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| 1 | A GATA-type transcription factor AcAREB for nitrogen metabolism is involved in regulation of cephalosporin biosynthesis in Acremonium chrysogenum显示文摘In filamentous fungi,nitrogen metabolism is repressed by GATA-type zinc finger transcription factors.Nitrogen metabolite repression has been found to affect antibiotic production,but the mechanism is still poorly understood.AcareB,encoding a homologue of fungal GATA-type regulatory protein,was cloned from Acremonium chrysogenum.Gene disruption and genetic complementation demonstrated that AcareB plays a key role in utilization of ammonium,glutamine and urea.In addition,significant reduction of cephalosporin production in the AcareB disruption mutant indicated that AcareB is important for cephalosporin production.In consistence with it,the transcriptional level of cephalosporin biosynthetic genes was significantly decreased in the AcareB disruption mutant.Electrophoretic mobility shift assay showed that AcAREB directly bound to the intergenic regions of pcbAB-pcbC,cefD1-cefD2 and cefEF-cefG.Sequence analysis showed that all the AcAREB binding sites contained the consensus GATA elements.AcareB is negatively autoregulated during cephalosporin production.Moreover,another GATA zinc-finger protein encoded by AcareA positively regulates the transcription of AcareB.However,AcareB does not regulate the transcription of AcareA.These results indicated that AcAREB plays an important role in both regulation of nitrogen metabolism and cephalosporin production in A.chrysogenum. | Feifei Guan Yuanyuan Pan Jinyang Li Gang Liu | 2017 | Science China(Life Sciences)2017，60，9： | 8 |
| 2 | Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance显示文摘Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);however,after 10-12 months,secondary mutations arise that confer resistance.We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK-and EGFR-targeted TKIs crizotinib and osimertinib,respectively.Methods:Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing(WES),and patients and xenograft-bearing mice received targeted treatment(crizotinib or osimertinib)accordingly.Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size.Finally,the pathology of patients biopsies and xenograft tumors were compared histologically.Results:The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients.WES showed that the genotypes of the xenograft and patient tumors were similar(an echinoderm microtu-bule-associated protein-like 4-ALK(EML4-ALK)gene fusion(patient/xenograft:CTC15035EML4-ALK)and EGFR L858R and T790M mutations(patient/xenograft:CTC15063EGFR L858R,T790M)).After continuous crizotinib or osimertinib treatment,WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft,while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B(BRAF)G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha(PIK3C2A)A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R,T790M xenografts.Conclusions:We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology,which might be a useful tool to investigate the mechanisms of drug resist-ance in NSCLC. | Yunhua Xu Feifei Zhang Xiaoqing Pan Guan Wang Lei Zhu Jie Zhang Danyi Wen Shun Lu | 2018 | Cancer Communications2018，38，1： | 7 |
| 3 | Knock in of a hexanucleotide repeat expansion in the C9orf72 gene induces ALS in rats显示文摘Background:The GGGGCC(G4C2)repeat expansion in the human open reading frame 72 on chromosome 9,C9orf72,is the most common cause of amyotrophic lateral sclerosis(ALS).Studies in transgenic mouse models have linked the pathogenic mechanism of G4C2 repeat expansion to RNA foci or the accumulation of unnatural dipeptide repeats in neurons.However,only one of the existing transgenic mouse lines developed typical ALS.Methods:C9orf72 knockin rats were generated by knockin of 80 G4C2 repeats with human flanking fragments within exon1a and exon1b at the rat C9orf72 locus.Protein expression was detected by western blot.Motor coordination and grip force were measured using a Rotarod test and a grip strength test.Neurodegeneration was assessed by Nissl staining with cresyl violet.Results:C9orf72 haploinsufficiency reduced C9orf72 protein expression 40%in the cerebrum,cerebellum and spinal cords from knockin rats(P<.05).The knockin(KI)rats developed motor deficits from 4 months of age.Their falling latencies and grip force were decreased by 67%(P<.01)and 44%(P<.01),respectively,at 12 months of age compared to wild-type(WT)mice.The knockin of the hexanucleotide repeat expansion(HRE)caused a 47%loss of motor neurons in the spinal cord(P<.001)and 25%(5/20)of female KI rats developed hind limb paralysis at 13 to 24 months.Conclusion:Motor defects in KI rats may result from neurotoxicity caused by HRE and the resulting reduction in C9orf72 protein due to haploinsufficiency.These KI rats could be a useful model for investigating the contributions of loss-of-function to neurotoxicity in C9orf72-related ALS. | Wei Dong Li Zhang Caixian Sun Xiang Gao Feifei Guan Jing Li Wei Chen Yuanwu Ma Lianfeng Zhang | 2020 | Animal Models and Experimental Medicine2020，3，3： | 2 |
