Publications by authors named "Ming Shao"

133 Publications

Short-term effects of ambient temperature and pollutants on the mortality of respiratory diseases: A time-series analysis in Hefei, China.

Ecotoxicol Environ Saf 2021 Mar 24;215:112160. Epub 2021 Mar 24.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

Background: The air pollution has become an important environmental health problem due to its adverse health effect. The objective of this study was to investigate the effects of ambient temperature and pollutants on mortality of respiratory diseases (RD) in Hefei, China, a typical inland city.

Methods: Nonlinear exposure-response dependencies and delayed effects of urban daily mean temperature (DMT) and pollutants were evaluated by distributed lag non-linear models (DLNM). To further explore this effect, different genders and ages were also examined by stratified analysis.

Results: A total of 12876 deaths from RD were collected from January 1, 2014 to December 31, 2018 in Hefei, China. There was a U-shaped correlation between DMT and RD mortality, and the RD mortality rised by 11.6% (95% CI: 2.2-22.0%) when the DMT was 35.8 °C (reference temperature is 20 °C). The results show that risk of death with short-term exposure to elevated concentrations of PM and SO was not significant. The maximum hysteresis and cumulative relative risk (RR) of RD mortality were 1.012 (95% CI: 1.003 ~ 1.021, lag 0 day) and 1.072 (95% CI: 1.014 ~1.133, lag 10 days) for each 10 μg/m augment in NO; 1.005 (95% CI: 1.001-1.009, lag 0 day) and 1.027 (95% CI: 1.004-1.051, lag 10 days) for each 10 μg/m augment in O a negative association between CO exposure and the cumulative risk of death was observed (RR = 0.964, 95% CI: 0.935-0.993, lag 07 days). Subgroup analysis showed the effect of high temperatures, NO O and CO exposure was still statistically significant for the elderly and male.

Conclusion: The present study found that short-term exposure to high temperature, NO O and CO were significantly associated with the risk of RD mortality and male as well as elderly are more susceptible to these factors.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112160DOI Listing
March 2021

Survey on the Analysis and Modeling of Visual Kinship: A Decade in the Making.

IEEE Trans Pattern Anal Mach Intell 2021 Mar 2;PP. Epub 2021 Mar 2.

Kinship recognition is a challenging problem with many practical applications. With much progress and milestones having been reached after ten years - we are now able to survey the research and create new milestones. We review the public resources and data challenges that enabled and inspired many to hone-in on the views of automatic kinship recognition in the visual domain. The different tasks are described in technical terms and syntax consistent across the problem domain and the practical value of each discussed and measured. State-of-the-art methods for visual kinship recognition problems, whether to discriminate between or generate from, are examined. As part of such, we review systems proposed as part of a recent data challenge held in conjunction with the 2020 IEEE Conference on Automatic Face and Gesture Recognition. We establish a stronghold for the state of progress for the different problems in a consistent manner. This survey will serve as the central resource for the work of the next decade to build upon. For the tenth anniversary, the demo code is provided for the various kin-based tasks. Detecting relatives with visual recognition and classifying the relationship is an area with high potential for impact in research and practice.
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http://dx.doi.org/10.1109/TPAMI.2021.3063078DOI Listing
March 2021

Epigenetics of ankylosing spondylitis: Recent developments.

Int J Rheum Dis 2021 Apr 19;24(4):487-493. Epub 2021 Feb 19.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease which mainly affects the spine, sacroiliac joint and peripheral joints. To date, the exact causes and pathogenesis of AS still remain unknown. It is considered that the pathogenesis of AS is associated with genetic, infection, environment, immunity and other factors. Among them, the role of genetic factors in the pathogenesis of AS has been studied most deeply. However, over the past few years, the function of environmental predisposition and epigenetic modification in the pathogenesis of AS has received extensive attention. This paper summarizes the recent progress in the epigenetics of AS, including abnormal epigenetic modifications at AS-associated genomic loci, such as DNA methylation, histone modification, microRNA, and so on. In summary, the findings of this review attempt to explain the role of epigenetic modification in the occurrence and development of AS. Nevertheless, there are still unknown and complicated aspects worth exploring to deepen our understanding of the pathogenesis of AS.
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http://dx.doi.org/10.1111/1756-185X.14080DOI Listing
April 2021

Characteristics and controls of solute transport under different conditions of soil texture and vegetation type in the water-wind erosion crisscross region of China's Loess Plateau.

Chemosphere 2021 Jan 16;273:129651. Epub 2021 Jan 16.

Key Laboratory of Ecosystem Network Observation and Modeling, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, China; College of Natural Resources and Environment, State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Northwest A & F University, Yangling, 712100, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.

The analysis of solute transport characteristics in soil is of great significance in understanding nutrient cycling and pollutant migration in the Earth's Critical Zone. The objective of this study was to investigate the transport characteristics and the influencing factors of Cl in soils with different textures (sandy-S and loamy-L), and covered by different vegetation types (arbor-AR, shrub-SH and grass-GR) in the water-wind erosion crisscross region of the northern Loess Plateau of China. Results showed that the initial penetration time (TS: 12-80 min), entire penetration time (TE: 75-480 min), average flow velocity in the pore (V: 0.52-1.98 cm h) and the hydrodynamic diffusion coefficient (D: 0.75-2.55 cm h) of Cl varied with different soil textures and vegetation types, and at different soil depths. The V and D associated with Cl transport were highest in the 0-20 cm soil layer and decreased with increasing depth, while the opposite trend was observed for TS and TE. For the 0-1 m soil profile of the same texture but covered by different vegetation types, the average V and D followed the order of S-AR > S-GR > S-SH and L-AR > L-SH > L-GR, while the average TS and TE exhibited the exact opposite order. This behavior is caused by the varying distributions of root biomass under different vegetation types that affect the number of macropores, the connectivity density and the preferential flow paths in the soil. For the 0-1 m soil profiles of different textures covered by the same vegetation type, the average V and D followed the order of S-AR > L-AR; S-SH > L-SH; and S-GR > L-GR, while the average TS and TE showed the opposite trend. This is because the pore size and distribution in soil are significantly affected by soil mechanical composition. There are significant correlations between soil properties (e.g., bulk density, number of macropores, pore connectivity density, saturated hydraulic conductivity, soil organic carbon content and particle composition) and the transport parameters (e.g., V, TS, and TE). The pedotransfer functions using readily available soil properties can adequately predict V of Cl transport under different conditions of soil texture and vegetation type. These results provide guidance for the rational configuration of artificial vegetation in different textural soils with respect to reduce nutrient loss and improve ecosystem functions in the northern Loess Plateau of China.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129651DOI Listing
January 2021

