Publications by authors named "Xiu Juan Zhang"

68 Publications

Comparison of the triglyceride glucose index and blood leukocyte indices as predictors of metabolic syndrome in healthy Chinese population.

Sci Rep 2021 May 11;11(1):10036. Epub 2021 May 11.

Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.

Triglyceride glucose (TyG) index and inflammatory markers are reported to have a positive association with metabolic syndrome (MetS). However, no previous study has assessed the value of TyG index and inflammatory markers as predictors of metabolic syndrome in the same study. This study looks at the comparison of the triglyceride index and blood leukocyte indices as predictors of metabolic syndrome in the Chinese population. The study cohort involved 1542 Chinese population without metabolic syndrome. The subjects underwent comprehensive routine health examination in 2011 and returned for a follow-up examination in 2016. Metabolic syndrome was defined according to Chinese Diabetes Society criteria, using body mass index for the replacement of waist circumference. TyG index, total leukocytes, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) were measured. Adjust d logistic models were used to assess the relationship between TyG index, blood leukocyte indices, and incident MetS. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of TyG index and blood leukocyte indices for MetS. Results from multivariate logistic regression analysis showed that, in the adjusted model, the subjects with the highest quartile of TyG index and neutrophils had a 3.894- and 1.663-fold increased incidence of MetS (P < 0.0001 and P = 0.027), respectively. No significant association was observed between total leukocytes, lymphocytes, NLR with incident MetS. ROC analysis showed that the AUC of TyG index and neutrophils were 0.674 and 0.568 for incident MetS, respectively. TyG index rather than blood leukocyte indices may have the strongest predictive value in MetS development over a 5-year period.
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http://dx.doi.org/10.1038/s41598-021-89494-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113526PMC
May 2021

Association of polymorphisms in , and with myopia progression and polygenic risk prediction in children.

Br J Ophthalmol 2021 Apr 2. Epub 2021 Apr 2.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Aims: To assess the association of single-nucleotide polymorphisms (SNPs) with myopia progression for polygenic risk prediction in children.

Methods: Six SNPs ( rs4373767, rs13382811, rs7744813, rs2073560, rs7839488 and rs524952) were analysed in 1043 school children, who completed 3-year follow-up, using TaqMan genotyping assays. SNP associations with progression in spherical equivalent (SE) were analysed by logistic regression. Polygenic risk scores (PRS) were applied for computing the sum of the risk alleles of multiple SNPs corresponding to myopia progression, weighted by the effect sizes of corresponding SNPs.

Results: rs524952 showed significant association with fast progression (OR=1.32, 95% CI 1.10 to 1.59; p=0.003) and rs7744813 had nominal association (OR=1.32, 95% CI 1.04 to 1.67; p=0.02). In quantitative traits locus analysis, rs524952 and rs7744813 were associated with progression in SE (β=-0.038 D/year, p=0.008 and β=-0.042 D/year, p=0.02) and axial elongation (β=0.016 mm/year, p=0.01 and β=0.017 mm/year, p=0.027). rs13382811 also showed nominal association with faster progression in SE (β=-0.041 D/year, p=0.02). PRS analysis showed that children with the highest PRS defined by rs13382811, rs7744813 and rs524952 had a 2.26-fold of increased risk of fast myopia progression (p=4.61×10). PRS was also significantly associated with SE progression (R=1.6%, p=3.15×10) and axial elongation (R=1.2%, p=2.6×10).

Conclusions: In this study, multi-tiered evidence suggested SNPs in , and as risk factors for myopia progression in children. Additional attention and appropriate interventions should be given for myopic children with high-risk PRS as defined by rs524952, rs7744813 and rs13382811.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318708DOI Listing
April 2021

Fish consumption, long-chain omega-3 fatty acids intake and risk of stroke: An updated systematic review and meta-analysis.

Asia Pac J Clin Nutr 2021 ;30(1):140-152

Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, P.R. China. Email:

Background And Objectives: Although fish consumption or omega-3 intake is associated with cardio- cerebrovascular disease including stroke, their correlation is still controversial. Therefore, this meta-analysis is to identify the relationship between the risk of stroke and fish consumption or omega-3 intake.

Methods And Study Design: We searched the PubMed, EMBASE and Cochrane Library databases as of May 2019. Multivariateadjusted risk ratios (RRs) with 95% confidence interval (CI) for stroke in different level intake of fish or Longchain omega-3 polyunsaturated fatty acids (LC ω3-PUFAs) were pooled using a random-effects meta-analysis. A dose-response analysis was conducted with the 2-stage generalized least-squares trend program.

Results: Our meta-analysis identified a total of 17 prospective cohort studies including 14986 strokes events in 672711 individuals. Meta-analysis revealed that the higher fish consumption was significantly associated with lower risk of stroke (RR=0.871, 95% CI: 0.779-0.975, p=0.016), especially with ischemic stroke (RR=0.808, 95% CI: 0.696- 0.937, p=0.005). Meantime, the combined RR of total stroke was 0.859 (95% CI: 0.769-0.959, p=0.007) for the highest versus lowest intake of LC ω3-PUFAs, and stratification analysis showed that higher LC ω3-PUFAs intake was associated with reduced stroke risk in women (RR=0.793, 95% CI: 0.706-0.891, p=0.000) but not in men. In addition, the dose-response analysis showed fish consumption with 1000g per month and LC ω3-PUFAs intake with 0.5g per month was associated with 17.3% (RR=0.927, 95% CI: 0.83-0.98) and 14% (RR=0.86, 95% CI: 0.78-0.95) lower risk of stroke, respectively.

Conclusions: Both fish consumption and LC ω3-PUFAs intake were negatively associated with the risk of stroke, especially in women, which suggest that increased intake of fishery products and LC ω3-PUFAs may benefit primary prevention of stroke.
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http://dx.doi.org/10.6133/apjcn.202103_30(1).0017DOI Listing
January 2021

PTPL1 suppresses lung cancer cell migration via inhibiting TGF-β1-induced activation of p38 MAPK and Smad 2/3 pathways and EMT.

