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| 1 | Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma显示文摘Glioblastoma(GBM)is an incurable and highly heterogeneous brain tumor,originating from human neural stem/progenitor cells(hNSCs/hNPCs)years ahead of diagnosis.Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels,the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling.Here,we established two highly penetrant hNSC-derived malignant glioma models,which resemble the histopathology and transcriptional heterogeneity of human GBM.Integrating time-series analyses of whole-exome sequencing,bulk and single-cell RNA-seq,we reconstructed gliomagenic trajectories,and identified a persistent NSC-like population at all stages of tumorigenesis.Through trajectory analyses and lineage tracing,we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells,which sequentially generate malignant heterogeneity and induce tumor phenotype transitions.We further uncovered stage-specific oncogenic cascades,and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor.Importantly,the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations,during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis.Together,our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs,and provide a blueprint for potential early-stage treatment/diagnosis for GBM. | Xiaofei Wang Ran Zhou Yanzhen Xiong Lingling Zhou Xiang Yan Manli Wang Fan Li Chuanxing Xie Yiming Zhang Zongyao Huang Chaoqiong Ding Kaidou Shi Weida Li Yu Liu Zhongwei Cao Zhen-Ning Zhang Shengtao Zhou Chong Chen Yan Zhang Lu Chen Yuan Wang | 2021 | Cell Research2021，31，6： | 8 |
| 2 | Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine显示文摘Realizing personalized medicine requires integrating diverse data types with bioinformatics.The most vital data are genomic information for individuals that are from advanced next-generation sequencing(NGS) technologies at present.The technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the data.The prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work alike.Bioinformatics is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized medicine.We review some key bioinformatics tasks,issues,and challenges in contexts of IT requirements,data quality,analysis tools and pipelines,and validation of biomarkers. | HONG HuiXiao ZHANG WenQian SHEN Jie SU ZhenQiang NING BaiTang HAN Tao PERKINS Roger SHI LeMing TONG WeiDa | 2013 | Science China(Life Sciences)2013，56，2： | 7 |
| 3 | Oral vaccination of mice against rodent malaria with recombinant Lactococcus lactis expressing MSP-1_(19)显示文摘瞄准:构造 recombinant Lactococcus 乳酸作为对疟疾的口头的交货种痘。方法:变形体 yoelii 265-BY 的 MSP1 (MSP-1 (19 )) 的 C 终端 19-ku 碎片在 L 被表示。乳酸是并且 recombinant L。乳酸是予 BALB/c 和 C57BL/6 老鼠口头上地被以。在在 4 wk 以内的七间隔种痘以后,老鼠与 P 被质问。红细胞舞台的 yoelii 265-BY 寄生虫。recombinant L 的保护的功效。乳酸被评估。结果:分别地,在为 BALB/c 和 C57BL/6 鼠标的实验组的一般水准的山峰 parasitemias 是 0.8+/-0.4% 和 20.8+/-26.5% ,他们的控制组的那些分别地是 12.0+/-0.8% 和 60.8+/-9.6% 。任何一个都没在实验期间死于在试验性的组和控制组的 BALB/c 老鼠。然而,在控制组的所有 C57BL/6 鼠标在 23 d 和熬过很好的所有种牛痘的鼠标以内死了。结论:结果暗示 recombinant L 的潜力。乳酸作为对疟疾的口头的交货种痘。 | Zhi-Hong Zhang Pei-Hong Jiang Ning-Jun Li Mi Shi Weida Huang | 2005 | World Journal of Gastroenterology2005，11，44： | 4 |
| 4 | [Corrigendum] Cidan inhibits liver cancer cell growth by reducing COX-2and VEGF expression and cell cycle arrest显示文摘 | Nan Li Donghai Zheng Jie Xue Weixing Guo Jie Shi Juxian Sun Chongde Lu Weida Zheng Mengchao Wu Shuqun Cheng | 2015 | Experimental and Therapeutic Medicine2015，，4： | 1 |
| 5 | Review: bio-based films from zein, keratin, pea, and rapeseed protein feedstocks显示文摘 | Weida Shi Marie-Josée Dumont | 2014 | Journal of Materials Science2014，，5： | 1 |
| 6 | Significant variations in alternative splicing patterns and expression profiles between human-mouse orthologs in early embryos显示文摘Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development. | Geng Chen Jiwei Chen Jianmin Yang Long Chen Xiongfei Qu Caiping Shi Baitang Ning Leming Shi Weida Tong Yongxiang Zhao Meixia Zhang Tieliu Shi | 2017 | Science China(Life Sciences)2017，60，2： | 1 |