Rbm24a Is Necessary for Hair Cell Development Through Regulating mRNA Stability in Zebrafish.

Front Cell Dev Biol 2020 17;8:604026. Epub 2020 Dec 17.

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.

Hair cells in the inner ear and lateral lines are mechanosensitive receptor cells whose development and function are tightly regulated. Several transcription factors as well as splicing factors have been identified to play important roles in hair cell development, whereas the role of RNA stability in this process is poorly understood. In the present work, we report that RNA-binding motif protein 24a (Rbm24a) is indispensable for hair cell development in zebrafish. expression is detected in the inner ear as well as lateral line neuromasts. Albeit deficient zebrafish do not survive beyond 9 days post fertilization (dpf) due to effects outside of the inner ear, deficiency does not affect the early development of inner ear except for delayed otolith formation and semicircular canal fusion. However, hair cell development is severely affected and hair bundle is disorganized in mutants. As a result, the auditory and vestibular function of mutants are compromised. RNAseq analyses identified several Rbm24a-target mRNAs that are directly bound by Rbm24a and are dysregulated in mutants. Among the identified Rbm24a-target genes, , , and are particularly interesting as their dysregulation might contribute to the inner ear phenotypes in mutants. In conclusion, our data suggest that Rbm24a affects hair cell development in zebrafish through regulating mRNA stability.
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http://dx.doi.org/10.3389/fcell.2020.604026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773828PMC
December 2020

Tumor Necrosis Factor α Reduces SNAP29 Dependent Autolysosome Formation to Increase Prion Protein Level and Promote Tumor Cell Migration.

Virol Sin 2020 Nov 25. Epub 2020 Nov 25.

Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

Tumor Necrosis Factor α (TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein (PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration; this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B (NF-κB) signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3 (FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29 (SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated, and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.
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http://dx.doi.org/10.1007/s12250-020-00320-4DOI Listing
November 2020

Down-Regulation of miR-7 in Gastric Cancer Is Associated With Elevated LDH-A Expression and Chemoresistance to Cisplatin.

Front Cell Dev Biol 2020 22;8:555937. Epub 2020 Sep 22.

Department of Bloood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

MicroRNAs (miRNAs) are dysregulated in the context of many cancer types, making them potentially ideal diagnostic or therapeutic targets in patients in which they are aberrantly expressed. In the present study, we found miR-7 to be downregulated in gastric cancer (GC), and we further determined its expression to be closely linked to GC sensitivity to the chemotherapeutic compound cisplatin. This effect appears to be at least partially attributable to the regulation of LDH-A, which is a miR-7 target gene and expression of LDH-A is negatively correlated with miR-7 expression in primary GC tumor samples. When upregulated, we also determined that miR-7 was able to inhibit the proliferation, colony formation, and glycolysis of GC cells owing to its regulation of LDH-A. Moreover, overexpression of miR-7 render cells more sensitive to cisplatin. Our results thus provide novel evidence that miR-7 is a key mediator of GC growth and chemosensitivity through its regulation of LDH-A, thus potentially highlighting this pathway as a therapeutic target for treating affected patients.
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http://dx.doi.org/10.3389/fcell.2020.555937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536350PMC
September 2020

[Genotyping for Auxiliary Identification of Anti-C Alloantibody with Anti-f Autoantibody Mimicking Alloantibody].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Oct;28(5):1740-1745

Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China,E-mail:

Objective: To identify the difficult antibody specificity of 1 PNH patient with blood transfusion history by genotyping.

Methods: RH typing of this patient was performed using gel card method, the antibody specificity was identified by panel cells, the RH-unrelated phenotype were excluded by genotyping method in difficult condition of serologic identification, furthmore different RH phenotype cells were used for adsorption-elution so as to re-examine the reactivity of antibodies in this patient's serum, and finally different RH phenotype cells were combined to exclude other unrelated antibodies.

Results: The RH phenotype presented as double population for C antigen, and positive agglutination for the other antigens. The results of RHD zygote, together with RHD and RHCE sequencing showed that the RHD genotype was homozygous RHD/RHD, and the c.122A>G mutation did not found in RHCE gene, thus C antigen was excluded; 48G lies in the 1st exon, the 5th exon showed nt676 G/C heterozygosity, the 2nd-4th, 6th-10th exons did not show mutations, however a new mutation was found in the 4th intron IVS4+29A>C. It can be judged that the RH genotype was Dce/DcE, and its phenotype should be ccDEe. The anti-C alloantibody and rare anti-f autoantibody mimicking alloantibody in serum was determined by different RH phenotypic cell absorption-elution. Finally, cross-matched AB ccDEE blood units were selected for the patient and there was no adverse reactions of blood transfusion occurred.

