Publications by authors named "Ruilin Li"

32 Publications

iTRAQ-based quantitative proteomic analysis of silkworm infected with Beauveria bassiana.

Mol Immunol 2021 Apr 28;135:204-216. Epub 2021 Apr 28.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, 212018, China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, 212018, China. Electronic address:

Beauveria bassiana is a harmful pathogen to the economically important insect silkworm, always causes serious disease to the silkworm, which results in great losses to the sericulture industry. In order to explore the silkworm (Bombyx mori) response to B. bassiana infection, differential proteomes of the silkworm responsive to B. bassiana infection were identified with isobaric tags for relative and absolute quantitation (iTRAQ) at the different stage of the 3rd instar silkworm larvae. Among the 5040 proteins identified with confidence level of ≥95 %, total 937 proteins were differentially expressed, of which 488 proteins were up-regulated and 449 proteins were down-regulated. 23, 15, 250, 649 differentially expressed proteins (DEPs) were reliably quantified by iTRAQ analysis in the B. bassiana infected larvae at 18, 24, 36, 48 h post infection (hpi) respectively. Based on GO annotations, 6, 4, 128, 316 DEPs were involved in biological processes, 12, 5, 143, 376 DEPs were involved in molecular functions, and 6, 3, 108, 256 DEPs were involved in cell components at 18, 24, 36, 48 hpi respectively. KEGG pathway analysis displayed that 18, 12, 210, 548 DEPs separately participated in 63, 35, 201, 264 signal transduction pathways at different time of infection, and moreover a higher proportion of DEPs involved in metabolic pathways. The cluster analysis on the DEPs of different infection stages distinguished a co-regulated DEP, lysozyme precursor, which was up-regulated at both the mRNA level and the protein level, indicating that the lysozyme protein kept playing an important role in defending the silkworm against B. bassiana infection. This was the first report using an iTRAQ approach to analyze proteomes of the whole silkworm against B. bassiana infection, which contributes to better understanding the defense mechanisms of silkworm to B. bassiana infection and provides important experimental data for the identification of key factors involved in the interaction between the pathogenic fungus and its host.
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http://dx.doi.org/10.1016/j.molimm.2021.04.018DOI Listing
April 2021

A compact and interpretable convolutional neural network for cross-subject driver drowsiness detection from single-channel EEG.

Methods 2021 Apr 24. Epub 2021 Apr 24.

Fraunhofer Singapore, Nanyang Technological University, Singapore. Electronic address:

Driver drowsiness is one of the main factors leading to road fatalities and hazards in the transportation industry. Electroencephalography (EEG) has been considered as one of the best physiological signals to detect drivers' drowsy states, since it directly measures neurophysiological activities in the brain. However, designing a calibration-free system for driver drowsiness detection with EEG is still a challenging task, as EEG suffers from serious mental and physical drifts across different subjects. In this paper, we propose a compact and interpretable Convolutional Neural Network (CNN) to discover shared EEG features across different subjects for driver drowsiness detection. We incorporate the Global Average Pooling (GAP) layer in the model structure, allowing the Class Activation Map (CAM) method to be used for localizing regions of the input signal that contribute most for classification. Results show that the proposed model can achieve an average accuracy of 73.22% on 11 subjects for 2-class cross-subject EEG signal classification, which is higher than conventional machine learning methods and other state-of-art deep learning methods. It is revealed by the visualization technique that the model has learned biologically explainable features, e.g., Alpha spindles and Theta burst, as evidence for the drowsy state. It is also interesting to see that the model uses artifacts that usually dominate the wakeful EEG, e.g., muscle artifacts and sensor drifts, to recognize the alert state. The proposed model illustrates a potential direction to use CNN models as a powerful tool to discover shared features related to different mental states across different subjects from EEG signals.
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http://dx.doi.org/10.1016/j.ymeth.2021.04.017DOI Listing
April 2021

Comprehensive review and evaluation of computational methods for identifying FLT3-internal tandem duplication in acute myeloid leukaemia.

Brief Bioinform 2021 Apr 13. Epub 2021 Apr 13.

Computer Network Information Center, Chinese Academy of Sciences. His research interests include cancer genomics, metagenomics, and the development of computational tools for working with data from next-generation sequencing technologies. His affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.

Internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3-ITD) constitutes an independent indicator of poor prognosis in acute myeloid leukaemia (AML). AML with FLT3-ITD usually presents with poor treatment outcomes, high recurrence rate and short overall survival. Currently, polymerase chain reaction and capillary electrophoresis are widely adopted for the clinical detection of FLT3-ITD, whereas the length and mutation frequency of ITD are evaluated using fragment analysis. With the development of sequencing technology and the high incidence of FLT3-ITD mutations, a multitude of bioinformatics tools and pipelines have been developed to detect FLT3-ITD using next-generation sequencing data. However, systematic comparison and evaluation of the methods or software have not been performed. In this study, we provided a comprehensive review of the principles, functionality and limitations of the existing methods for detecting FLT3-ITD. We further compared the qualitative and quantitative detection capabilities of six representative tools using simulated and biological data. Our results will provide practical guidance for researchers and clinicians to select the appropriate FLT3-ITD detection tools and highlight the direction of future developments in this field. Availability: A Docker image with several programs pre-installed is available at https://github.com/niu-lab/docker-flt3-itd to facilitate the application of FLT3-ITD detection tools.
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http://dx.doi.org/10.1093/bib/bbab099DOI Listing
April 2021

Subject matching for cross-subject EEG-based recognition of driver states related to situation awareness.