Acta Pharmacol Sin 2021 Feb 3. Epub 2021 Feb 3.

Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Epithelial-mesenchymal transition (EMT) enables dissemination of neoplastic cells and onset of distal metastasis of primary tumors. However, the regulatory mechanisms of EMT by microenvironmental factors such as transforming growth factor-β (TGF-β) remain largely unresolved. Protein tyrosine phosphatase L1 (PTPL1) is a non-receptor protein tyrosine phosphatase that plays a suppressive role in tumorigenesis of diverse tissues. In this study we investigated the role of PTPL1/PTPN13 in metastasis of lung cancer and the signaling pathways regulated by PTPL1 in terms of EMT of non-small cell lung cancer (NSCLC) cells. We showed that the expression of PTPL1 was significantly downregulated in cancerous tissues of 23 patients with NSCLC compared with adjacent normal tissues. PTPL1 expression was positively correlated with overall survival of NSCLC patients. Then we treated A549 cells in vitro with TGF-β1 (10 ng/mL) and assessed EMT. We found that knockdown of PTPL1 enhanced the migration and invasion capabilities of A549 cells, through enhancing TGF-β1-induced EMT. In nude mice bearing A549 cell xenografts, knockdown of PTPL1 significantly promoted homing of cells and formation of tumor loci in the lungs. We further revealed that PTPL1 suppressed TGF-β-induced EMT by counteracting the activation of canonical Smad2/3 and non-canonical p38 MAPK signaling pathways. Using immunoprecipitation assay we demonstrated that PTPL1 could bind to p38 MAPK, suggesting that p38 MAPK might be a direct substrate of PTPL1. In conclusion, these results unravel novel mechanisms underlying the regulation of TGF-β signaling pathway, and have implications for prognostic assessment and targeted therapy of metastatic lung cancer.
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http://dx.doi.org/10.1038/s41401-020-00596-yDOI Listing
February 2021

The synthesis and anti-tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors.

Bioorg Med Chem Lett 2020 12 14;30(23):127556. Epub 2020 Sep 14.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

A series of novel 4-substituted phthalazinones as Aurora B kinase inhibitors was synthesized and evaluated the anti-proliferative activities against A549, HCT116, MCF-7 and HepG2 cells. 1-(4-(2-((4-Oxo-3,4-dihydrophthalazin-1-yl)amino)ethyl) phenyl)-3-(3-(trifluoromethyl)phenyl)urea (17b) exhibited the most potent anti-proliferative activity against HCT116 cells with IC value of 4.35 ± 1.21 μM, as well as the moderate Aurora B inhibitory activity with the IC value of 142 nM. Furthermore, 17b inhibited the phosphorylation of Aurora B on Thr232, leading to cell cycle arrest in the G2/M phase by down-regulating the expression of CyclinB1 and Cdc2 proteins, and apoptosis by up-regulating the expression of BAD and Bax proteins in HCT116 cells. In addition, a docking study revealed that 17b could form key hydrogen bonds with Ala173, Glu171 and Glu177 in Aurora B. All the results reveal that 17b is worthy of further development as an Aurora B kinase inhibitor.
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http://dx.doi.org/10.1016/j.bmcl.2020.127556DOI Listing
December 2020

Combined proteomics and transcriptomics reveal the genetic basis underlying the differentiation of skin appendages and immunity in pangolin.

Sci Rep 2020 09 3;10(1):14566. Epub 2020 Sep 3.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Science, Guangzhou, 510260, China.

Pangolin (Mains javanica) is an interesting endangered mammal with special morphological characteristics. Here, we applied proteomics and transcriptomics to explore the differentiation of pangolin skin appendages at two developmental stages and to compare gene expression profiles between abdomen hair and dorsal scale tissues. We identified 4,311 genes and 91 proteins differentially expressed between scale-type and hair-type tissue, of which 6 genes were shared by the transcriptome and proteome. Differentiation altered the abundance of hundreds of proteins and mRNA in the two types of skin appendages, many of which are involved in keratinocyte differentiation, epidermal cell differentiation, and multicellular organism development based on GO enrichment analysis, and FoxO, MAPK, and p53 signalling pathways based on KEGG enrichment analysis. DEGs in scale-type tissues were also significantly enriched in immune-related terms and pathways compared with that in hair-type tissues. Thus, we propose that pangolins have a normal skin innate immune system. Compared with the abdomen, the back skin of pangolins had more genes involved in the regulation of immune function, which may be an adaptive adjustment for the vulnerability of scaly skin to infection and injury. This investigation provides a scientific basis for the study of development and immunity of pangolin skin, which may be helpful in the protection of wild pangolin in China.
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http://dx.doi.org/10.1038/s41598-020-71513-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471334PMC
September 2020

Design, synthesis and biological evaluation of indole-2-one derivatives as potent BRD4 inhibitors.

Eur J Med Chem 2020 Dec 30;208:112780. Epub 2020 Aug 30.

School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address:

Bromodomain protein 4 (BRD4) plays a crucial role in transcriptional regulation and is considered to be a viable drug target for cancer treatment. Herein, we designed and synthesized a series of indole-2-one derivatives through scaffold hopping drug design. Most of the compounds showed potent BRD4 inhibitory activities and anti-proliferation activities in cancer cell lines. Especially, compound 12j exhibited excellent BRD4 inhibitory activities (BD1 IC = 19 nM, BD2 IC = 28 nM) and anti-proliferation potency with IC values of 4.75 μM and 1.35 μM in HT-29 and HL-60 cells, respectively. Additionally, docking studies showed that the hydrophobic pocket next to KAc region and WPF shelf were critical to the activity of the compound. Compound 12j could arrest the cell-cycle progression of HT-29 cells into the G1 phase and reduce the expression of c-Myc. Moreover, compound 12j exhibited favorable oral pharmacokinetic properties. All the results demonstrated that compound 12j was a potent BRD4 inhibitor and had merely potential for colon cancer treatment.
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http://dx.doi.org/10.1016/j.ejmech.2020.112780DOI Listing
December 2020

Willingness to pay for cataract surgery in baiyin district, northwestern China.