| 4 | Securities regulation and implicit penalties显示文摘The extant literature offers extensive support for the significant role played by institutions in financial markets,but implicit regulation and monitoring have yet to be examined.This study fills this void in the literature by employing unique Chinese datasets to explore the implicit regulation and penalties imposed by the Chinese government in regulating the initial public offering(IPO) market.Of particular interest are the economic consequences of underwriting IPO deals for client firms that violate regulatory rules in China's capital market.We provide evidence to show that the associated underwriters' reputations are impaired and their market share declines.We further explore whether such negative consequences result from a market disciplinary mechanism or a penalty imposed by the government.To analyze the possibility of a market disciplinary mechanism at work,we investigate(1) the market reaction to other client firms whose IPO deals were underwritten by underwriters associated with a violation at the time the violation was publicly disclosed and(2) the under-pricing of IPO deals undertaken by these underwriters after such disclosure.To analyze whether the government imposes an implicit penalty,we examine the application processing time for future IPO deals underwritten by the associated underwriters and find it to be significantly longer than for IPO deals underwritten by other underwriters.Overall,there is little evidence to suggest that the market penalizes underwriters for the rule-violating behavior of their client firms in China.Instead,the Chinese government implicitly penalizes them by imposing more stringent criteria on and lengthening the processing time of the IPO deals they subsequently underwrite. | Donghua Chen Yuyan Guan Gang Zhao Feifei Wu | 2011 | China Journal of Accounting Research2011，，Z1： | 2 |
| 5 | Novel rat model of multiple mitochondrial dysfunction syndromes(MMDS)complicated with cardiomyopathy显示文摘Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs. | Yahao Ling Jiaxin Ma Xiaolong Qi Xu Zhang Qi Kong Feifei Guan Wei Dong Wei Chen Shan Gao Xiang Gao Shuo Pan Yuanwu Ma Dan Lu Lianfeng Zhang | 2021 | Animal Models and Experimental Medicine2021，4，4： | 2 |
| 6 | Combination of two lipases more efficiently catalyzes methanolysis of soy- bean oil for biodiesel production in aqueous medium 显示文摘 | GUAN Feifei PENG Pu WANG Guili | 2010 | Process Biochem2010，45，10： | 1 |
| 7 | Haspin氨基端非激酶域与Pds5B的结合在有丝分裂期保护着丝粒区姐妹染色体粘连显示文摘文章简介黏连蛋白复合体(cohesin)维持姐妹染色单体配对,并促进染色体与纺锤体的正确连接。在有丝分裂的初期,染色体臂上的cohesin在其调节亚基Wapl的作用下被大量地去除,而着丝粒区的cohesin必须得以保留才能防止染色体的错误分离。 | Linli Zhou Cai Liang Qinfu Chen Zhenlei Zhang Bo Zhang Haiyan Yan Feifei Qi Miao Zhang Qi Yi Youchen Guan Xingfeng Xiang Xiaoqing Zhang Sheng Ye 汪方炜 | 2018 | 科学新闻2018，0，4： | 0 |
| 8 | Delta.AR:An augmented reality-based visualization platform for 3D genome显示文摘Many visualization tools have been developed for 3D genome data integration using two-dimensional(2D)devices such as PC monitors or smartphones.However,the 2D surface is only suitable for displaying linear data,and it has done little to inform our understanding of the complex interconnections between 3D genome architecture and its various associated-omics data.The breakthrough in immersive display technologies,e.g.,virtual reality(VR)and augmented reality(AR),has opened a completely new model for data visualization.Immersive visualization has proved a powerful way to enhance 3D structure-related research,e.g.,protein structure and drug design.However,visualization in immersive mode,coupled with the integration of 3D genome and its associated-omics data,is challenging.Only a few attempts have been made for single features,e.g.,Juicebox VR,which projects a Hi-C contact matrix into a virtual mountain field,and the WashU Epigenome Browser,which provides a 3D scene for epigenome tracks.A visualization tool for immersive integration of 3D genome architecture with high-dimensional-omics data has not yet been published. | Bixia Tang Xiaoxing Li Guan Li Dong Tian Feifei Li Zhihua Zhang | 2021 | The Innovation2021，2，3： | 0 |