Methods 2021 Apr 22. Epub 2021 Apr 22.

Fraunhofer Singapore, Singapore 639798, Singapore. Electronic address:

Situation awareness (SA) has received much attention in recent years because of its importance for operators of dynamic systems. Electroencephalography (EEG) can be used to measure mental states of operators related to SA. However, cross-subject EEG-based SA recognition is a critical challenge, as data distributions of different subjects vary significantly. Subject variability is considered as a domain shift problem. Several attempts have been made to find domain-invariant features among subjects, where subject-specific information is neglected. In this work, we propose a simple but efficient subject matching framework by finding a connection between a target (test) subject and source (training) subjects. Specifically, the framework includes two stages: (1) we train the model with multi-source domain alignment layers to collect source domain statistics. (2) During testing, a distance is computed to perform subject matching in the latent representation space. We use a reciprocal exponential function as a similarity measure to dynamically select similar source subjects. Experiment results show that our framework achieves a state-of-the-art accuracy 74.32% for the Taiwan driving dataset.
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http://dx.doi.org/10.1016/j.ymeth.2021.04.009DOI Listing
April 2021

The structural characteristic of acidic-hydrolyzed corn silk polysaccharides and its protection on the HO-injured intestinal epithelial cells.

Food Chem 2021 Mar 26;356:129691. Epub 2021 Mar 26.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China. Electronic address:

This work aims to describe the purification and characterization of acidic-hydrolyzed corn silk polysaccharides (AH-CSP) and evaluate their protection on the HO-injured intestinalepithelial cells (IEC-6). Two fractions named AHP-1 and AHP-2 were obtained from AH-CSP, and physicochemical properties of them were investigated by gel permeation chromatography (GPC), gas chromatography (GC), nuclear magnetic resonance (NMR), fourier transform infrared (FT-IR) spectroscopy, scanning electronic microscopy (SEM), and Congo red test. Results showed that AHP-1 (2.80 × 10 Da) and AHP-2 (1.25 × 10 Da) were consisted of xylose, mannose, galactose, rhamnose, arabinose, and glucose. AHP-1 and AHP-2 had strong scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-Azobis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), and OH· free radicals. Furthermore, pretreatment with AHP-2 could protect the HO-injured IEC-6 cells by effectively scavenging the overproduced reactive oxygen species (ROS) and regulating of Kelch-like ECH-associated protein 1(Keap1)/ nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway.
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http://dx.doi.org/10.1016/j.foodchem.2021.129691DOI Listing
March 2021

Survival Analysis on Rare Events Using Group-Regularized Multi-Response Cox Regression.

Bioinformatics 2021 Feb 9. Epub 2021 Feb 9.

Department of Biomedical Data Science, Stanford University, Stanford, United States.

Motivation: The prediction performance of Cox proportional hazard model suffers when there are only few uncensored events in the training data.

Results: We propose a Sparse-Group regularized Cox regression method to improve the prediction performance of large-scale and high-dimensional survival data with few observed events. Our approach is applicable when there is one or more other survival responses that 1. has a large number of observed events; 2. share a common set of associated predictors with the rare event response. This scenario is common in the UK Biobank (Sudlow et al., 2015) dataset where records for a large number of common and less prevalent diseases of the same set of individuals are available. By analyzing these responses together, we hope to achieve higher prediction performance than when they are analyzed individually. To make this approach practical for large-scale data, we developed an accelerated proximal gradient optimization algorithm as well as a screening procedure inspired by Qian et al. (2020).

Availability: https://github.com/rivas-lab/multisnpnet-Cox.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab095DOI Listing
February 2021

MSIsensor-ct: microsatellite instability detection using cfDNA sequencing data.

Brief Bioinform 2021 Jan 18. Epub 2021 Jan 18.

Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China.

Motivation: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach.

Results: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines.

Availability: MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct.

Supplementary Information: Supplementary data are available at Briefings in Bioinformatics online.
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http://dx.doi.org/10.1093/bib/bbaa402DOI Listing
January 2021

A multifunctional CeO@SiO-PEG nanoparticle carrier for delivery of food derived proanthocyanidin and curcumin as effective antioxidant, neuroprotective and anticancer agent.

Food Res Int 2020 11 17;137:109674. Epub 2020 Sep 17.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China. Electronic address:

The nanoparticle systems could effectively overcome the drug delivery challenges of food bioactive compounds. In this study, a novel and effective multifunctional PEG modified CeO@SiO nanoparticle (CSP-NPs) system was successfully fabricated. Food derived proanthocyanidin (PAC) and curcumin (Cur) were loaded onto CSP-NPs and formed as PAC-NPs and Cur-NPs. Fourier transform Infrared spectra, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and dynamic light scattering were used to characterize the prepared NPs. CSP-NPs, PAC-NPs and Cur-NPs displayed spherical shape with about 35-45 nm size. The bioactivity analysis revealed that CSP-NPs system could effectively deliver PAC and Cur to exhibit strong antioxidant activity, potent neuroprotective effect against Aβ-mediated toxicity in PC-12 cells (recovered cell viability from 57.5% to 81.0% at the dose of 25 μg/mL) and effective antiproliferative effects on HepG2 and Hela cells. Besides, all prepared nanoparticles (0-100 µg/ml) used in this study showed no significant toxicity on cell models of antioxidative and neuroprotective activities, excepting for cancer cells, suggesting that these nanoparticles had the potential of being utilized in drug delivery. Therefore, CSP-NPs might be a promising delivery system for hydrophilic molecule proanthocyanidin and hydrophobic molecule curcumin against the oxidative damage, neurodegenerative diseases and cancer, which could facilitate the application of food derived nutrients in functional foods industry.
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http://dx.doi.org/10.1016/j.foodres.2020.109674DOI Listing
November 2020

Chemical structure and inhibition on α-glucosidase of polysaccharides from corn silk by fractional precipitation.