Ophthalmic Epidemiol 2021 Jun 21;28(3):205-212. Epub 2020 Aug 21.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To investigate willingness to pay for cataract surgery, and its associations, in Northwestern China.

Methods: Four hundred thirty-eight persons aged 50 years and above, diagnosed with cataract indicated for surgery, identified in an outreach screening program were included. Subjects were offered a willingness-to-pay interview for the maximal amount that the subjects would be willing to pay for a cataract surgery. Age, gender, literacy, education level, occupation, and annual household income were recorded.

Results: Among 328 (74.9%) subjects who completed the interview, 197 (60.1%) participants were willing to pay something for the cataract surgery (mean, 902.9 ± 856.7 renminbi[RMB], [US$ 145 ± 137]; median, 500RMB, US$ 78). Individuals with presenting visual acuity (PVA) in the worse eye ≤6/60 (OR: 2.1, 95% CI: 1.3-3.2) and a high annual household incomes (OR: 2.0, 95% CI: 0.9-4.6) were likely to be willing to pay for the surgery, as revealed in the regression models. Willingness to pay any amount for cataract surgery was more likely among literate persons (OR: 1.5, 95% CI: 1.0-2.4) and persons with non-agricultural occupation (OR: 1.8, 95% CI: 1.0-3.2).

Conclusions: The amount that subjects were willing to pay is significantly less than the current cost of cataract surgery (5000 RMB, US$320) in the area. Providing low-cost cataract surgery to patients in a financially sustainable manner is important to increase uptake of cataract surgery among rural residents in Northwest China.
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http://dx.doi.org/10.1080/09286586.2020.1812089DOI Listing
June 2021

Transcriptome analysis reveals the genetic basis underlying the development of skin appendages and immunity in hedgehog (Atelerix albiventris).

Sci Rep 2020 08 18;10(1):13920. Epub 2020 Aug 18.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangdong Academy of Science, Guangzhou, 510260, China.

The expression of hair features is an evolutionary adaptation resulting from interactions between many organisms and their environment. Elucidation of the mechanisms that underlie the expression of such traits is a topic in evolutionary biology research. Therefore, we assessed the de novo transcriptome of Atelerix albiventris at three developmental stages and compared gene expression profiles between abdomen hair and dorsal spine tissues. We identified 328,576 unigenes in our transcriptome, among which 4,435 were differentially expressed between hair- and spine-type tissues. Dorsal and abdomen skin tissues 5 days after birth were compared and the resulting DEGs were mainly enriched in keratin filament, epithelium cell differentiation, and epidermis development based on GO enrichment analysis, and tight junction, p53, and cell cycle signaling pathways based on KEGG enrichment analysis. MBP8, SFN, Wnt1 and KRT1 gene may involve in the development of hedgehog skin and its appendages. Strikingly, DEGs in hair-type tissues were also significantly enriched in immune-related terms and pathways with hair-type tissues exhibiting more upregulated immune genes than spine-type tissues. Our study provided a list of potential genes involved in skin appendage development and differentiation in A. albiventris, and the candidate genes provided valuable information for further studies of skin appendages.
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http://dx.doi.org/10.1038/s41598-020-70844-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435191PMC
August 2020

LncRNA KCNQ1OT1 regulates the invasion and migration of hepatocellular carcinoma by acting on S1PR1 through miR-149.

Cancer Gene Ther 2020 Aug 5. Epub 2020 Aug 5.

Department of Physiology, Guangdong Medical University, 523808, Dongguan, P.R. China.

The aim of this study was to investigate the effect of lncRNA KCNQ1OT1 on HCC and to explore the possible underlying mechanisms. The expression levels of KCNQ1OT1, miR-149 and S1PR1 were detected by qRT-PCR assay. A dual luciferase reporter assay was used to detect the interaction between KCNQ1OT1 and miR-149, as well as miR-149 and S1PR1. The interaction between KCNQ1OT1 and miR-149 was further investigated by RNA pull-down assay. Wound healing assays and Transwell assays were carried out to determine cell migration and invasion. A xenograft tumour assay was used to validate the role of KCNQ1OT1 in vivo. KCNQ1OT1 and S1PR1 were significantly increased, but miR-149 was decreased in HCC cells. Luciferase reporter assays and RNA pull-down assays revealed that KCNQ1OT1 directly targeted miR-149. In addition, miR-149 bound to the 3'-UTR of S1PR1. Knockdown of KCNQ1OT1 or overexpression of miR-149 inhibited the invasion and migration of HCC cells. However, suppression of miR-149 could abrogate the effect of KCNQ1OT1 knockdown on the invasion and migration abilities of HCC cells. In vivo assays showed that KCNQ1OT1 knockdown suppressed tumour growth. This work suggests that lncRNA KCNQ1OT1 might act as a potential therapeutic target in HCC.
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http://dx.doi.org/10.1038/s41417-020-0203-xDOI Listing
August 2020

Association of Optical Coherence Tomography Angiography Metrics With Detection of Impaired Macular Microvasculature and Decreased Vision in Amblyopic Eyes: The Hong Kong Children Eye Study.

JAMA Ophthalmol 2020 08;138(8):858-865

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong.

Importance: Microvascular abnormalities in amblyopia are becoming evident with high-resolution imaging, such as optical coherence tomography angiography (OCT-A); however, to our knowledge, the clinical significance and use of these findings are unknown.

