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| 1 | Metabolic engineering and flux analysis of Corynebacterium glutamicum for L-serine production显示文摘L-Serine plays a critical role as a building block for cell growth, and thus it is difficult to achieve the direct fermentation of L-serine from glucose. In this study, Corynebacterium glutamicum ATCC 13032 was engineered de novo by blocking and attenuating the conversion of L-serine to pyruvate and glycine, releasing the feedback inhibition by L-serine to 3-phosphoglycerate dehydrogenase (PGDH), in combination with the co-expression of 3-phosphoglycerate kinase (PGK) and feedback-resistant PGDH (PGDHr). The resulting strain, SER-8, exhibited a lower specific growth rate and significant differences in L-serine levels from Phase I to Phase V as determined for fed-batch fermentation. The intracellular L-serine pool reached (14.22±1.41) μmol gCDM 1, which was higher than glycine pool, contrary to fermentation with the wild-type strain. Furthermore, metabolic flux analysis demonstrated that the over-expression of PGK directed the flux of the pentose phosphate pathway (PPP) towards the glycolysis pathway (EMP), and the expression of PGDHr improved the L-serine biosynthesis pathway. In addition, the flux from L-serine to glycine dropped by 24%, indicating that the deletion of the activator GlyR resulted in down-regulation of serine hydroxymethyltransferase (SHMT) expression. Taken together, our findings imply that L-serine pool management is fundamental for sustaining the viability of C. glutamicum, and improvement of C1 units generation by introducing the glycine cleavage system (GCV) to degrade the excessive glycine is a promising target for L-serine production in C. glutamicum. | LAI ShuJuan ZHANG Yun LIU ShuWen LIANG Yong SHANG XiuLing CHAI Xin WEN TingYi | 2012 | Science China(Life Sciences)2012，55，4： | 15 |
| 2 | New ancient DNA sequences suggest high genetic diversity for the woolly mammoth (Mammuthus primigenius)显示文摘细胞色素 b 基因(mtDNA ) 的部分 DNA 序列成功地从从 Xiguitu 县(Yakeshi ) 收集的 Mammuthus primigenius 的迟了的更新世石块骨头被检索,内部蒙古自治区域并且从 Zhaodong,在北中国的 Heilongjiang 省的哈尔滨。二古老的 DNA 碎片(109 bp 和 124 bp ) 被可再现的实验与另外的 Elephantidae 税在二个不同实验室并且由种系发生的分析证实一。用在分开或联合的数据集的这些序列和出版数据的种系发生的分析在毛茸茸的猛犸和二头生活大象之中显示不稳定的关系, Elephas 和 Laxodonta。除了过去常尝试 Elephantidae 终端的长独立的进化的短序列征税一,我们建议高 intra 特定的差异在 Mammuthus primigeniuscrossing 存在空间、时间的范围,为 DNA 导致建筑群和分叉的基因背景到目前为止定序恢复。在绝灭的毛茸茸的猛犸的高基因的差异能解释 Elephantidae 税的明显的不稳定性一上分子的种系发生的树和罐头关于未解决的 Elephantidae 三分法调解明显的悖论。 | YANG Shujuan LAI Xulong SHI Suhua CHENG Shenghong ZHOU Xiugao YANG Xiujuan YANG Hong | 2006 | Progress in Natural Science:Materials International2006，16，4： | 5 |
| 3 | Forecast analysis of the refreezing of Kunlun mountain permafrost tunnel on Qing–Tibet railway in China显示文摘 | Zhang Xuefu Lai Yuanming Yu Wenbing Zhang Shujuan Xiao Jianzhang | 2004 | Cold Regions Science and Technology2004，，1： | 1 |
| 4 | Study on the damage propagation of surrounding rock from a cold region tunnel under freeze-thaw cycle condition显示文摘 | Zhang Shujuan Lai Yuanming Zhang Xuefu | 2004 | Tunneling and Underground Space Technology2004，19，3： | 1 |
| 5 | Three-dimensional nonlinear analysis for the coupled problem of the heat transfer of the surrounding rock and the heat convection between the air and the surrounding rock in cold-region tunnel显示文摘 | Lai Yuanming Zhang Xuefu Yu Wenbing Zhang Shujuan Liu Zhiqiang Xiao Jianzhang | 2005 | Tunnelling and Underground Space Technology incorporating Trenchless Technology Research2005，，4： | 1 |
| 6 | Study on the damage propagation of surrounding rock from a cold-region tunnel under freeze–thaw cycle condition显示文摘 | Shujuan Zhang Yuanming Lai Xuefu Zhang Yibin Pu Wenbin Yu | 2003 | Tunnelling and Underground Space Technology incorporating Trenchless Technology Research2003，，3： | 1 |
| 7 | Adjusting temperature distribution under the south and north slopes of embankment in permafrost regions by the ripped-rock revetment显示文摘 | Yuanming Lai Shujuan Zhang Luxin Zhang etal | 2004 | Cold Regions Science and Technology2004，39，： | 1 |
| 8 | An Improved Statistical Damage Constitutive Model forWarm Frozen Clay Based on Mohr-Coulomb Criterion 显示文摘 | LI Shuangyang LAI Yuanming ZHANG Shujuan | 2008 | Cold Regions Science and Technology2008，57，23： | 1 |
| 9 | Adjusting temperature distribution under the south and north slopes of embankment in permafrost regions by the riprap-rock revetment 显示文摘 | Lai Yuanming Zhang Shujuan Zhang Luxin | 2004 | Cold Regions Science and Technology2004，39，： | 1 |