Carbohydr Polym 2021 Jan 2;252:117185. Epub 2020 Oct 2.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, PR China. Electronic address:

Aimed to explore different corn silk polysaccharide (CSP) fractions derived by ethanol precipitation on the physicochemical properties and biological activities, four fractions (CSP20, CSP40, CSP60, and CSP80) were obtained. CSPs consisted of mannose, galactose, arabinose, rhamnose, xylose, and glucose with different ratios, and exhibited different total sugar content, uronic acid content, protein content, and total phenols content. All fractions also showed different physical properties, such as molecular weight, intrinsic viscosity, particle size, and microstructure. Besides, CSP80 exhibited stronger antioxidant activity and α-glucosidase inhibitory activity than the other three fractions. Enzyme kinetic analysis suggested that CSP80 inhibited α-glucosidase by mixed type and reversible mechanisms, respectively. Fluorescence intensity measurements confirmed that the secondary structure of α-glucosidase was changed by the binding of CSP80. Isothermal titration calorimetry (ITC) results illustrated that the binding of CSP80 to α-glucosidase complex was spontaneous driven by enthalpy and hydrogen bonds played a major role in the binding.
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http://dx.doi.org/10.1016/j.carbpol.2020.117185DOI Listing
January 2021

Fast Lasso method for large-scale and ultrahigh-dimensional Cox model with applications to UK Biobank.

Biostatistics 2020 Sep 29. Epub 2020 Sep 29.

Department of Statistics and Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.

We develop a scalable and highly efficient algorithm to fit a Cox proportional hazard model by maximizing the $L^1$-regularized (Lasso) partial likelihood function, based on the Batch Screening Iterative Lasso (BASIL) method developed in Qian and others (2019). Our algorithm is particularly suitable for large-scale and high-dimensional data that do not fit in the memory. The output of our algorithm is the full Lasso path, the parameter estimates at all predefined regularization parameters, as well as their validation accuracy measured using the concordance index (C-index) or the validation deviance. To demonstrate the effectiveness of our algorithm, we analyze a large genotype-survival time dataset across 306 disease outcomes from the UK Biobank (Sudlow and others, 2015). We provide a publicly available implementation of the proposed approach for genetics data on top of the PLINK2 package and name it snpnet-Cox.
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http://dx.doi.org/10.1093/biostatistics/kxaa038DOI Listing
September 2020

Anxiety and related factors in frontline clinical nurses fighting COVID-19 in Wuhan.

Medicine (Baltimore) 2020 Jul;99(30):e21413

Department of Urology, The Third People's Hospital of Hubei Province, Wuhan, China.

The aim of this study was to examine the anxiety status of the frontline clinical nurses in the designated hospitals for the treatment of coronavirus disease 2019 (COVID-19) in Wuhan and to analyze the influencing factors, to provide data for psychologic nursing.This study used a cross-sectional survey design and convenience sampling. The questionnaires were completed by 176 frontline clinical nurses. Anxiety was determined using the Hamilton anxiety scale. General data were collected using a survey. Correlation analyses were used.Among the 176 frontline nurses, 77.3% (136/176) had anxiety. The anxiety scores of the frontline clinical nurse fighting COVID-19 were 17.1 ± 8.1. Anxiety symptoms, mild to moderate anxiety symptoms, and severe anxiety symptoms were found in 27.3%, 25%, and 25% of the nurses, respectively. Sex, age, marital status, length of service, and clinical working time against COVID-19 were associated with anxiety (P < .05).The frontline nurses working in the designated hospitals for the treatment of COVID-19 in Wuhan had serious anxiety. Sex, age, length of service, and clinical working time against COVID-19 were associated with anxiety in those nurses. Psychologic care guidance, counseling, and social support should be provided to the nurses to reduce their physical and mental burden. Nursing human resources in each province should be adjusted according to each province's reality.
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http://dx.doi.org/10.1097/MD.0000000000021413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387028PMC
July 2020

Comprehensive fundamental somatic variant calling and quality management strategies for human cancer genomes.

Brief Bioinform 2020 Jun 8. Epub 2020 Jun 8.

Next-generation sequencing (NGS) technology has revolutionised human cancer research, particularly via detection of genomic variants with its ultra-high-throughput sequencing and increasing affordability. However, the inundation of rich cancer genomics data has resulted in significant challenges in its exploration and translation into biological insights. One of the difficulties in cancer genome sequencing is software selection. Currently, multiple tools are widely used to process NGS data in four stages: raw sequence data pre-processing and quality control (QC), sequence alignment, variant calling and annotation and visualisation. However, the differences between these NGS tools, including their installation, merits, drawbacks and application, have not been fully appreciated. Therefore, a systematic review of the functionality and performance of NGS tools is required to provide cancer researchers with guidance on software and strategy selection. Another challenge is the multidimensional QC of sequencing data because QC can not only report varied sequence data characteristics but also reveal deviations in diverse features and is essential for a meaningful and successful study. However, monitoring of QC metrics in specific steps including alignment and variant calling is neglected in certain pipelines such as the 'Best Practices Workflows' in GATK. In this review, we investigated the most widely used software for the fundamental analysis and QC of cancer genome sequencing data and provided instructions for selecting the most appropriate software and pipelines to ensure precise and efficient conclusions. We further discussed the prospects and new research directions for cancer genomics.
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http://dx.doi.org/10.1093/bib/bbaa083DOI Listing
June 2020

HotSpot3D web server: an integrated resource for mutation analysis in protein 3D structures.