Objective: To assess changes in quantitative OCT-A metrics in amblyopic eyes and explore their association with visual acuity in children.

Design, Setting, And Participants: This population-based nested case-control study included children aged 6 to 8 years who were consecutively recruited between January 2016 and July 2017 from the population-based Hong Kong Children Eye Study (HKCES) at the Chinese University of Hong Kong Eye Centre. All participants underwent OCT-A with a swept-source OCT and detailed ophthalmic investigations. Macular microvasculature of the superficial capillary plexus was quantified by a customized automated image analysis program. A multivariable linear regression was conducted to evaluate the differences in OCT-A metrics between amblyopic and nonamblyopic eyes after adjustment for all known confounders. Data analysis was conducted from September to November 2018.

Main Outcomes And Measures: Differences in OCT-A metric (foveal avascular zone [FAZ]) area, FAZ circularity, vessel density, vessel diameter index, and fractal dimension between amblyopic and nonamblyopic eyes.

Results: There were 30 participants with amblyopia (mean [SD] age, 7.57 [1.2] years; 16 girls [53.3%]) and 1045 controls (mean [SD] age, 7.65 [1.0] years; 580 girls [55.5%]) in this cohort. Compared with control eyes, amblyopic eyes had decreased FAZ circularity (-0.058; 95% CI, -0.096 to -0.021, P = .002), decreased fractal dimension (-0.014; 95% CI, -0.024 to -0.003; P = .01), and increased vessel diameter index (0.002; 95% CI, 0.002 to 0.003; P < .001). A difference was not identified between FAZ area and vessel density. LogMAR visual acuity was associated with FAZ circularity (sβ, -0.133; P < .001) and vessel diameter index (sβ, 0.097; P = .001) but not with vessel density nor FAZ area.

Conclusions And Relevance: The results of this population-based study in children supports the presence of macular microvascular abnormalities in amblyopic eyes. Such changes as measured by OCT-A metrics are associated with visual acuity, inferring retinal involvement in the development of amblyopia and suggesting a potential role of quantitative OCT-A metrics in the diagnosis and recognition of amblyopia.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.2220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317658PMC
August 2020

Protein tyrosine phosphatase L1 represses endothelial-mesenchymal transition by inhibiting IL-1β/NF-κB/Snail signaling.

Acta Pharmacol Sin 2020 Aug 9;41(8):1102-1110. Epub 2020 Mar 9.

Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Endothelial-mesenchymal transition (EnMT) plays a pivotal role in various diseases, including pulmonary hypertension (PH), and transcription factors like Snail are key regulators of EnMT. In this study we investigated how these factors were regulated by PH risk factors (e.g. inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs). We showed that treatment with interleukin 1β (IL-1β) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL-1β or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens. Our findings provide novel insights into the regulatory mechanisms of EnMT, and have implications for identifying new therapeutic targets for clinical PH.
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http://dx.doi.org/10.1038/s41401-020-0374-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470836PMC
August 2020

Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors.

Bioorg Med Chem Lett 2020 02 13;30(3):126885. Epub 2019 Dec 13.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a showed the moderate to high anti-proliferative activities against A549 (IC = 12.05 ± 0.45 μM), HCT-116 (IC = 1.31 ± 0.41 μM) and MCF-7 (IC = 20.53 ± 6.13 μM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor.
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http://dx.doi.org/10.1016/j.bmcl.2019.126885DOI Listing
February 2020

Diagnostic Accuracy of Rapid Assessment of Avoidable Blindness: A Population-based Assessment.

Am J Ophthalmol 2020 05 14;213:235-243. Epub 2019 Dec 14.

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China; Project Vision Charitable Foundation, Hong Kong, China. Electronic address:

Objectives: To evaluate the diagnostic accuracy of rapid assessment of avoidable blindness (RAAB).

Design: Population-based diagnostic accuracy study.

Methods: A total of 2145 (95.3%, 2145/2250) subjects aged 50 years and older who participated in the RAAB survey were included. All the recruited participants underwent ophthalmic examination according to the RAAB protocol and then were reexamined with instruments in a mobile eye clinic set up in a village center on the same day. Examination in the mobile clinic included standardized visual acuity (VA) tests using logMAR charts, refraction, slit-lamp biomicroscopy, and dilated fundal examination with a binocular indirect ophthalmoscope. Blindness and economic blindness were defined as VA in the better-seeing eye <3/60 and <6/60, respectively. Visual impairment (VI) was defined as VA <6/18 in the better eye. The primary cause of blindness and VI was defined according to the cause of VI in the participant's better eye.

Main Outcome Measures: The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) of receiver operating characteristics of RAAB for detection of blindness and the principal causes of VI.

Results: A total of 1816 subjects (84.7%), including 686 men (37.8%) and 1130 women (62.2%), underwent ophthalmic examination in the mobile eye clinic. The mean (±standard deviation) age was 64.4 ± 9.6 years. The sensitivities, specificities, AUC, PLR, and NLR of RAAB were 90.3%, 99.3%, 0.948, 124.0, and 0.10, respectively, for detection of blindness (presenting visual acuity, PVA <3/60); 89.5%, 98.7%, 0.940, 69.2, and 0.11, respectively, for detection of economic blindness (PVA <6/60); and 90.3%, 97.7%, 0.940, 38.7, and 0.10, respectively, for detection of VI (PVA <6/18). The sensitivities, specificities, AUC, PLR, and NLR were 90.5%, 98.1%, 0.943, 48.1, and 0.10; and 60.4%, 98.7%, 0.796, 46.4, and 0.40 for detection of VI (PVA <6/18) owing to cataract and refractive error, respectively.

Conclusion: The diagnostic performances of RAAB were high for detecting the prevalence of blindness, VI, and VI owing to cataract.
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http://dx.doi.org/10.1016/j.ajo.2019.12.009DOI Listing
May 2020

Effects of combined rTMS and visual feedback on the rehabilitation of supernumerary phantom limbs in a patient with spinal cord injury: A case report.