Conclusion: Genotyping can be auxiliarily applied to the identification of difficult antibodies in serum of a patient, thereby reducing the risk of blood transfusion.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.05.051DOI Listing
October 2020

Characteristics of HIV-1 env genes from Chinese chronically infected donors with highly broad cross-neutralizing activity.

Virology 2020 12 28;551:16-25. Epub 2020 Sep 28.

State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. Electronic address:

Knowledge about the special characteristics of HIV-1 envelope (env) glycoproteins in rare individuals developing >90% neutralization breadth in Chinese subtype B' slow progressors may provide insights for vaccine design against local viruses. We performed a cross-sectional analysis on 7 samples. We tested the neutralization breadth and geometric mean ID50 titers (GMTs) of these samples, and divided them into hBCN+ and hBCN- group according to whether their neutralization breadth >90%. We obtained env sequences in these samples through single genome amplification (SGA) assay. By comparing with hBCN-, subtype B chronically infected group (B-SP), and Chinese subtype B group (B-Database), we analyzed the characteristics of the env sequences of hBCN+ group. Longer V1 and V4 regions with more glycosylation sites were found in hBCN+ samples compared to hBCN- samples. Further analysis compared to B-SP and B-Database showed that hBCN+ group exhibited unique extra-long V1 region containing higher proportion of N-glycan sites and additional cysteines.
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http://dx.doi.org/10.1016/j.virol.2020.08.012DOI Listing
December 2020

VitSeg: Weakly supervised vitiligo segmentation in skin image.

Comput Med Imaging Graph 2020 Oct 26;85:101779. Epub 2020 Aug 26.

Dept. of Computer and Information Science, University of Massachusetts Dartmouth, Dartmouth, MA, USA. Electronic address:

Vitiligo is a typical pigmented skin disorder, which affects up to 1% of the global population, and the appearance of the patient is severely affected. Its lesions are often characterized by large affected areas, irregular shapes, low contrast, and the difficulty of identifying under natural light. This paper proposes a weakly supervised vitiligo segmentation framework using only image-level annotation to perform segmentation. We first roughly locate the lesion region through the class activation map - the byproduct of a CNN-based classification model. By further exploring the class activation map and leveraging the local information of the image, we perform saliency propagation to produce segmentation with accurate boundaries and strong interpretability. Moreover, we collect a vitiligo image dataset named Vit2019, which contains 2000 images; to our best knowledge, this is so far the largest image dataset for vitiligo. The experiment shows our method not only achieves good results on Vit2019 with IoU of 72.7%, but also on the ISIC-2017 dataset, which contains other types of pigmented skin diseases (e.g., nevus, melanoma and seborrheic keratoses), our method achieves IoU of 54.2%. Our experiments demonstrate the superiority of the proposed model over the state-of-the-art.
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http://dx.doi.org/10.1016/j.compmedimag.2020.101779DOI Listing
October 2020

Superoxide-induced Type I collagen secretion depends on prolyl 4-hydroxylases.

Biochem Biophys Res Commun 2020 09 30;529(4):1011-1017. Epub 2020 Jul 30.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, 78 Heng Zhi Gang Road, Guangzhou, 510095, China. Electronic address:

Reactive oxygen species (ROS) including superoxide (O) play an important role in a variety of diseases, including Alzheimer's Disease, cancer, and atherosclerosis. Early reports showed that O is a stimulant for collagen synthesis. However, the mechanism remains incompletely understood. Here we showed that LY83583 (6-anilinoquinoline-5,8-quinone), a substance known to induce O production by smooth muscle cell (SMC), increases Type I collagen secretion. This effect could be blocked by treating the cells with Tiron, a scavenger for O. LY83583-induced Type I collagen secretion required P4HA1 and P4HA2. Knockout of either P4ha1 or P4ha2 greatly reduced LY83583-stimulated Type I collagen maturation whereas silencing of both P4ha1 and P4ha2 completely blocked LY83583-induced Type I collagen maturation. Although significantly more hydroxyproline on purified Type I collagen was detected from LY83583 treated mouse embryonic fibroblast (MEF) cells by mass spectrometry, the level of prolyl 4-hydroxylases was not altered. Thus, LY83583 might increase the enzymatic activity of prolyl 4-hydroxylases to increase Type I collagen maturation. In addition, we found that LY83583 activated prolyl 4-hydrolases differed from ascorbate-activated prolyl 4-hydroxylase in two aspects: (1) LY83583 activated both P4HA1 and P4HA2 involved in collagen maturation whereas ascorbate mainly stimulated P4HA1 in collagen maturation; (2) LY83583 did not induce N259 glycosylation on P4HA1 as ascorbate did. The mechanisms remain to be investigated.
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http://dx.doi.org/10.1016/j.bbrc.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442856PMC
September 2020

RNA-Binding Protein Rbm24 as a Multifaceted Post-Transcriptional Regulator of Embryonic Lineage Differentiation and Cellular Homeostasis.

Cells 2020 08 12;9(8). Epub 2020 Aug 12.

Developmental Biology Laboratory, CNRS-UMR7622, IBPS, Sorbonne University, 75005 Paris, France.

RNA-binding proteins control the metabolism of RNAs at all stages of their lifetime. They are critically required for the post-transcriptional regulation of gene expression in a wide variety of physiological and pathological processes. Rbm24 is a highly conserved RNA-binding protein that displays strongly regionalized expression patterns and exhibits dynamic changes in subcellular localization during early development. There is increasing evidence that it acts as a multifunctional regulator to switch cell fate determination and to maintain tissue homeostasis. Dysfunction of Rbm24 disrupts cell differentiation in nearly every tissue where it is expressed, such as skeletal and cardiac muscles, and different head sensory organs, but the molecular events that are affected may vary in a tissue-specific, or even a stage-specific manner. Recent works using different animal models have uncovered multiple post-transcriptional regulatory mechanisms by which Rbm24 functions in key developmental processes. In particular, it represents a major splicing factor in muscle cell development, and plays an essential role in cytoplasmic polyadenylation during lens fiber cell terminal differentiation. Here we review the advances in understanding the implication of Rbm24 during development and disease, by focusing on its regulatory roles in physiological and pathological conditions.
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http://dx.doi.org/10.3390/cells9081891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463526PMC
August 2020

Interleukin-17 Gene Polymorphism (Rs2275913 G/A, Rs763780 C/T) in Rheumatoid arthritis:Meta-analysis Based on Ethnicity.