Bioinformatics 2020 06;36(12):3944-3946

Computer Network Information Center, Chinese Academy of Sciences.

Motivation: HotSpot3D is a widely used software for identifying mutation hotspots on the 3D structures of proteins. To further assist users, we developed a new HotSpot3D web server to make this software more versatile, convenient and interactive.

Results: The HotSpot3D web server performs data pre-processing, clustering, visualization and log-viewing on one stop. Users can interactively explore each cluster and easily re-visualize the mutational clusters within browsers. We also provide a database that allows users to search and visualize proximal mutations from 33 cancers in the Cancer Genome Atlas.

Availability And Implementation: http://niulab.scgrid.cn/HotSpot3D/.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa258DOI Listing
June 2020

Gclust: A Parallel Clustering Tool for Microbial Genomic Data.

Genomics Proteomics Bioinformatics 2019 10 7;17(5):496-502. Epub 2020 Jan 7.

Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100190, China; Guizhou University School of Medicine, Guiyang 550025, China. Electronic address:

The accelerating growth of the public microbial genomic data imposes substantial burden on the research community that uses such resources. Building databases for non-redundant reference sequences from massive microbial genomic data based on clustering analysis is essential. However, existing clustering algorithms perform poorly on long genomic sequences. In this article, we present Gclust, a parallel program for clustering complete or draft genomic sequences, where clustering is accelerated with a novel parallelization strategy and a fast sequence comparison algorithm using sparse suffix arrays (SSAs). Moreover, genome identity measures between two sequences are calculated based on their maximal exact matches (MEMs). In this paper, we demonstrate the high speed and clustering quality of Gclust by examining four genome sequence datasets. Gclust is freely available for non-commercial use at https://github.com/niu-lab/gclust. We also introduce a web server for clustering user-uploaded genomes at http://niulab.scgrid.cn/gclust.
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http://dx.doi.org/10.1016/j.gpb.2018.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056916PMC
October 2019

How Big Data and High-performance Computing Drive Brain Science.

Genomics Proteomics Bioinformatics 2019 08 2;17(4):381-392. Epub 2019 Dec 2.

Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100190, China; Guizhou University School of Medicine, Guiyang 550025, China. Electronic address:

Brain science accelerates the study of intelligence and behavior, contributes fundamental insights into human cognition, and offers prospective treatments for brain disease. Faced with the challenges posed by imaging technologies and deep learning computational models, big data and high-performance computing (HPC) play essential roles in studying brain function, brain diseases, and large-scale brain models or connectomes. We review the driving forces behind big data and HPC methods applied to brain science, including deep learning, powerful data analysis capabilities, and computational performance solutions, each of which can be used to improve diagnostic accuracy and research output. This work reinforces predictions that big data and HPC will continue to improve brain science by making ultrahigh-performance analysis possible, by improving data standardization and sharing, and by providing new neuromorphic insights.
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http://dx.doi.org/10.1016/j.gpb.2019.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943776PMC
August 2019

Expressional analysis of the silkworm storage protein 1 and identification of its interacting proteins.

Insect Mol Biol 2020 02 30;29(1):66-76. Epub 2019 Jul 30.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, China.

Storage proteins are haemolymph-specific proteins in insects, mainly synthesized in the fat body, released into the haemolymph, and then selectively reabsorbed by the fat body before pupation. These storage proteins play an important role in insect metamorphosis and egg development. Some of these storage proteins are responsive to pathogen infection and can even suppress pathogen multiplication. However, the mechanisms of the physiological, biochemical and immune-responsive functions of storage proteins remain unclear. In this study, the expression patterns of Bombyx mori storage protein 1 (BmSP1) during the larval stage were analysed. Then, BmSP1 protein fused with enhanced green fluorescent protein (EGFP) was successfully expressed in a B. mori baculovirus vector expression system. Quantitative real-time PCR showed that the expression level of BmSP1 increased with the advance of instars and reached the highest level in the fifth instar, especially in the fat body. Recombinant BmSP1 expressed in silkworm larvae inhibited haemolymph melanization. Then, proteins that interact with BmSP1 were identified with EGFP used as an antigenic determinant by co-immunoprecipitation. A 30 kDa low molecular weight lipoprotein PBMHP-6 precursor (BmLP6) was shown to interact with BmSP1. Yeast two-hybrid experiments confirmed the interaction between BmSP1 and BmLP6. The results obtained in this study will be helpful for further study of the functions of BmSP1 and BmLP6 in the regulatory network of silkworm development and innate immunity.
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http://dx.doi.org/10.1111/imb.12610DOI Listing
February 2020

Silkworm storage protein Bm30K-19G1 has a certain antifungal effects on Beauveria bassiana.