World J Clin Cases 2019 Oct;7(19):3120-3125

Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

Background: Supernumerary phantom limb (SPL) caused by spinal cord injury (SCI) has previously been reported in several studies. However, the mechanisms and management of SPL in SCI patients are still not fully understood. Herein, we report a rare case of SPL in a patient with incomplete SCI.

Case Summary: A 46-year-old man complained of four hands 7 d after SCI. He was diagnosed with SPL complicated with actual limb neuropathic pain. Following a period of treatment with neurotrophic agents and Chinese traditional and analgesic medications, SPL symptoms and actual limb pain did not improve. However, his symptoms gradually lessened after combined treatment with high-frequency repetitive transcranial magnetic stimulation (rTMS), a promising neuromodulation technique, over the M1 cortex and visual feedback. After 7 wk of this treatment, SPL disappeared completely and actual limb pain was significantly relieved.

Conclusion: Cerebral plasticity changes may be a mechanism underlying the occurrence of non-painful SPL in SCI patients, and high-frequency rTMS applied to the M1 cortex could be a promising treatment method for SPL.
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http://dx.doi.org/10.12998/wjcc.v7.i19.3120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795722PMC
October 2019

Crosstalk between the Akt/mTORC1 and NF-κB signaling pathways promotes hypoxia-induced pulmonary hypertension by increasing DPP4 expression in PASMCs.

Acta Pharmacol Sin 2019 Oct 17;40(10):1322-1333. Epub 2019 Jul 17.

Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Abnormal wound healing by pulmonary artery smooth muscle cells (PASMCs) promotes vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Increasing evidence shows that both the mammalian target of rapamycin complex 1 (mTORC1) and nuclear factor-kappa B (NF-κB) are involved in the development of HPH. In this study, we explored the crosstalk between mTORC1 and NF-κB in PASMCs cultured under hypoxic condition and in a rat model of hypoxia-induced pulmonary hypertension (HPH). We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). In PASMCs, hypoxia activated mTORC1, which in turn promoted the phosphorylation of NF-κB. Molecular docking revealed that mTOR interacted with IκB kinases (IKKs) and that was validated by immunoprecipitation. In vitro kinase assays and mass spectrometry demonstrated that mTOR phosphorylated IKKα and IKKβ separately. Inhibition of mTORC1 decreased the level of phosphorylated IKKα/β, thus reducing the phosphorylation and transcriptional activity of NF-κB. Bioinformatics study revealed that dipeptidyl peptidase-4 (DPP4) was a target gene of NF-κB; DPP4 inhibitor, sitagliptin (10-500 μM) effectively inhibited the abnormal wound healing of PASMCs under hypoxic condition. In the rat model of HPH, we showed that NF-κB activation (at 3 weeks) was preceded by mTOR signaling activation (after 1 or 2 weeks) in lungs, and administration of sitagliptin (1-5 mg/kg every day, ig) produced preventive effects against the development of HPH. In conclusion, hypoxia activates the crosstalk between mTORC1 and NF-κB, and increased DPP4 expression in PASMCs that leads to vascular remodeling. Sitagliptin, a DPP4 inhibitor, exerts preventive effect against HPH.
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http://dx.doi.org/10.1038/s41401-019-0272-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786428PMC
October 2019

Ultrasound-targeted microbubble destruction improved the antiangiogenic effect of Endostar in triple-negative breast carcinoma xenografts.

J Cancer Res Clin Oncol 2019 May 25;145(5):1191-1200. Epub 2019 Feb 25.

Department of Ultrasound, Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.

Purpose: Ultrasound-targeted microbubble destruction (UTMD) has been reported to be a meritorious technique for drug targeting delivery. In this study, we aimed to evaluate the synergistic antiangiogenic effect of UTMD combined with Endostar on triple-negative breast carcinoma tumors.

Materials And Methods: The lipid-shelled microbubbles (MBs) conjugated with Endostar were constructed using a biotin-avidin bridging chemistry method, and the morphological characteristics and drug-conjugating content were determined. MBs were administered intravenously to nude mice bearing MDA-MB-231 breast carcinoma xenografts and ultrasound exposure followed. The tumor microcirculation was observed by contrast-enhanced ultrasonography (CEUS) and the Endostar biodistribution was detected by enzyme-linked immunosorbent assay. Twenty-four breast carcinoma-bearing nude mice were divided into four groups. After treatment, every 3 days for 15 days the in vivo antitumor effects were assessed by calculating the tumor growth inhibition rate (TGIR). The tumor microcirculation was observed by CEUS, the tumor microvessel density (MVD) was calculated by immunohistochemistry under a microscope, and the vascular endothelial growth factor (VEGF) gene expression was detected by real-time quantitative polymerase chain reaction.

Results: The prepared Endostar-conjugated MBs were round and well-dispersed with a mean size of 2.8 ± 0.7 µm and a drug conjugating content of 800.72 ± 70.53 µg/10 MBs. UTMD blocked the tumor microcirculation, and improved Endostar release in the targeted tumor tissue with a drug content of 1.12 ± 0.43 µg/gram protein, which was about three times higher than that in Endostar group or Endostar conjugated MBs group. Endostar-conjugated MBs combined with UTMD treatment achieved the optimal antitumor effects in vivo with a TGIR of 46.29%, and apparent antiangiogenic effects with minimal tumor blood perfusion, MVD and VEGF gene expression level.

Conclusion: UTMD can improve Endostar delivery in the targeting tumor tissue and mediate synergistic antiangiogenetic and antitumor effects, which may be a potential therapeutic strategy for refractory breast cancer.
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http://dx.doi.org/10.1007/s00432-019-02866-7DOI Listing
May 2019

SMRT sequencing of the full-length transcriptome of the Sunda pangolin (Manis javanica).