Immunol Invest 2020 Jul 1:1-15. Epub 2020 Jul 1.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University , Hefei, Anhui, China.

Introduction: The association between interleukin()-17A and F gene polymorphism with rheumatoid arthritis (RA) were inconsistent among previous studies. This meta-analysis aimed to determine the association between A and F gene polymorphism with RA.

Methods: We searched Medline up to February 2020. Meta-analyses were performed for the comparisons of allele and multiple genetic models, including dominant, recessive, heterozygous, and homozygous models using fixed or random effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were utilized to assess the potential relationship.

Results: A total of 2315 confirmed cases and 2342 controls were included from eligible 10 case-controls studies. Meta analysis suggested that rs2275913 G allele increased the risk of RA in Caucasians (G vs A: OR = 1.14, 95% CI = 1.00-1.29, = .044), but not in Mongolians ( > .05). Pooled analysis suggested that a significant associations between rs763780 C allele with RA susceptibility (C vs T: OR = 1.83, 95% CI = 1.13-2.97, = .014). Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to RA risk in two races ( < .001). TSA plot revealed that the present study sufficient to draw a conclusion.

Conclusions: This meta-analysis demonstrates A and F genes play a significant role in RA, but its role in Mongolian populations needs further exploration.
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http://dx.doi.org/10.1080/08820139.2020.1786397DOI Listing
July 2020

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: a randomized, double-blind, controlled phase III clinical trial in children aged 6-35 months in China.

Hum Vaccin Immunother 2020 07 29;16(7):1691-1698. Epub 2020 Apr 29.

Clinical Trials Assessment Department, Jiangsu Provincial Center for Disease Control and Prevention , Nanjing, China.

Mismatch between circulating influenza B viruses and vaccine strains occurs frequently. In a randomized, double-blind, controlled phase III clinical study, healthy children aged 6-35 months were randomized into three groups at a ratio of 2:1:1, received two doses of quadrivalent influenza vaccines (QIVs) or licensed trivalent influenza vaccines (TIVs). The primary objective was to evaluate the non-inferiority immunogenicity of QIV compared with the two TIVs, containing B/Victoria or B/Yamagata strain. Safety information was collected for 28 days after each vaccination. Serious adverse events (SAEs) were monitored for 6 months after the second vaccination. A total of 2146 subjects (QIV: 1069, TIV-Vic: 540, TIV-Yam: 537) were enrolled in this study. QIV was found non-inferior to TIVs for shared strains (A/H1N1 and A/H3N2) and corresponding BY strain based on hemagglutination inhibition (HI) antibodies 28 days after the second dose of vaccination. The resulted geometric mean titer (GMT) ratios (QIV/TIV) were 0.98 (0.89, 1.07) for H1N1, 0.95 (0.85, 1.05) for H3N2 and 0.89 (0.81, 0.98) for BY. And the seroconversion rate differences (QIV-TIV) were -0.46% (-3.24%, 2.31%) for H1N1, -1.95% (-5.54%, 1.65%) for H3N2 and -3.58% (-8.11%, 0.95%) for BY. The BV strain in QIV did not reach the non-inferiority criteria, with GMT of 1:52.25 (vs. 1:61.02 of TIV-Vic) and seroconversion rate of 59.49% (vs. 66.85% of TIV-Vic). No increased safety concerns occurred in QIV group. Candidate QIV can provide good protection for children aged 6 to 35 months, and its immunogenicity and safety were proved.

Clinical Trials Registration: ClinicalTrials.gov number: NCT03859141.
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http://dx.doi.org/10.1080/21645515.2020.1721994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482894PMC
July 2020

L-DOPA-elicited abnormal involuntary movements in the rats damaged severely in substantia nigra by 6-hydroxydopamine.

Ann Palliat Med 2020 May 7;9(3):947-956. Epub 2020 Apr 7.

Department of Neurology, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China.

Background: Dyskinesia of rat models can occur in several conditions: acute levodopa (L-DOPA) administration provided that the drug dose is sufficiently high and/or that the nigrostriatal dopamine (DA) pathway is seriously damaged, and repeated L-DOPA administration which could cause a reduction of the dyskinesia-threshold dose, a progressive aggravation and an increasing incidence of dyskinesia. Therefore, if the damage of the nigrostriatal DA pathway is extremely severe, what abnormal movements can be elicited by first injecting L-DOPA or other dopaminergic agonists? The problem deserves exploring.

Methods: Rat models with damage of varying severity were divided into three groups: the serious lesion [induced by 40 µg 6-hydroxydopamine (6-OHDA), two injected coordinates including substantia nigra (SN) and medial forebrain bundle], the moderate lesion (20 µg 6-OHDA, a coordinate in SN) and the control. Three weeks after lesion, the Rota Rad test and Cylinder test were performed to assess the motor activities of rat models, the abnormal involuntary movements (AIMs) elicited by L-DOPA or apomorphine (APO) were observed, and the dopaminergic degeneration in SN and striatum was determined.

