dynamics of nucleosome positioning affects chromatin state, transcription and all other biological processes occurring on genomic DNA. While MNase-Seq has been used to depict nucleosome positioning map in eukaryote in the past years, nucleosome positioning data is increasing dramatically. To facilitate the usage of published data across studies, we developed a database named nucleosome positioning map (NucMap, http://bigd.big.ac.cn/nucmap). NucMap includes 798 experimental data from 477 samples across 15 species. With a series of functional modules, users can search profile of nucleosome positioning at the promoter region of each gene across all samples and make enrichment analysis on nucleosome positioning data in all genomic regions. Nucleosome browser was built to visualize the profiles of nucleosome positioning. Users can also visualize multiple sources of omics data with the nucleosome browser and make side-by-side comparisons. All processed data in the database are freely available. NucMap is the first comprehensive nucleosome positioning platform and it will serve as an important resource to facilitate the understanding of chromatin regulation.
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http://dx.doi.org/10.1093/nar/gky980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323900PMC
January 2019

Depleting the carboxy-terminus of human Wnt5a attenuates collagen-induced arthritis in DBA/1 mice.

Biochem Biophys Res Commun 2018 10 11;504(4):679-685. Epub 2018 Sep 11.

Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing, 100069, PR China. Electronic address:

Wnt5a signalling plays pathological roles in synovial inflammation and bone destruction. In the present study, we designed four human Wnt5a-based DNA recombinants and detected their effects on immunogenicity and anti-rheumatism in a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning showed that the phWnt5a-NL was superior to other recombinants because it resulted in decreased severity of arthritis, histopathological scores of synovial inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum concentrations of the rheumatoid-associated cytokines IL-1β and RANKL and in osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL treatment increased the percentage of Treg cells. Finally, western blotting analysis showed that the phWnt5a-NL-immunization interrupted β-catenin and JNK expression in osteoclast precursors derived from the CIA mice. The results suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may be beneficial for the treatment of chronic inflammatory disorders involving bone resorption.
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http://dx.doi.org/10.1016/j.bbrc.2018.09.030DOI Listing
October 2018

Disrupted topological organization of the motor execution network in alcohol dependence.

Psychiatry Res Neuroimaging 2018 10 10;280:1-8. Epub 2018 Aug 10.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei 230022, China. Electronic address:

Motor function damage is one of the most common symptoms in patients with alcohol dependence (AD). However, relatively little is known about the neuropathology of the motor impairments in AD. The aim of this study was to identify changes in the topological organization of the motor execution network in AD. Here, a total of 39 male individuals, including 19 AD patients and 20 age-matched healthy controls, underwent resting-state functional magnetic resonance imaging (fMRI). The motor execution network was constructed and analyzed using graph theoretical approaches. Topological properties (including global, nodal and edge measures) were compared between the two groups. At the global level, AD patients exhibited increased local specialization (indexed by increased clustering coefficient and local efficiency) relative to healthy controls, indicating that the motor execution network of AD patients shifts toward regularization. At the node level, nodal degree was higher in AD patients in the cerebellum. At the edge level, we observed a cerebello-thalamo-striato-cortical circuit with altered functional connectivity strength in AD patients. These findings suggest that topological architecture of the motor execution network is disrupted in AD patients, which may provide important insights into the neurobiology of the AD-related motor impairments.
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http://dx.doi.org/10.1016/j.pscychresns.2018.08.006DOI Listing
October 2018

Screening and bioinformatics analysis of circular RNA expression profiles in hepatitis B-related hepatocellular carcinoma.

Cancer Biomark 2018 ;22(4):631-640

Interventional Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.

Background: Circular RNAs (circRNAs) play an important role in pathogenesis and development of hepatocellular carcinoma (HCC). However, circRNA expression profiles in hepatitis B Virus (HBV)-related HCC remain to be studied.

Methods: Total 13 HBV-related HCC patients were enrolled for study. Three HCC and 3 paired adjacent non-tumorous (NT) tissues from 3 patients were performed for microarray. Ten pairs of HCC tissues were used to verify the identified up-regulated and down-regulated circRNAs obtained from the microarray data by quantitative real-time reverse transcription PCR (qRT-PCR). Total RNA was isolated and treated with Rnase R to remove linear RNA, then hybridized to the array to screen for circRNAs. Bioinformatics analyses including clustering, differential expression, annotation of circRNA/microRNA (miRNA) interactions, Go analysis and KEGG pathway analysis, were performed.

Results: Based on the microarray data, we found significantly up-regulation of 24 circRNAs and down-regulation of 23 circRNAs in the HCC samples compared to NT samples (fold change ⩾ 2.0 and P< 0.05). Of them, 6 candidate circRNAs (hsa_circRNA_102814, 100381, 103489, 101764, 100327, and 103361) were verified by qRT-PCR. Of them, hsa_circRNA 100381, 103489 up-regulation and 101764 down-regulation were found to be significantly different in the 10 validation HCC tissue. Clusters of circRNAs were aberrantly expressed in HCC compared with NT samples. CircRNA_101764 was the largest nodes in circRNA/microRNA co-expression network, especially co-expression with hsa-miR-181 family, which plays an important role in cell network. Annotation of circRNA/miRNA interactions indicated that the biological effects of circRNA may be achieved by binding of miRNAs. GO analysis revealed that numerous target genes were involved in the biological processes, cellular component and molecular function. There was nearly 30 target genes enrichment on KEGG pathways analysis, PI3K-Akt signaling pathway which the most number of genes involved.

Conclusion: In this study, we comprehensively explored the expression of differentially expressed circRNAs in HBV-related HCC, and our results indicate that circRNA_101764 may play an important role in the development of HCC.
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http://dx.doi.org/10.3233/CBM-170910DOI Listing
November 2018