| 7 | Sequencing XMET genes to promote genotype-guided risk assessment and precision medicine显示文摘High-throughput next generation sequencing (NGS) is a shotgun approach applied in a parallel fashion by which the genome is fragmented and sequenced through small pieces and then analyzed either by aligning to a known reference genome or by de novo assembly without reference genome.This technology has led researchers to conduct an explosion of sequencing related projects in multidisciplinary fields of science.However,due to the limitations of sequencing-based chemistry,length of sequencing reads and the complexity of genes,it is difficult to determine the sequences of some portions of the human genome,leaving gaps in genomic data that frustrate further analysis.Particularly,some complex genes are difficult to be accurately sequenced or mapped because they contain high GC-content and/or low complexity regions,and complicated pseudogenes,such as the genes encoding xenobiotic metabolizing enzymes and transporters (XMETs).The genetic variants in XMET genes are critical to predicate interindividual variability in drug efficacy,drug safety and susceptibility to environmental toxicity.We summarized and discussed challenges,wet-lab methods,and bioinformatics algorithms in sequencing 'complex' XMET genes,which may provide insightful information in the application of NGS technology for implementation in toxicogenomics and pharmacogenomics. | Yaqiong Jin Geng Chen Wenming Xiao Huixiao Hong Joshua Xu Yongli Guo Wenzhong Xiao Tieliu Shi Leming Shi Weida Tong Baitang Ning | 2019 | Science China(Life Sciences)2019，62，7： | 1 |
| 8 | QuaPra: Efficient transcript assembly and quantification using quadratic programming with Apriori algorithm显示文摘RNA sequencing(RNA-seq) has greatly facilitated the exploring of transcriptome landscape for diverse organisms.However,transcriptome reconstruction is still challenging due to various limitations of current tools and sequencing technologies.Here,we introduce an efficient tool,QuaPra(Quadratic Programming combined with Apriori),for accurate transcriptome assembly and quantification.QuaPra could detect at least 26.5% more low abundance(0.1–1 FPKM) transcripts with over 2.7% increase of sensitivity and precision on simulated data compared to other currently popular tools.Moreover,around one-quarter more known transcripts were correctly assembled by QuaPra than other assemblers on real sequencing data.QuaPra is freely available at http://gffzz964817d90372402ahvokwc9xw99kf665q.ffgz.tsg.suse.edu.cn/QuaPra/. | Xiangjun Ji Weida Tong Baitang Ning Christopher E. Mason David P. Kreil Pawel P. Labaj Geng Chen Tieliu Shi | 2019 | Science China(Life Sciences)2019，62，7： | 1 |
| 9 | Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells显示文摘Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D. | Gang Liu Yana Li Tengjiao Zhang Mushan Li Sheng Li Qing He Shuxin Liu Minglu Xu Tinghui Xiao Zhen Shao Weiyang Shi Weida Li | 2021 | Genomics, Proteomics & Bioinformatics2021，19，3： | 1 |
| 10 | Identification and Biological Characteristics of Edwardsiella tarda Isolated from Pelteobagrus fulvidraco显示文摘Over the past five years,an epidemic disease broke out in Pelteobagrus fulvidraco ponds of Zhejiang Province. The diseased fish mainly exhibits head splitting and surface bleeding; dissection results reveal hepatonephromegaly and abdominal bleeding. A bacterial strain HSY201301 was isolated from the liver tissue of P. fulvidraco with typical symptoms. Artificial infection experiment confirmed that the isolated strain had a strong virulence to healthy P. fulvidraco,leading to similar symptoms to naturally infected P. fulvidraco. The isolated strain was identified as an Edwardsiella tarda strain according to conventional morphological,physiological,biochemical characteristics and 16 S rRNA gene sequence. Results of drug susceptibility test indicated that the isolated strain was sensitive to ciprofloxacin,doxitard,penicillin,doxycycline,and rocephin. This study laid solid foundation for effective prevention and control of E. tarda. | Dongren ZHOU Xueping YE Yizhi LUO Weida SHI Xiaoying HANG | 2014 | Agricultural Biotechnology2014，3，5： | 1 |
| 11 | Hsa_circ_0002137 stabled by LIN28B promotes osteosarcoma cell growth through the hsa-miR-1246/BCL2 axis显示文摘Circular RNAs(circRNAs)are a novel class of non-coding RNA that have recently shown to have huge capabilities in the regulation of gene expression at the posttranscriptional level.Growing evidence has indicated that circRNAs could serve as competing endogenous RNAs(ceRNAs)to sponge microRNAs(miRNAs)and suppress functions of targeted miRNAs.Osteosarcoma(OS)is the most common malignant primary bone cancer.Hsa_circ_0002137 is upregulated in OS.However,the role of hsa_circ_0002137 in OS remains unclear.Using miRNA pull-down assay,we showed that cir_0002137 sponged hsa-miR-1246,and BCL2 apoptosis regulator(BCL2)mRNA was a potential target of hsa-miR-1246 in human osteosarcoma(HOS)cells.Further,we found that hsa_cir_0002137 could enhance the expression of BCL2 hsa-miR-1246 and promote HOS cell growth through sponging hsa-miR-1246.Moreover,RNA binding protein immunoprecip itation(RIP)assay revealed that lin-28 homolog B(LIN28B)protein associated with hsa_circ_0002137,and LIN28B could increase hsa_circ_0002137 stability and thus accelerate OS cell growth.Our work was the first to study the functions of hsa_circ_0002137,has-miR-1246 and LIN28B in OS,and these results may provide novel therapeutic targets for OS treatment. | FEI ZHANG JIANZHONG LAI RONGHAN HE YI SHI KUN XU SHIHAI JIANG TANGZHAO LIANG WANYU ZHAO WEIDA REN LEI ZHU SONG JIN KUN WANG | 2022 | BIOCELL2022，46，3： | 0 |