Results: Both seriously lesioned rats and the moderately were observed to exhibit a significant decrease in motor activities. In the rats with a serious lesion, scarcely any dopaminergic neurons were present in the SN, tissue DA level decreased by 99% in the striatum, and both L-DOPA and APO could elicit AIMs and rotational movements. In the rats with the moderate lesion, only rotation movements could be elicited. The rotation speed of moderately lesioned rats was 9 turns/min, but that of seriously was only 4.5 turns/min elicited by APO.

Conclusions: Both dyskinesia and rotation movement are the specific expressions elicited by L-DOPA or APO in rats whose SN is damaged by 6-OHDA. Dyskinesia reflects more severe damage than rotation movement.
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http://dx.doi.org/10.21037/apm.2020.03.32DOI Listing
May 2020

Identification of 10 differently expressed lncRNAs as prognostic biomarkers for prostate adenocarcinoma.

Math Biosci Eng 2019 12;17(3):2037-2047

Department of Urology, Jining NO.1 People's hospital, 99 Shixian Road, Jining High-tech Zone, Jining 272000, China.

Prostate adenocarcinoma (PRAD) is one of the most frequently diagnosed cancer in males. Previous studies had demonstrated long non-coding RNAs (lncRNAs) played crucial roles in human cancers. In present study, we reported ten disease-free survival time related lncRNAs in PRAD, including RP11-468E2.5, GS1-393G12.13, CTD-2228K2.7, RP11-783K16.13, RP11-631N16.4, CTC-435M10.12, RP11-1109F11.5, RP11-228B15.4, RP11-496I9.1, and RP11-95O2.5. Higher expression of these lncRNAs significantly correlates to shorter DFS time in patients with PRAD. We next constructed lncRNAs regulating PPI networks in PRAD. Bioinformatics analysis revealed these DFS-related lncRNAs were associated with the regulation of cell cycle, glucose metabolic process, histone modification, and RNA splicing. AR and SPOP were identified to be involved in regulating these lncRNAs expression in PRAD. The prognostic value and molecular functions of these lnRNAs in human diseases remained largely unknown. We thought this study for the first time demonstrated that they could act as novel potential biomarkers for PRAD.
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http://dx.doi.org/10.3934/mbe.2020108DOI Listing
December 2019

Serum Levels of Hepcidin in Rheumatoid Arthritis and Its Correlation with Disease Activity and Anemia: A Meta-analysis.

Immunol Invest 2021 Feb 26;50(2-3):243-258. Epub 2020 Mar 26.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University , Hefei, Anhui, China.

Present studies on serum hepcidin levels in patients with rheumatoid arthritis (RA) are inconsistent. We aimed to synthetically evaluate the relationship between hepcidin and RA, and the correlation of serum hepcidin levels and RA disease activity as well as anemia associated with RA. Multiple electronic databases were searched. Pooled standard mean difference (SMD) with 95% confidence interval (CI) and correlation coefficients between hepcidin levels and rheumatoid factor (RF), disease activity for 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) were calculated. Totally, 13 articles were available for this meta-analysis. The results revealed that serum levels of hepcidin were higher in RA patients compared to healthy controls (SMD = 0.573, 95% CI = 0.317 to 0.829, p < .001); RA patients with anemia had higher serum hepcidin levels than RA patients without anemia (SMD = 0.400, 95% CI = 0.080 to 0.720, p = .014); RA patients with pure ACD had higher serum hepcidin levels than RA patients with ACD and IDA (SMD = 0.658, 95% CI = 0.018 to 1.299, p = .044). Moreover, the result of correlation coefficients identified a significant positive correlation between hepcidin levels and RF, DAS28 as well as ESR. Serum hepcidin levels may be closely associated with the development of RA.
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http://dx.doi.org/10.1080/08820139.2020.1742731DOI Listing
February 2021

Rbm24 controls poly(A) tail length and translation efficiency of mRNAs in the lens via cytoplasmic polyadenylation.

Proc Natl Acad Sci U S A 2020 03 13;117(13):7245-7254. Epub 2020 Mar 13.

Medical Research Institute, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;

Lens transparency is established by abundant accumulation of crystallin proteins and loss of organelles in the fiber cells. It requires an efficient translation of lens messenger RNAs (mRNAs) to overcome the progressively reduced transcriptional activity that results from denucleation. Inappropriate regulation of this process impairs lens differentiation and causes cataract formation. However, the regulatory mechanism promoting protein synthesis from lens-expressed mRNAs remains unclear. Here we show that in zebrafish, the RNA-binding protein Rbm24 is critically required for the accumulation of crystallin proteins and terminal differentiation of lens fiber cells. In the developing lens, Rbm24 binds to a wide spectrum of lens-specific mRNAs through the RNA recognition motif and interacts with cytoplasmic polyadenylation element-binding protein (Cpeb1b) and cytoplasmic poly(A)-binding protein (Pabpc1l) through the C-terminal region. Loss of Rbm24 reduces the stability of a subset of lens mRNAs encoding heat shock proteins and shortens the poly(A) tail length of mRNAs encoding lens structural components, thereby preventing their translation into functional proteins. This severely impairs lens transparency and results in blindness. Consistent with its highly conserved expression in differentiating lens fiber cells, the findings suggest that vertebrate Rbm24 represents a key regulator of cytoplasmic polyadenylation and plays an essential role in the posttranscriptional control of lens development.
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http://dx.doi.org/10.1073/pnas.1917922117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132282PMC
March 2020

Downregulation of lysyl oxidase in venous malformations: Association with vascular destabilization and sclerotherapy.

J Dermatol 2020 May 11;47(5):518-526. Epub 2020 Mar 11.

Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Venous malformations (VM) are localized defects in vascular morphogenesis manifested by dilated venous channels with reduced perivascular cell coverage. As a vital enzyme for extracellular matrix (ECM) deposition, lysyl oxidase (LOX) plays important roles in vascular development and diseases. However, the expression and significance of LOX are unknown in VM. Herein, 22 VM specimens and eight samples of normal skin tissues were evaluated immunohistochemically for the expression of LOX, α-smooth muscle cell actin (α-SMA) and transforming growth factor-β (TGF-β). In vitro studies on human umbilical vein endothelial cells (HUVEC) were employed for determining potential mechanisms. Our results showed that LOX expression was significantly reduced in VM compared with normal skin tissues, in parallel with attenuated perivascular α-SMA cell coverage and TGF-β downregulation in VM. Further correlation analysis indicated that LOX expression was positively correlated with perivascular α-SMA cell coverage and TGF-β expression in VM. Moreover, marked elevation of LOX, TGF-β and α-SMA was observed in bleomycin-treated VM samples. Furthermore, our in vitro data demonstrated that both recombinant TGF-β and bleomycin induced obvious increase of LOX expression and activity and a concomitant increase in ECM components in HUVEC, which could be reversed by LOX inhibition. To our best knowledge, this study revealed for the first time the downregulation of LOX in VM and its correlation with vascular destabilization and TGF-β-induced endothelial ECM deposition. Moreover, our results highlighted that LOX may be implicated in the sclerotherapy of VM and holds promise as a therapeutic target.
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http://dx.doi.org/10.1111/1346-8138.15297DOI Listing
May 2020

Association between IL-17A and IL-17F gene polymorphism and susceptibility in inflammatory arthritis: A meta-analysis.

Clin Immunol 2020 04 5;213:108374. Epub 2020 Mar 5.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

Objectives: The association between Interleukin (IL)-17A and IL-17F gene polymorphism with inflammatory arthritis were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17F gene polymorphism with ankylosing spondylitis (AS), osteoarthritis (OA) and rheumatoid arthritis (RA).

Methods: We searched Medline up to August 2019. The summary Odds Ratio (OR) with corresponding 95% confidence intervals (CIs) was calculated to evaluate the relationship between IL-17A and IL-17F gene polymorphism with genetic susceptibility of AS, OA and RA.

Results: A total of 19 studies with 5298 cases and 5675 healthy controls were included. There were significant associations between rs2275913 G allele with OA, RA susceptibility (P < .05) but not AS. Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to AS and OA in Caucasian populations (P < .001) but not Mongolians. A significant association between rs763780 and RA susceptibility was detected in Caucasian populations (P < .05).

Conclusion: IL-17F gene rs763780 C allele confers increased risk of inflammatory arthritis in Caucasians; IL-17A gene rs2275913 G allele are protective for OA susceptibility in Mongolians. More well-designed studies with larger sample size are needed to elucidate the role of IL-17A gene rs2275913 G allele in inflammatory arthritis, especially AS.
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http://dx.doi.org/10.1016/j.clim.2020.108374DOI Listing
April 2020

B7-H3: A promising therapeutic target for autoimmune diseases.

Cell Immunol 2020 06 21;352:104077. Epub 2020 Feb 21.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

B7-H3 as a newly identified costimulatory molecule that belongs to B7 ligand family, is broadly expressed in both lymphoid and non-lymphoid tissues. The overexpression of B7-H3 has been verified to be correlated with the poor prognosis and poor clinical outcome of several human cancers. In recent years, researchers reveal that B7-H3 is involved in the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), Sjögren's syndrome (SS), ankylosing spondylitis (AS), etc. In this review, we will discuss the biological function of B7-H3 and summarize the progress made over past years regarding its role in the occurrence and development of autoimmune diseases. The insights gained from these findings could serve as the foundation for future therapies of these diseases.
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http://dx.doi.org/10.1016/j.cellimm.2020.104077DOI Listing
June 2020

Reduced expression of CENP-E contributes to the development of hepatocellular carcinoma and is associated with adverse clinical features.

Biomed Pharmacother 2020 Mar 24;123:109795. Epub 2019 Dec 24.

Central Laboratory, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, PR China; School of Life Sciences, University of Technology Sydney, Broadway, NSW 2007, Australia. Electronic address:

Human kinesin centromere-associated protein E (CENP-E), one of spindle checkpoint proteins, has been identified as a tumor suppressor in several types of cancer, however, its role in hepatocarcinogenesis remains unknown. Here we investigated the role of CENP-E in human hepatocellular carcinoma (HCC) employing HCC cell lines (Hep3B, SMMC7721, and QGY7701), animal models, and patient's clinical samples and data. We demonstrated that down-regulation of CENP-E by CENP-E-silencing shRNAs significantly promoted HCC proliferation/growth both in vitro and in vivo. Further studies found that CENP-E suppressed the proliferation of HCC cells by halting cell cycle progression at the G1-S phase and accelerating cell apoptosis. Analyses of HCC patient samples and clinical data revealed that CENP-E was significantly down-regulated in HCC tissues and low CENP-E expression was significantly associated with patient's adverse clinicopathological features: poor prognosis, advanced TNM stage, metastasis, and larger tumor size. Multivariate analysis indicated that CENP-E was an independent prognostic factor predicting outcomes of advanced HCC patients. Our data suggest that loss of CENP-E contributes to HCC development and is strongly associated with adverse HCC clinical pathology. Thus, CENP-E could be a novel target for new treatments and a useful prognostic biomarker for HCC patients.
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http://dx.doi.org/10.1016/j.biopha.2019.109795DOI Listing
March 2020

Melanoma migration is promoted by prion protein via Akt-hsp27 signaling axis.