Gene 2019 Apr 19;692:208-216. Epub 2019 Jan 19.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong, China. Electronic address:

It is widely known that transcriptional diversity contributes greatly to biological regulation in eukaryotes. With the development of next-generation sequencing (NGS) technologies, several studies on RNA sequencing have considerably improved our understanding of transcriptome complexity. However, obtaining full-length (FL) transcripts remains a considerable challenge because of difficulties in short read-based assembly. In the present study, single-molecule real-time (SMRT) sequencing and NGS were combined to generate the complete and FL transcriptome of Manis javanica. The results provide a comprehensive set of reference transcripts and hence contribute to the improved annotation of the M. javanica genome. We obtained 45,530 high-confidence transcripts from 19,109 genic loci, of which 8014 genes have not yet been annotated within the M. javanica genome. Furthermore, we revealed 8824 long-chain noncoding RNAs (lncRNAs). A total of 30,199 alternative splicing (AS) and 11,184 alternative polyadenylation (APA) events were identified in the sequencing data. The structure and expression level of 59 digestive enzyme genes, including 13 carbohydrase genes, 28 lipase genes and 18 protease genes, were analyzed, which might provide original data for further research on M. javanica.
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http://dx.doi.org/10.1016/j.gene.2019.01.008DOI Listing
April 2019

The Fecal Metagenomics of Malayan Pangolins Identifies an Extensive Adaptation to Myrmecophagy.

Front Microbiol 2018 23;9:2793. Epub 2018 Nov 23.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, China.

The characteristics of flora in the intestine of an animal, including the number and abundance of different microbial species and their functions, are closely related to the diets of the animal and affect the physical condition of the host. The Malayan pangolin () is an endangered species that specializes in myrmecophagy. Analyzing the microbiome in the intestine of the pangolin is imperative to protect this species. By sequencing the metagenomes of the feces of four pangolins, we constructed a non-redundant catalog of 211,868 genes representing 1,811 metagenomic species. Taxonomic annotation revealed that Bacteroidetes (49.9%), Proteobacteria (32.2%), and Firmicutes (12.6%) are the three main phyla. The annotation of gene functions identified 5,044 genes from 88 different glycoside hydrolase (GH) families in the Carbohydrate-Active enZYmes database and 114 gene modules related to chitin-degrading enzymes, corresponding to the catalytic domains of GH18 family enzymes, containing chitinase genes of classes III and V in the dataset. Fourteen gene modules corresponded to the catalytic domains of GH19 family enzymes, containing chitinase genes of classes I, II, and IV. These genes were found in 37 species belonging to four phyla: Bacteroidetes, Cyanobacteria, Firmicutes, and Proteobacteria. Moreover, when the metabolic pathways of these genes were summarized, 41,711 genes were associated with 147 unique KEGG metabolic pathways, and these genes were assigned to two Gene Ontology terms: metabolic process and catalytic activity. We also found several species that likely play roles in the digestion of cellulose and may be able to degrade chitin, including , and . In addition, we identified some intestinal microflora and genes related to diseases in pangolins. Twenty-seven species were identified by STAMP analysis as differentially abundant in healthy and diseased animals: 20 species, including and , were more abundant in healthy pangolins, while seven species, including , and , were more abundant in diseased pangolins. These results will support the efforts to conserve pangolins.
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http://dx.doi.org/10.3389/fmicb.2018.02793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265309PMC
November 2018

Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors.

Bioorg Med Chem 2019 01 7;27(1):65-78. Epub 2018 Nov 7.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. The most potent compound 10a forms better interaction with Aurora A than Aurora B in molecular docking. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors.
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http://dx.doi.org/10.1016/j.bmc.2018.11.006DOI Listing
January 2019

Acidic mammalian chitinase gene is highly expressed in the special oxyntic glands of .

FEBS Open Bio 2018 Aug 4;8(8):1247-1255. Epub 2018 Jul 4.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization Guangdong Public Laboratory of Wild Animal Conservation and Utilization Guangdong Institute of Applied Biological Resources Guangzhou China.

The Malayan pangolin () is a mammal that feeds primarily on ants and termites, which contain the energy-rich carbohydrate chitin. Chitin is digestible by endogenous enzymes of the typical mammalian gastrointestinal tract, especially the acidic mammalian chitinase (AMCase). The objective of this research was to determine whether AMCase activity is expressed in the stomach of . The stomach tissues were divided into three parts: the gastric sack, the oxyntic glands, and the pyloric musculature, which were assayed by conventional RT-PCR, quantitative reverse transcriptase-coupled PCR (qPCR) and western blot. Information regarding 3D structural models of AMCase was also obtained. In conclusion, acidic mammalian chitinase is highly expressed in the oxyntic glands of the species.
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http://dx.doi.org/10.1002/2211-5463.12461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070644PMC
August 2018

A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and Enhanced Protective Immune Response.

Viruses 2018 01 15;10(1). Epub 2018 Jan 15.

College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing 100044, China.

Human respiratory syncytial virus (RSV) is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified vaccines, especially with the higher 20 copies, resulted in an enhanced shift toward a Th1-biased antibody and T-cell response, a decrease in pulmonary pathology and virus replication, and a decrease in weight loss after RSV challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of improving the efficacy of DNA vaccine against RSV infection.
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http://dx.doi.org/10.3390/v10010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795451PMC
January 2018

Transcriptomic analysis identifies genes and pathways related to myrmecophagy in the Malayan pangolin ().

PeerJ 2017 22;5:e4140. Epub 2017 Dec 22.

Guangdong Key Laboratory of Animal Conservation and Resource, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong, China.