J Invertebr Pathol 2019 05 27;163:34-42. Epub 2019 Feb 27.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212018, China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212018, China. Electronic address:

Storage proteins in the 30 K family are ubiquitous in the hemolymph of insects and play important roles in adult metamorphosis, development, egg formation, carrier transport and even host immunity. Some studies have shown that the 30 K proteins can inhibit apoptosis and have certain antifungal effects. The silkworm protein Bm30K-19G1 is a low molecular weight apolipoprotein that is abundant in hemolymph of fifth instar larvae. Our previous transcriptome sequencing, real-time PCR analysis and proteomic studies showed that the expression level of the 30 K protein gene was significantly up-regulated in the silkworm infected with Beauveria bassiana. In this study, the ORF sequence of Bm30K-19G1 was amplified by PCR. The sequence is 1311 bp in length and encodes a 436 amino acid peptide. Bm30K-19G1 was expressed in all tested tissues of fifth instar larvae, with highest expression in fat body and the lowest expression in the midgut. Bm30K-19G1 protein was successfully expressed in the prokaryotic expression system using pET-28a(+) as vector and E. coli Arctic Express (DE3) as the expression bacterium strain. The expressed recombinant Bm30K-19G1 protein has an inhibitory effect on the conidial germination and hyphal growth of B. bassiana. Bm30K-19G1 also inhibited the growth and reproduction of B. bassiana in vivo; the median lethal time of infected silkworms was postponed by 6.4 h and the time for death of all infected larvae was postponed by 10 h. The results indicated that the silkworm storage protein 30K-19G1 is an antifungal protein against B. bassiana and help to elucidate the molecular mechanism of silkworm resistance against B. bassiana.
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http://dx.doi.org/10.1016/j.jip.2019.02.008DOI Listing
May 2019

The effect of pre-hospital intubation on prognosis in infants, children and adolescents with severe traumatic brain injury: A protocol of systematic review and meta-analysis.

Medicine (Baltimore) 2019 Feb;98(8):e14690

Department of Neurology, The First Hospital of Lanzhou, Lanzhou, China.

Introduction: Traumatic brain injury is one of the leading causes of death and sources of heavy societal burden. Hypoxemia and hypercapnia are the 2 common complications of brain injury. Intubation seems to be an effective intervention for preventing the 2 complications in pre-hospital setting. But the results of the existing studies on the effect of pre-hospital intubation on prognosis of patients (aged less than 18) with severe traumatic brain injury are conflict. Thus, in this study, we aim to conduct a systematic review and meta-analysis to evaluate whether pre-hospital intubation is benefit for the prognosis in infants, children and adolescents with severe traumatic brain injury.

Methods: We will develop a systematic search strategy which includes MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WanFang Data and China National Knowledge Infrastructure. The WHO International Clinical Trials Registry Platform will be searched for the ongoing studies as well. The cohort studies which aim to evaluate the effect of pre-hospital intubation for infants, children and adolescents with severe traumatic brain injury will be selected. The Newcastle-Ottawa Scale will be used for assessing the risk of bias of the included studies.

Results: The results of this study will be presented in the full-text of the systematic review.

Conclusion: This is the first systematic review and meta-analysis about evaluation of the effect of pre-hospital intubation on prognosis in infants, children and adolescents with traumatic brain injury.

Prespero Registration Number: CRD42019121214.
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http://dx.doi.org/10.1097/MD.0000000000014690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408067PMC
February 2019

Xueshuantong for Injection Ameliorates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Diabetes.

Chin J Physiol 2018 Dec;61(6):349-359

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, People’s Republic of China.

Diabetic nephropathy (DN) is a major complication of diabetes and becomes the chief cause of end-stage renal disease. Our study was undertaken to investigate the ameliorative effect and underlying mechanism of Xueshuantong for Injection (XST) on DN in streptozotocin (STZ)-induced rats. Effect of XST treatment (XST, 50 mg/kg/day, i.p.) lasting 60 days after STZ-induced (60 mg/kg, i.p.) diabetes was investigated. Blood sugar levels and body weight were recorded every week of the experiment. At the 28th and 56th days after injection urine glucose and 24 h urine protein excretion were determined. Apoptosis related factors such as cleaved caspase-3, Bcl-2, Bax and inflammation related factors, including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-1β, inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) were detected by PCR or western blot. The expression levels of fibronectin, Collagen Ⅰ, α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA), TGF-β-Smad2/3 signaling pathway, and receptor for advanced glycation end products (RAGE) was investigated. Our results showed that XST treatment did not affect levels of body weight, blood glucose and urine glucose levels. Our analysis revealed that XST inhibited cell apoptosis and suppressed the properties of RAGE in the kidney. XST treatment could also significantly suppress the overexpression of pro-inflammatory mediators in kidney and prevent renal fibrosis by blocking the TGF-β/Smad2/3 signaling pathway. In conclusion, our findings suggested that XST could provide protection against DN through reduction of RAGE accumulation, decreasing inflammation, inhibition of renal fibrosis, and blocking the TGF-β/Smad2/3 signaling pathway.
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http://dx.doi.org/10.4077/CJP.2018.BAH637DOI Listing
December 2018

Engineered RNase P Ribozymes Effectively Inhibit the Infection of Murine Cytomegalovirus in Animals.

Theranostics 2018 9;8(20):5634-5644. Epub 2018 Nov 9.

Department of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, China.