Biochem Biophys Res Commun 2020 03 20;523(2):375-381. Epub 2019 Dec 20.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, 78 Hengzhigang Road, Guangzhou, 510095, China. Electronic address:

Patients with metastatic melanoma have a poorer prognosis. Prion protein (PrP) in melanoma is known to play an important role in cancer cell migration and invasion by interacting with filamin A (FLNa), a cytolinker protein. To investigate if PrP may contribute to cancer cell mobility independent of its binding to FLNa, we knocked out PRNP in M2 melanoma cell, which lacked FLNa expression. We found that deletion of PRNP in M2 significantly reduced its motility. When PRNP was deleted, the level of Akt was decreased. As a consequence, phosphorylation of small heat shock protein (hsp27) was also reduced, which resulted in polymerization of F-actin rendering the cells less migratory. Accordingly, when PrP was re-expressed in PRNP null M2 cells, the mobility of the recurred cells was rescued, so were the expression levels of Akt and phosphorylated hsp27, resulting in a decrease in the polymerization of F-actin. These results revealed that PrP can play a FLNa independent role in cytoskeletal organization and tumor cell migration by modulating Akt-hsp27-F-actin axis.
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http://dx.doi.org/10.1016/j.bbrc.2019.12.042DOI Listing
March 2020

Gait Characteristics of Children with Spastic Cerebral Palsy during Inclined Treadmill Walking under a Virtual Reality Environment.

Appl Bionics Biomech 2019 19;2019:8049156. Epub 2019 Aug 19.

Department of Exercise Sciences, The University of Auckland, New Zealand.

Objective: To investigate gait characteristics in children with spastic cerebral palsy during inclined treadmill walking under a virtual reality environment.

Methods: Ten (CP) children and ten (TD) children were asked to walk at their comfortable speed on a treadmill at a ground level and 10° inclined. Three-dimensional kinematic data and ground reaction force data were captured in a computer-assisted rehabilitation environment system. Kinetic parameters and dynamic balance parameters were calculated using a standard biomechanical approach.

Results: During uphill walking, both groups decreased walking speed and stride length and increased peak pelvis tilt, ankle dorsiflexion, and hip flexion. Compared with TD children, CP children had decreased walking speed and stride length, decreased peak hip abduction moment, increased stance phase percentage, increased peak ankle dorsiflexion and knee flexion, and increased peak hip extension moment. The peak trunk rotation angle, ankle angle at initial contact, and stride length showed a significant group∗walking condition interaction effect.

Conclusions: CP children showed similar adjustments for most gait parameters during uphill walking as TD children. With a lower walking speed, CP children could maintain similar dynamic balance as TD children. Uphill walking magnifies the existing abnormal gait patterns of the cerebral palsy children. We suggest that during a treadmill training with an inclination, the walking speed should be carefully controlled in the case of improving peak joint loading too much.
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http://dx.doi.org/10.1155/2019/8049156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721380PMC
August 2019

Knockdown of KCNQ1OT1 Suppresses Cell Invasion and Sensitizes Osteosarcoma Cells to CDDP by Upregulating DNMT1-Mediated Kcnq1 Expression.

Mol Ther Nucleic Acids 2019 Sep 27;17:804-818. Epub 2019 Jun 27.

The 1st Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R. China. Electronic address:

Osteosarcoma is a malignant bone tumor, with a high incidence worldwide. The involvement of long non-coding RNAs (lncRNAs) in cancers and their molecular association with the progression of osteosarcoma have been previously discussed. We conducted the present study to examine the effect of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) on osteosarcoma cell invasion and chemosensitivity to cisplatin (CDDP). After determination of the expression of Kcnq1 in osteosarcoma tissues and cells, the plasmids with overexpression or knockdown KCNQ1OT1 were introduced into the cells to aid the identification of cell proliferation, migration, invasion, chemosensitivity to CDDP, and apoptosis. Then, the interaction between KCNQ1OT1 and the Kcnq1/DNA methyltransferase 1 (DNMT1) axis was evaluated by measuring the level of Kcnq1 promoter region methylation and DNMT1 enrichment of the Kcnq1 promoter region. Low Kcnq1 expression and high KCNQ1OT1 expression were shown in osteosarcoma tissues and cells. Kcnq1 was negatively mediated by KCNQ1OT1 via DNMT1. The overexpression of Kcnq1 or knockdown of KCNQ1OT1 inhibited the proliferation, migration, and invasion, and it promoted the chemosensitivity to CDDP and apoptosis of MG-63 cells and its CDDP-resistant cell lines. Moreover, the same trend was observed in the cells following methylation inhibitor treatment. Collectively, knockdown of KCNQ1OT1 can inhibit the osteosarcoma progression through the Kcnq1/DNMT1 axis.
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http://dx.doi.org/10.1016/j.omtn.2019.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716066PMC
September 2019

Sensitive Method for Reliable Quantification of Sulfane Sulfur in Biological Samples.

Anal Chem 2019 09 4;91(18):11981-11986. Epub 2019 Sep 4.

State Key Laboratory of Microbial Technology , Shandong University , Qingdao 266237 , People's Republic of China.

Sulfane sulfur has been recognized as a common cellular component, participating in regulating enzyme activities and signaling pathways. However, the quantification of total sulfane sulfur in biological samples is still a challenge. Here, we developed a method to address the need. All tested sulfane sulfur reacted with sulfite and quantitatively converted to thiosulfate when heated at 95 °C in a solution of pH 9.5 for 10 min. The assay condition was also sufficient to convert total sulfane sulfur in biological samples to thiosulfate for further derivatization and quantification. We applied the method to detect sulfane sulfur contents at different growth phases of bacteria, yeast, mammalian cells, and zebrafish. Total sulfane sulfur contents in all of them increased in the early stage, kept at a steady state for a period, and declined sharply in the late stage of the growth. Sulfane sulfur contents varied in different species. For , growth media also affected the sulfane sulfur contents. Total sulfane sulfur contents from different organs of mouse and shrimp were also detected, varying from 1 to 10 nmol/(mg of protein). Thus, the new method is suitable for the quantification of total sulfane sulfur in biological samples.
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http://dx.doi.org/10.1021/acs.analchem.9b02875DOI Listing
September 2019

Arc-support Line Segments Revisited: An Efficient High-quality Ellipse Detection.