The Malayan pangolin () is an unusual, scale-covered, toothless mammal that specializes in myrmecophagy. Due to their threatened status and continuing decline in the wild, concerted efforts have been made to conserve and rescue this species in captivity in China. Maintaining this species in captivity is a significant challenge, partly because little is known of the molecular mechanisms of its digestive system. Here, the first large-scale sequencing analyses of the salivary gland, liver and small intestine transcriptomes of an adult genome were performed, and the results were compared with published liver transcriptome profiles for a pregnant female. A total of 24,452 transcripts were obtained, among which 22,538 were annotated on the basis of seven databases. In addition, 3,373 new genes were predicted, of which 1,459 were annotated. Several pathways were found to be involved in myrmecophagy, including olfactory transduction, amino sugar and nucleotide sugar metabolism, lipid metabolism, and terpenoid and polyketide metabolism pathways. Many of the annotated transcripts were involved in digestive functions: 997 transcripts were related to sensory perception, 129 were related to digestive enzyme gene families, and 199 were related to molecular transporters. One transcript for an acidic mammalian chitinase was found in the annotated data, and this might be closely related to the unique digestive function of pangolins. These pathways and transcripts are involved in specialization processes related to myrmecophagy (a form of insectivory) and carbohydrate, protein and lipid digestive pathways, probably reflecting adaptations to myrmecophagy. Our study is the first to investigate the molecular mechanisms underlying myrmecophagy in and we hope that our results may play a role in the conservation of this species.
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http://dx.doi.org/10.7717/peerj.4140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742527PMC
December 2017

Diets Alter the Gut Microbiome of Crocodile Lizards.

Front Microbiol 2017 25;8:2073. Epub 2017 Oct 25.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, China.

The crocodile lizard is a critically endangered reptile, and serious diseases have been found in this species in recent years, especially in captive lizards. Whether these diseases are caused by changes in the gut microbiota and the effect of captivity on disease remains to be determined. Here, we examined the relationship between the gut microbiota and diet and disease by comparing the fecal microbiota of wild lizards with those of sick and healthy lizards in captivity. The gut microbiota in wild crocodile lizards was consistently dominated by Proteobacteria (∼56.4%) and Bacteroidetes (∼19.1%). However, the abundance of Firmicutes (∼2.6%) in the intestine of the wild crocodile lizards was distinctly lower than that in other vertebrates. In addition, the wild samples from Guangdong Luokeng National Nature Reserve also had a high abundance of Deinococcus-Thermus while the wild samples from Guangxi Daguishan Crocodile Lizard National Nature Reserve had a high abundance of Tenericutes. The gut microbial community in loach-fed crocodile lizards was significantly different from the gut microbial community in the earthworm-fed and wild lizards. In addition, significant differences in specific bacteria were detected among groups. Notably, in the gut microbiota, the captive lizards fed earthworms resulted in enrichment of , and the captive lizards fed loaches had higher abundances of , and , all of which are pathogens or opportunistic pathogens in human or other animals. However, there is no sufficient evidence that the gut microbiota contributes to either disease A or disease B. These results provide a reference for the conservation of endangered crocodile lizards and the first insight into the relationship between disease and the gut microbiota in lizards.
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http://dx.doi.org/10.3389/fmicb.2017.02073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660983PMC
October 2017

Estradiol Regulates Txnip and Prevents Intermittent Hypoxia-Induced Vascular Injury.

Sci Rep 2017 09 4;7(1):10318. Epub 2017 Sep 4.

Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.

Chronic intermittent hypoxia (IH) contributes to obstructive sleep apnea (OSA)-related cardiovascular diseases through increasing oxidative stress. It has been widely recognized that estradiol decreases the risk for cardiovascular disease, but the estrogen replacement therapy is limited for its side effects. Thioredoxin (Trx) and its endogenous inhibitor, thioredoxin-interacting protein (Txnip), are associated with the protective effect of estradiol in some conditions. In this study, we aimed to explore whether estradiol could protect against IH-induced vascular injury, and the possible effect of Trx-1/Txnip in this process. Forty-eight adult female C57/BL6J mice were randomly divided into 4 groups, ovariectomy combined with IH group, sham operation combined with IH group, IH group and the control group. The mice treated with IH for 8 hrs/day, and 28 days. IH induced the injury of aorta, and ovariectomized mice were more prone to the IH-induced aortic injury, with higher level of oxidative stress. In vitro, estradiol increased Trx-1 level, but decreased the level of Txnip and oxidative stress in human umbilical vein endothelial cells (HUVECs) treated with IH for 16 hrs. Knock-down of Txnip by specific siRNA rescued oxidative stress and apoptosis. In conclusion, estradiol protects against IH-induced vascular injury, partially through the regulation of Trx-1/Txnip pathway.
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http://dx.doi.org/10.1038/s41598-017-10442-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583380PMC
September 2017

A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

Antiviral Res 2017 08 18;144:57-69. Epub 2017 May 18.

College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. Electronic address:

Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production.
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http://dx.doi.org/10.1016/j.antiviral.2017.05.005DOI Listing
August 2017

Enhanced humoral and CD8+ T cell immunity in mice vaccinated by DNA vaccine against human respiratory syncytial virus through targeting the encoded F protein to dendritic cells.

Int Immunopharmacol 2017 May 1;46:62-69. Epub 2017 Mar 1.