Gene-targeting ribozymes represent promising nucleic acid-based gene interference agents for therapeutic application. We previously used an selection procedure to engineer novel RNase P-based ribozyme variants with enhanced targeting activity. However, it has not been reported whether these ribozyme variants also exhibit improved activity in blocking gene expression in animals. In this report, R388-AS, a new engineered ribozyme variant, was designed to target the mRNA of assemblin (AS) of murine cytomegalovirus (MCMV), which is essential for viral progeny production. Variant R338-AS cleaved AS mRNA sequence at least 200 times more efficiently than ribozyme M1-AS, which originated from the wild type RNase P catalytic RNA sequence. In cultured MCMV-infected cells, R338-AS exhibited better antiviral activity than M1-AS and decreased viral AS expression by 98-99% and virus production by 15,000 fold. In MCMV-infected mice, R388-AS was more active in inhibiting AS expression, blocking viral replication, and improving animal survival than M1-AS. Our results provide the first direct evidence that novel engineered RNase P ribozyme variants with more active catalytic activity are also more effective in inhibiting viral gene expression in animals. Moreover, our studies imply the potential of engineering novel RNase P ribozyme variants with unique mutations to improve ribozyme activity for therapeutic application.
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http://dx.doi.org/10.7150/thno.27776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276291PMC
September 2019

Different Erythrocyte MicroRNA Profiles in Low- and High-Altitude Individuals.

Front Physiol 2018 14;9:1099. Epub 2018 Aug 14.

Department of Blood Transfusion, Chinese PLA General Hospital, Beijing, China.

The number of red blood cells (RBCs) increases significantly in response to high-altitude hypoxic environments, and the RBC microRNA (miRNA) expression pattern is similar to that in whole blood. Studies have shown that miRNA in plasma can act as a circulating hypoxia-associated marker, but the effect of a high-altitude hypoxic environment on RBC-derived miRNAs has not yet been reported. Blood samples were collected from 20 Han Chinese individuals residing at 500 m (Sichuan Han), 10 migrant Han Chinese citizens residing at 3,658 m (Tibet Han) and 12 native Tibetans, and RBC indices measurements and miRNA sequencing analyses were performed for the three sample groups. The levels of some markedly altered miRNAs at high altitude were subsequently measured from 5 randomly selected samples of each group by real-time PCR. Bioinformatic analyses was performed to determine the potential target genes of selected hypoxia-associated miRNAs. Marked changes of several RBC indices were observed among the Tibet Han population, the Tibetan population and the Sichuan Han population. A total of 516 miRNAs derived from RBCs were initially identified by miRNA sequencing in the three sample groups. Compared with the Sichuan Han population, 49 miRNAs were differentially expressed in the Tibet Han population (17 upregulated and 32 downregulated). 12 upregulated and 21 downregulated miRNAs were observed in the Tibetan population compared with the Sichuan Han population. A total of 40 RBC miRNAs were differentially expressed in the Tibetan population (15 upregulated and 25 downregulated) compared with the Tibet Han population. Two significantly altered miRNAs with the highest expression levels (miRNA-144-5p and miR-30b-5p) were selected for real-time PCR analysis, and the results were consistent with those of miRNA sequencing. Furthermore, bioinformatic analyses showed that some potential target genes of miR-144-5p and miR-30b-5p are involved in the erythroid- hypoxia-, and nitric oxide (NO)-related signaling pathways in response to hypoxia. Our findings provide clear evidence, for the first time, that a high-altitude hypoxic environment significantly affects human RBC miRNA profiles.
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http://dx.doi.org/10.3389/fphys.2018.01099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102482PMC
August 2018

RAGE antagonism by FPS‑ZM1 attenuates postoperative cognitive dysfunction through inhibition of neuroinflammation in mice.

Mol Med Rep 2017 Oct 21;16(4):4187-4194. Epub 2017 Jul 21.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China.

Neuroinflammation triggered by surgical trauma contributes to postoperative cognitive dysfunction (POCD). The receptor for advanced glycation end‑products (RAGE), a multiligand inflammatory receptor, is involved in the damaging effects of various cellular processes, contributing to neuroinflammation and neurodegeneration. However, the potential role of RAGE in the acute period of POCD has not been fully investigated. C57BL/6 male mice undergoing surgery of the tibia under isoflurane anesthesia were treated with the RAGE antagonist FPS‑ZM1 or vehicle control intraperitoneally for a period of 7 days. The cognitive function of the animals was tested using trace fear conditioning on the third postoperative day. To determine astrocytic activation, microgliosis, p65 expression, inflammatory factor levels and postsynaptic density protein‑95 (PSD‑95) expression in the hippocampus, the animals were euthanized on either the first, third or seventh postoperative day. Compared with the control group, the cognitive function of the surgical animals was impaired on the third postoperative day. Astrocytic activation, microgliosis and the expression levels of p65, interleukin (IL)‑1β, IL‑6, and PSD‑95 were significantly increased on the first, and third postoperative days. However, tumor necrosis factor‑α expression was significantly increased only on postoperative day 1. All of the surgical effects observed were partially inhibited by treatment with FPS‑ZM1. In summary, the results of the present study suggest that RAGE serves an important role in the acute inflammatory process of POCD, and blocking RAGE can inhibit neuroinflammation and attenuate POCD. Thus, the RAGE signaling pathway may be a novel target in the prevention, and treatment of POCD.
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http://dx.doi.org/10.3892/mmr.2017.7074DOI Listing
October 2017

Diosgenin glucoside provides neuroprotection by regulating microglial M1 polarization.

Int Immunopharmacol 2017 Sep 14;50:22-29. Epub 2017 Jun 14.

Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin 300193, China. Electronic address:

The selective suppression of inflammatory factors in activated microglia, rather than totally inhibiting their activation, might be an effective means of slowing the progression of certain neurodegenerative diseases. Diosgenin glucoside (Dios) is a saponin compound extracted from Tritulus terrestris L. We found that Dios suppressed the synthesis of molecules that promote inflammation (M1 markers, such as NO, IL-6, and TNF-α) in rat microglia and BV-2 cells induced with lipopolysaccharides (LPS). In contrast, Dios had no effects on the cellular production of anti-inflammatory factors (M2 markers, such as IL-10, IL-1Rα and CD206) in LPS and IL-4 treated microglia. Dios repressed IκB-α, ERK MAPK and p38 MAPK phosphorylation, but did not affect JNK in LPS-activated microglia. We also found that conditioned medium obtained from cultures of BV-2 cells incubated with Dios plus LPS was markedly less neurotoxic than conditioned medium obtained from cultures of BV-2 cells incubated with LPS alone. In conclusion, this study demonstrated that Dios can selectively suppress the production/expression of pro-inflammatory M1 markers by activated microglia, without affecting M2 markers, and might provide neuroprotection by regulating microglial M1 polarization. Our results suggest that Dios can be used in treatment of various neuroinflammatory diseases mediated by microglia.
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http://dx.doi.org/10.1016/j.intimp.2017.06.008DOI Listing
September 2017

Efficient Fetal-Maternal ECG Signal Separation from Two Channel Maternal Abdominal ECG via Diffusion-Based Channel Selection.

Front Physiol 2017 16;8:277. Epub 2017 May 16.

Department of Mathematics, University of TorontoToronto, ON, Canada.

There is a need for affordable, widely deployable maternal-fetal ECG monitors to improve maternal and fetal health during pregnancy and delivery. Based on the diffusion-based channel selection, here we present the mathematical formalism and clinical validation of an algorithm capable of accurate separation of maternal and fetal ECG from a two channel signal acquired over maternal abdomen. The proposed algorithm is the first algorithm, to the best of the authors' knowledge, focusing on the fetal ECG analysis based on two channel maternal abdominal ECG signal, and we apply it to two publicly available databases, the PhysioNet non-invasive fECG database (adfecgdb) and the 2013 PhysioNet/Computing in Cardiology Challenge (CinC2013), to validate the algorithm. The state-of-the-art results are achieved when compared with other available algorithms. Particularly, the score for the R peak detection achieves 99.3% for the adfecgdb and 87.93% for the CinC2013, and the mean absolute error for the estimated R peak locations is 4.53 ms for the adfecgdb and 6.21 ms for the CinC2013. The method has the potential to be applied to other fetal cardiogenic signals, including cardiac doppler signals.
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http://dx.doi.org/10.3389/fphys.2017.00277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432652PMC
May 2017

MetaSpark: a spark-based distributed processing tool to recruit metagenomic reads to reference genomes.

Bioinformatics 2017 04;33(7):1090-1092

Computer Network Information Center of Chinese Academy of Sciences, Beijing, China.

Summary: With the advent of next-generation sequencing, traditional bioinformatics tools are challenged by massive raw metagenomic datasets. One of the bottlenecks of metagenomic studies is lack of large-scale and cloud computing suitable data analysis tools. In this paper, we proposed a Spark based tool, called MetaSpark, to recruit metagenomic reads to reference genomes. MetaSpark benefits from the distributed data set (RDD) of Spark, which makes it able to cache data set in memory across cluster nodes and scale well with the datasets. Compared with previous metagenomics recruitment tools, MetaSpark recruited significantly more reads than many programs such as SOAP2, BWA and LAST and increased recruited reads by ∼4% compared with FR-HIT when there were 1 million reads and 0.75 GB references. Different test cases demonstrate MetaSpark's scalability and overall high performance.

Availability: https://github.com/zhouweiyg/metaspark.

Contact: bniu@sccas.cn , jingluo@ynu.edu.cn.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btw750DOI Listing
April 2017

Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells.

Int J Mol Sci 2016 Apr 15;17(4):563. Epub 2016 Apr 15.

Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China.

Human epidermal growth factor receptor 2 (HER2) is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21) is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21) that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra), markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.
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http://dx.doi.org/10.3390/ijms17040563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849019PMC
April 2016

Sirtuin 6 is essential for sodium sulfide-mediated cytoprotective effect in ischemia/reperfusion-stimulated brain endothelial cells.

J Stroke Cerebrovasc Dis 2015 Mar 24;24(3):601-9. Epub 2014 Dec 24.

Department of Pharmacology, Anhui Medical University, Hefei, China.

Background: Our recent data demonstrated that hydrogen sulfide (H2S), the third gaseous transmitter, had a protective effect on stroke. The purpose of this study was to investigate the protective effect of H2S in oxygen glucose deprivation and reperfusion (OGD/R)-stimulated brain endothelial cells and its association with sirtuin 6 (SIRT6).

Methods: Cultured bEnd.3 brain endothelial cells were exposed to OGD/R. The effects of sodium sulfide (Na2S, an exogenous H2S donor) on cell death, lactate dehydrogenase release, intracellular reactive oxygen species (ROS) production, superoxide dismutase (SOD) and catalase (CAT) activities, H2S level, cystathionine γ-lyase (CSE) expression, and sirtuin 6 (SIRT6) expression/activity were tested to elucidate the protective mechanisms of H2S.