| 10 | An Old Story Retold: Loss of G1 Control Defines A Distinct Genomic Subtype of Esophageal Squamous Cell Carcinoma显示文摘Esophageal squamous cell carcinoma(ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration(CNA) and loss of heterozygosity(LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations(NSSMs) in102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology(GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B(30.9%), amplification of 11q13.3 covering CCND1(30.9%), and TP53 point mutation(50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC.Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes.These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting. | Qiyan Wang Jian Bai Amir Abliz Ying Liu Kenan Gong Jingjing Li Wenjie Shi Yaqi Pan Fangfang Liu Shujuan Lai Haijun Yang Changdong Lu Lixin Zhang Wei Chen Ruiping Xu Hong Cai Yang Ke Changqing Zeng | 2015 | Genomics, Proteomics & Bioinformatics2015，13，4： | 1 |
| 11 | Study on the damage propagation of surrounding rock from a cold-region tunnel under freeze–thaw cycle condition显示文摘 | Shujuan Zhang Yuanming Lai Xuefu Zhang Yibin Pu Wenbin Yu | 2003 | Tunnelling and Underground Space Technology incorporating Trenchless Technology Research2003，，3： | 1 |
| 12 | The binding epitope of sintilimab on PD-1 revealed by AbMap显示文摘PD-1 plays an important role as an immune checkpoint.Sintilimab is a newly approved PD-1 antibody for cancer immunotherapy with an unknown binding epitope on PD-1.In this study,to elucidate the molecular mechanism by which sintilimab blocks PD-1 activation,we applied Antibody binding epitope Mapping(AbMap)to identify the binding epitope of sintilimab.An epitope was successfully identified,i.e.SLAPKA,aa 127-132.By constructing a series of point mutations,the dominant residues S127,L128,A129,P130,and A132 of PD-1 were further validated by western blot analysis,biolayer interferometry,and flow cytometry.Structural analysis showed that the epitope is partially within the binding interface of PD-1 and PD-L1,and this epitope also partially overlaps with that of nivolumab and pembrolizumab.These results demonstrate that sintilimab can attenuate PD-1 activation by directly competing with the interaction between PD-1 and PD-L1 through binding with the key residues of the FG loop on PD-1.This study also demonstrates the high efficiency and accuracy of AbMap for determining the binding epitope of therapeutic antibodies. | Mingliang Ma Huan Qi Chuansheng Hu Zhaowei Xu Fanlin Wu Nan Wang Danyun Lai Yang Li Hainan Zhang Hewei Jiang Qingfeng Meng Shujuan Guo Yani Kang Xiaodong Zhao Hua Li Sheng-ce Tao | 2021 | Acta Biochimica et Biophysica Sinica2021，53，5： | 1 |
| 13 | An im- proved statistical damage constitutive model for warm frozen clay based on Mohr Coulomb criterion显示文摘 | Li Shuangyang Lai Yuanming Zhang Shujuan | 2009 | Cold Regions Sci- ence and Technology2009，57，： | 1 |
| 14 | Adjusting temperature distribution under the south and north slopes of embankment in permafrost regions by the ripped-rock revetment显示文摘 | Lai Yuanming Zhang Shujuan Zhang Luxin | 2004 | Cold Regions Science and Technology2004，39，： | 1 |
| 15 | Study of Methods to Control Frost Action in Cold Regions Tunnels 显示文摘 | LAI Yuanming WU Ziwang ZHANG Shujuan | 2003 | Journal of Cold Regions Engineering2003，17，4： | 1 |
| 16 | Volumetric strain and strength behavior of frozen soils under confinement显示文摘 | Zhang Shujuan Lai Yuanming Sun Zhizhong | 2007 | Cold Regions Science and Technology2007，47，3： | 1 |
| 17 | Experimental studies on the ripped-rock revetment embankment in permafrost regions of the Qinghai-Tibet railroad显示文摘 | Yu Wenbing Lai Yuanming Zhang Shujuan | 2006 | Cold Regions Science and Technology2006，45，： | 1 |
| 18 | Non-linear Analysis for the Freezing-thawing Situation of the Rock Surrounding the Tunnel in Cold Regions under the Conditions of Different Construction Seasons, Initial Temperatures and Insulations 显示文摘 | Zhang Xuefu Lai Yuanming Yu Wenbing Zhang Shujuan | 2002 | Tunnelling and Underground Space Technology2002，17，3： | 1 |
| 19 | Nonlinear Analysis for the Three-dimensional Temperature Fields in Cold Regions Tunnels 显示文摘 | Zhang Xuefu Lai Yuanming Yu Wenbing Zhang Shujuan | 2002 | Cold Regions Science and Technology2002，35，3： | 1 |
| 20 | Adjusting Temperature Distribution under the South and North slopes of Embankment in Permafrost Regions by the Ripped-rock embankment显示文摘 | Lai Yuanming Zhang Shujuan Zhang Luxin | 2004 | Cold Regions Science and Technology2004，39，1： | 1 |
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