| 12 | Single-cell RNA-sequencing and subcellular spatial transcriptomics facilitate the translation of liver microphysiological systems for regulatory application显示文摘Reducing the use of animal models in drug development and safety assessment has long been supported by the U.S.Food and Drug Administration(FDA).The report by Royal Society for the Prevention of Cruelty to Animals indicates that in 2020,experiments involved the use of over 100 million animals,with the United States leading the list by utilizing 20 million animals.Beyond ethical considerations associated with animal testing and the costs in terms of time and money,animal models are not always effective in predicting human reactions to drug exposure.While animal testing has been the traditional method for assessing the safety and efficacy of drugs. | Dan Li Zhou Fang Qiang Shi Nicholas Zhang Binsheng Gong Weida Tong Ahmet F.Coskun Joshua Xu | 2023 | Journal of Pharmaceutical Analysis2023，13，7： | 0 |
| 13 | Application of a recombinant replicase to localize the Trionyx sinensis hemorrhagic syndrome virus and evaluate its effects on antiviral genes of T.sinensis显示文摘Trionyx sinensis Hemorrhagic Syndrome Virus(TSHSV)is an arterivirus newly discovered in Chinese softshell turtles.Little is known about the effect of antibodies against the virus or the distribution of the virus in different organs of infected turtles.In this study,a partial protein of TSHSV-HP4 was produced using a prokaryotic expression system,and its polyclonal antibody was generated.The polyclonal antibody was confirmed by western blot and dot enzyme-linked immunosorbent assay(dot-ELISA).The distribution of TSHSV in different organs of T.sinensis was examined by immunohistochemistry(IHC)and the expression of immune-related genes was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).The results indicated that the recombinant TSHSV-HP4 protein was successfully expressed,and the generated polyclonal antibody showed specific binding to viral particles in the lung tissues of infected turtles.The IHC assay indicated that the virus was highly localized in various cells,including intestinal lymphocytes,enterocytes,kidney epithelial cells,spleen cells,lung macrophages,and cardiomyocytes.The qRT-PCR analysis revealed that TSHSV was detected in all organs tested,including the lungs,liver,kidneys,spleen,and heart.The numbers of viral mRNA copies in lung and heart tissues were significantly higher in the virus-antibody group than in the virus group.The interferonstimulated genes(ISGs),myxovirus resistance protein 2(MX2)and radical S-adenosyl methionine domain containing 2(RSAD2)were highly upregulated in all groups of infected turtles.Antibody-dependent enhancement(ADE)seemed to occur after stimulation by the polyclonal antibody,because significantly greater expression of the two genes was detected in the virus-antibody group than in the virus group.Overall,these results are important in understanding the cell localization of TSHSV and the immune response of infected turtles. | Sunjian LYU Xuemei YUAN Li LIU Haiqi ZHANG Zhe YU Xiaoying HANG Weida SHI Yinglei WU | 2021 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2021，22，4： | 0 |
| 14 | Erratum to:Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine显示文摘 | HONG HuiXiao ZHANG WenQian SHEN Jie SU ZhenQiang NING BaiTang HAN Tao PERKINS Roger SHI LeMing TONG WeiDa | 2013 | Science China(Life Sciences)2013，56，3： | 0 |
| 15 | Isolation and Identification of the Pathogens of Bullfrog Streptoccus Disease显示文摘The tested strain from typical clinical cases,and the physio-chemical characteristics,16 S rRNA gene sequence and drug sensitivity challenge property were analyzed.This isolate was determined as Streptococcus agalactiae,16 S rRNA gene fragment of 1 280 bp in length.Blast analysis showed that this fragment shared a 100% homology with the conservative region of Streptococcus agalactiae isolate(AB023574),Streptococcus dysqalactiae isolate(HM146084.1,AB537922,EU075033),Streptococcus difficilis isolate(AB112407) accessed in Genbank.The isolate was sensitive to ciprofloxacin,neomycin,spectinomycin,furadantin and enoxacin.The results lay foundation for the effective control,rational medication and vaccine preparation for Streptococcus disease on bullfrogs. | Hang Xiaoying Zhou Dongren Luo Yizhi Shi Weida Ye Xueping | 2015 | Animal Husbandry and Feed Science2015，7，1： | 0 |
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