Results: Application of Na2S concentration dependently reduced OGD/R-induced cell death, accompanying with decreasing intracellular ROS production and increasing activities of SOD and CAT. In addition, Na2S also enhanced H2S level and CSE expression associated with upregulation of SIRT6 expression and activity in OGD/R-stimulated brain endothelial cells, whereas CSE inhibitor DL-propargylglycine further deteriorated the decrease of SIRT6 expression and activity as well as the reduction of H2S level and CSE expression caused by OGD/R. Furthermore, SIRT6 knockdown abolished Na2S-mediated CSE expression and cytoprotection action in OGD/R-stimulated cells.

Conclusions: Na2S protected brain endothelial cells against simulated ischemic injury through SIRT6-dependent mechanisms.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.10.006DOI Listing
March 2015

[Establishment of animal model of a human lung adenocarcinoma drug-resistant
cell line Anip973/NVB and investigation on mechanism of drug resistance].

Zhongguo Fei Ai Za Zhi 2012 Mar;15(3):146-51

Department of Medical Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150081, China.

Background And Objective: Multidrug resistance (MDR) is the main cause of chemotherapeutic failure in lung cancer, and vinorelbine (NVB) is one of the most efficient drugs that threaten non-small cell lung cancer (NSCLC). The current study aims to establish tumor xenografts and investigate the molecular mechanisms involved in the resistance of NVB in lung adenocarcinoma.

Methods: Nude mice were implanted with Anip973 and Anip973/NVB, and tumor-bearing mice were divided into the Anip973 treatment, Anip973 control, Anip973/NVB treatment, and Anip973/NVB control groups, respectively. The current study observes tumor growth, draws growth curves, and calculates inhibitory rates. The morphological changes in cell tumor were observed through the immunohistochemical method using an electron microscope to detect the expressions of MRP3 and Bcl-2 and to investigate the molecular mechanisms of Anip973/NVB cells.

Results: The tumor inhibitory rates of the Anip973 and Anip973/NVB cells treated with NVB were 60.00% and 4.65%, respectively, compared with the control group. The growth inhibition in the Anip973/NVB cell transplantation tumor had no significant difference. Apoptosis was observed using TEM when the Anip973 transplantation tumor was treated with NVB. On the other hand, no apoptosis was found in the Anip973/NVB transplantation tumor using TEM. Immunohistochemical staining (SP) shows the positive expressions of Bcl-2 and MRP3 proteins in Anip973/NVB transplantation tumor, which were observed to be higher than those in the Anip973 transplantation tumor.

Conclusions: The overexpression of Bcl-2 and MRP3 might be one of the major mechanisms of the MDR of Anip973/NVB.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2012.03.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999873PMC
March 2012

Angelica injection promotes peripheral nerve structure and function recovery with increased expressions of nerve growth factor and brain derived neurotrophic factor in diabetic rats.

Curr Neurovasc Res 2010 Aug;7(3):213-22

Department of Neurology, Zhongnan Hospital, Wuhan University, No 169 Donghu Road, Wuchang District, Wuhan, China.

Several nervous system injury models, such as sciatic crush and chronic cerebral hypoperfusion have been well studied in terms of neuroprotective effect of angelica injection. However, definitive experimental studies are lacking on diabetic peripheral neuropathy (DPN). This study sought to investigate the effects of angelica injection on DPN in type 1 diabetic rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). To examine whether DPN model succeeded, tail-flick latency (TFL) and motor nerve conduction velocity (MNCV) were measured at 6 weeks after diabetes induction. Then, diabetic rats were treated with high- and low-dose angelica injection for 4 weeks. TFL, MNCV, morphology of sciatic nerve, myelinated nerve fiber density and the expressions of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in soleus and sciatic nerve were measured at 10 weeks after diabetes induction. The results showed the TFL was significantly shortened (p<0.001) and the MNCV was reduced (p<0.01) in diabetic rats compared with normal control rats at 6 weeks after diabetes induction. The TFL was obviously prolonged and the MNCV was further reduced in diabetic control group at 10 weeks after diabetes induction. TFL, MNCV and morphology of sciatic nerve were remarkably ameliorated and myelinated nerve fiber density and the expressions of NGF and BDNF in soleus and sciatic nerve were increased in the angelica treatment groups. This study suggests angelica injection has potential therapeutic effects on DPN, and the mechanism might be related to direct increase in NGF expression and direct or indirect increase in BDNF expression.
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http://dx.doi.org/10.2174/156720210792231796DOI Listing
August 2010

Mental retardation and Xq12-Xq23: candidate loci for nonspecific mental retardation in the male population of the QinBa region.

Psychiatr Genet 2009 Feb;19(1):27-31

College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Objectives: The higher prevalence of nonspecific mental retardation (NSMR) presents an important socioeconomic and medical issue for families and the whole QinBa region in China. The obvious family aggregation and high heritability indicated that genetic causes play a role in the NSMR population in QinBa. This study discusses the relationship between Xq12-Xq23 region and NSMR in the QinBa area.

Method: We chose six short tandem repeats--DXS7132, DXS6979, DXS1191, DXS1230, DXS1072, and DXS6804, located in Xq12-Xq23--and analyzed the distribution difference of their alleles between the NSMR and control boys.

Results: A significant allele distribution difference was found between NSMR and control boys (all P<0.05) for DXS7132, DXS1191, DXS1230, DXS1072, and DXS6804 but not for DXS6979.

Conclusion: Our results suggest that Xq12-Xq23 may be the candidate region where there are one or more loci, linked to NSMR in the QinBa region. Further study needs to be carried out for locating the gene responsible for NSMR in this region and a larger sample size and more genetic markers are needed.
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http://dx.doi.org/10.1097/YPG.0b013e3283121d05DOI Listing
February 2009