College of Life Sciences & Bioengineering, Beijing Jiaotong University, 3 Shangyuan Cun, Haidian District, Beijing 100044, China. Electronic address:

Human respiratory syncytial virus (RSV) is the most important cause of serious lower respiratory tract infection in infants, the elderly, and the immunocompromised population. There is no licensed vaccine against RSV until now. It has been reported that targeting antigen to DEC205, a phagocytosis receptor on dendritic cells (DCs), could induce enhanced CD4+ and CD8+ T cell responses in mice. To develop RSV DNA vaccine and target the encoded antigen protein to DCs, the ectodomain of fusion glycoprotein (sF, amino acids: 23-524) of RSV was fused with anti-DEC205 single-chain Fv fragment (scDEC) and designated scDECF. Following successful expression from the recombinant plasmid of pVAX1/scDECF, the recombinant protein of scDECF was found capable of specifically binding to DEC205 receptor on CHOmDEC205 cells, and facilitating uptake of RSV F by DC2.4 cells in vitro. Furthermore, the higher levels of RSV-specific IgG antibody responses and neutralization antibody titers, as well as RSV F-specific CD8+ T cell responses were induced in mice immunized intramuscularly by pVAX1/scDECF than by the control plasmid of pVAX1/scISOF encoding sF protein fused with isotype matched control single-chain Fv fragment (scISO). Compared with pVAX1/scISOF, both the ratio of IgG2a/IgG1, >1, and the enhanced IFN-γ cytokine were induced in mice following pVAX1/scDECF immunization, which exhibited a Th1 dominant response in pVAX1/scDECF vaccinated mice. Notably, the elevated efficiency of RSV F protein bound by DCs in vivo could also be observed in mice inoculated by pVAX1/scDECF. Collectively, these results demonstrate the enhanced IgG and CD8 T cell immune responses have been induced successfully by DNA vaccine against RSV by targeting F antigen to DCs via the DEC205 receptor, and this DC-targeting vaccine strategy merits further investigation.
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http://dx.doi.org/10.1016/j.intimp.2017.02.023DOI Listing
May 2017

[Study of Modeling Samples Selection Method Based on Near Infrared Spectrum].

Guang Pu Xue Yu Guang Pu Fen Xi 2016 Dec;36(12):3920-5

For more wheat varieties classification problem, we use near infrared spectrumto do qualitative analysis. Increasing the size of modeling sample could increase information of the model, however, at the same time, it also makes information redundancy so that modeling time and storage space will increase, thus, we need to decrease the size of modeling sample though selecting them. Some information must be lost and the effects of the model must be worse if we select samples blindly. We put forward the k nearest neighbor-density sample selection based on the traditional selection methods. Experiments use the near infrared diffuse reflection spectrum of wheat seed from lots of days. First, we use preprocessing and feature extraction to deal with the wheat original spectrum, then select modeling sample by three methods that are random sampling, k nearest neighbor and k nearest neighbor-density, finally, we establish the models of BPR(Biomimetic Pattern Recognition) and BPRI(Biomimetic Pattern Recognition Improved). The experimental results show that in the model of BPR we get the best results using the selection method of k nearest neighbor-density, especially it also decreases the size of modeling sample deeply, and in the model of BPRI the results using the selection method of k nearest neighbor-density are much better than random sampling and a little better than k nearest neighbor, but in the meanwhile the size of modeling sample using the selection method of k nearest neighbor-density are much smaller than k nearest neighbor. The experimental results prove that the sample selection method of k nearest neighbor-density can not only greatly reduce the modeling sample size, and ensure the quality of the model, it has obvious effect on varieties classification problem of wheat.
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December 2016

Construction of protein interaction network involved in lung adenocarcinomas using a novel algorithm.

Oncol Lett 2016 Sep 7;12(3):1792-1800. Epub 2016 Jul 7.

Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.

Studies that only assess differentially-expressed (DE) genes do not contain the information required to investigate the mechanisms of diseases. A complete knowledge of all the direct and indirect interactions between proteins may act as a significant benchmark in the process of forming a comprehensive description of cellular mechanisms and functions. The results of protein interaction network studies are often inconsistent and are based on various methods. In the present study, a combined network was constructed using selected gene pairs, following the conversion and combination of the scores of gene pairs that were obtained across multiple approaches by a novel algorithm. Samples from patients with and without lung adenocarcinoma were compared, and the RankProd package was used to identify DE genes. The empirical Bayesian (EB) meta-analysis approach, the search tool for the retrieval of interacting genes/proteins database (STRING), the weighted gene coexpression network analysis (WGCNA) package and the differentially-coexpressed genes and links package (DCGL) were used for network construction. A combined network was also constructed with a novel rank-based algorithm using a combined score. The topological features of the 5 networks were analyzed and compared. A total of 941 DE genes were screened. The topological analysis indicated that the gene interaction network constructed using the WGCNA method was more likely to produce a small-world property, which has a small average shortest path length and a large clustering coefficient, whereas the combined network was confirmed to be a scale-free network. Gene pairs that were identified using the novel combined method were mostly enriched in the cell cycle and p53 signaling pathway. The present study provided a novel perspective to the network-based analysis. Each method has advantages and disadvantages. Compared with single methods, the combined algorithm used in the present study may provide a novel method to analyze gene interactions, with increased credibility.
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http://dx.doi.org/10.3892/ol.2016.4822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998145PMC
September 2016

Protective effects of phillyrin against influenza A virus in vivo.

Arch Pharm Res 2016 Jul 21;39(7):998-1005. Epub 2016 Jun 21.

Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, 100850, Beijing, People's Republic of China.

Influenza A virus infection represents a great threat to public health. However, owing to side effects and the emergence of resistant virus strains, the use of currently available anti-influenza drugs may be limited. In order to identify novel anti-influenza drugs, we investigated the antiviral effects of phillyrin against influenza A virus infection in vivo. The mean survival time, lung index, viral titers, influenza hemagglutinin (HA) protein and serum cytokines levels, and histopathological changes in lung tissue were examined. Administration of phillyrin at a dose of 20 mg/kg/day for 3 days significantly prolonged the mean survival time, reduced the lung index, decreased the virus titers and interleukin-6 levels, reduced the expression of HA, and attenuated lung tissue damage in mice infected with influenza A virus. Taken together, these data showed that phillyrin had potential protective effects against infection caused by influenza A virus.
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http://dx.doi.org/10.1007/s12272-016-0775-zDOI Listing
July 2016