| 9 | Cultivating global health professionals: evaluation of a training course to develop international consulting service competence in China显示文摘Background:China’s accelerating development and increasingly important role in global health engagement create a great demand for global health professionals including international consulting experts.This study reported the detailed development and evaluation of an international consulting training for global health workforce.Methods:Based on Kirkpatrick’s model,a mixed-methods approach was used to evaluate the effectiveness of the training.Quantitative and qualitative data on participants’reaction,learning,and application of the learned knowledge and skills were collected by a training evaluation survey at the ending of training and a follow-up interview in three months after the training.Results:Thirty-six participants attended the training and 34 of them completed quantitative investigation.The training satisfaction evaluations were positive,for which participants rated the training program highly and over 90%of them agreed with the usefulness of the training.About knowledge and skills change,participants showed improved consulting knowledge and skills from pre-to post-training(P<0.001).A total of 23 participants accepted follow-up interview,and most participants applied knowledge and skills learned from the training in their daily work or study.However,only 30.4%of participants applied their learning in the consulting program.The largest barrier of application was the lack of consulting opportunities.In addition,almost all the participants reported that they would be glad to attend more training courses in the future.Conclusion:The international consulting training program was well-received,and was feasible to improve the consulting service competence of global health professionals.According to participants’feedback,it is essential to develop and expand consulting training in the field of global health. | Pan Gao Li Guan Yisi Liu Feifei Liu Wenyuan Yu Xiangyu Li Suyang Liu Yuanan Lu Hao Li Hao Xiang | 2020 | Global Health Journal2020，4，2： | 0 |
| 10 | Analysis of Nitrogen Metabolism Related Enzymes and Related Physiological Indexes of Main Foxtail Millet Varieties Developed in North China显示文摘[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carried out on 20 main foxtail millet varieties promoted in North China developed from the 1980 s to 2000 s. The physiological and biochemical indexes of different foxtail millet varieties in four ages were compared, including chlorophyll content, soluble protein content, glutamine synthetase(GS) activity and glutamate synthase(GOGAT) activity, and the correlation between enzyme activity and yield was analyzed. [Results] The chlorophyll SPAD values of the flag leaf and functional leaves of foxtail millet varieties decreased with the filling process. The SPAD values of the flag leaf, top second leaf and top third leaf were higher in the varieties developed in the 1990 s and 2000 s than those in the 1980 s and 2010 s. The activity of glutamine synthetase(GS) and glutamate synthase(GOGAT) showed a single-peak curve in different foxtail millet varieties developed in the recent 30 years, and the peaks of the two were at 7 d and at 7 or 14 d, respectively. The activity of GS and GOGAT increased with the breeding age. In the period from 7 d after anthesis to the mature period, the decreases in the soluble protein content followed an order of 2010 s, 2000 s, 1990 s and 1980 s from small to large, indicating that the degradation rate of various enzyme sources and metabolic regulators in foxtail millet plants decreased during the improvement process. At 35 d after anthesis, the correlation coefficient between GS activity and yield was-0.247, that is, there was a negative correlation with yield. And there was a significant positive correlation between GOGAT activity and yield, and the correlation coefficient was as high as 0.455 at 7 d after anthesis. [Conclusions] Changes in the GS activity, GOGAT activity and soluble protein content in the flag leaf of foxtail millet varieties developed in recent years have a certain impact on yield. | Qinghua KONG Erying CHEN Shuting YU Yanbing YANG Ling QIN Feifei LI Yanan GUAN | 2019 | Agricultural Biotechnology2019，8，6： | 0 |
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