IEEE Trans Image Process 2019 Aug 15. Epub 2019 Aug 15.

Over the years many ellipse detection algorithms spring up and are studied broadly, while the critical issue of detecting ellipses accurately and efficiently in real-world images remains a challenge. In this paper, we propose a valuable industry-oriented ellipse detector by arc-support line segments, which simultaneously reaches high detection accuracy and efficiency. To simplify the complicated curves in an image while retaining the general properties including convexity and polarity, the arc-support line segments are extracted, which grounds the successful detection of ellipses. The arc-support groups are formed by iteratively and robustly linking the arc-support line segments that latently belong to a common ellipse. Afterward, two complementary approaches, namely, locally selecting the arc-support group with higher saliency and globally searching all the valid paired groups, are adopted to fit the initial ellipses in a fast way. Then, the ellipse candidate set can be formulated by hierarchical clustering of 5D parameter space of initial ellipses. Finally, the salient ellipse candidates are selected and refined as detections subject to the stringent and effective verification. Extensive experiments on three public datasets are implemented and our method achieves the best F-measure scores compared to the state-of-the-art methods. The source code is available at https://github.com/AlanLuSun/High-quality-ellipse-detection.
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http://dx.doi.org/10.1109/TIP.2019.2934352DOI Listing
August 2019

Fluorinated Low-Dimensional Ruddlesden-Popper Perovskite Solar Cells with over 17% Power Conversion Efficiency and Improved Stability.

Adv Mater 2019 Sep 5;31(37):e1901673. Epub 2019 Aug 5.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

Low-dimensional Ruddlesden-Popper perovskites (RPPs) exhibit excellent stability in comparison with 3D perovskites; however, the relatively low power conversion efficiency (PCE) limits their future application. In this work, a new fluorine-substituted phenylethlammonium (PEA) cation is developed as a spacer to fabricate quasi-2D (4FPEA) (MA) Pb I (n = 5) perovskite solar cells. The champion device exhibits a remarkable PCE of 17.3% with a J of 19.00 mA cm , a V of 1.16 V, and a fill factor (FF) of 79%, which are among the best results for low-dimensional RPP solar cells (n ≤ 5). The enhanced device performance can be attributed as follows: first, the strong dipole field induced by the 4-fluoro-phenethylammonium (4FPEA) organic spacer facilitates charge dissociation. Second, fluorinated RPP crystals preferentially grow along the vertical direction, and form a phase distribution with the increasing n number from bottom to the top surface, resulting in efficient charge transport. Third, 4FPEA-based RPP films exhibit higher film crystallinity, enlarged grain size, and reduced trap-state density. Lastly, the unsealed fluorinated RPP devices demonstrate superior humidity and thermal stability. Therefore, the fluorination of the long-chain organic cations provides a feasible approach for simultaneously improving the efficiency and stability of low-dimensional RPP solar cells.
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http://dx.doi.org/10.1002/adma.201901673DOI Listing
September 2019

Cul4a promotes zebrafish primitive erythropoiesis via upregulating scl and gata1 expression.

Cell Death Dis 2019 05 17;10(6):388. Epub 2019 May 17.

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, School of Basic Medical Sciences, Shandong University, 250012, Jinan, China.

CUL4A and CUL4B are closely related members in Cullin family and can each assemble a Cullin-RING E3 ligase complex (Cullin-RING Ligase 4A or 4B, CRL4A, or CRL4B) and participate in a variety of biological processes. Previously we showed that zebrafish cul4a, but not cul4b, is essential for cardiac and pectoral fin development. Here, we have identified cul4a as a crucial regulator of primitive erythropoiesis in zebrafish embryonic development. Depletion of cul4a resulted in a striking reduction of erythroid cells due to the inhibition of erythroid differentiation. Transcript levels for early hematopoietic regulatory genes including scl, lmo2, and gata1 are significantly reduced in cul4a-deficient embryos. Mechanistically, we demonstrated that scl and gata1, the central regulators of primitive hematopoiesis for erythroid determination, are transcriptionally upregulated by cul4a. These findings demonstrate an important role for cul4a in primitive erythropoiesis and may bear implications in regeneration medicine of anemia and related diseases.
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http://dx.doi.org/10.1038/s41419-019-1629-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525236PMC
May 2019

Binding between Prion Protein and Aβ Oligomers Contributes to the Pathogenesis of Alzheimer's Disease.

Virol Sin 2019 Oct 15;34(5):475-488. Epub 2019 May 15.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.

A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases, such as prion diseases and Alzheimer's disease (AD). Like prion diseases, AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential. Although it remains elusive how protein aggregation leads to AD, it is becoming clear that cellular prion protein (PrP) plays an important role in AD pathogenesis. Here, we briefly reviewed AD pathogenesis and focused on recent progresses how PrP contributed to AD development. In addition, we proposed a potential mechanism to explain why infectious agents, such as viruses, conduce AD pathogenesis. Microbe infections cause Aβ deposition and upregulation of PrP, which lead to high affinity binding between Aβ oligomers and PrP. The interaction between PrP and Aβ oligomers in turn activates the Fyn signaling cascade, resulting in neuron death in the central nervous system (CNS). Thus, silencing PrP expression may turn out be an effective treatment for PrP dependent AD.
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http://dx.doi.org/10.1007/s12250-019-00124-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814678PMC
October 2019