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Advances in the study of directed evolution for cellulases

Hailong LIN, Weiguang LI, Changhong GUO, Sihang QU, Nanqi REN

《环境科学与工程前沿（英文）》 2011年 第5卷 第4期   页码 519-525 doi: 10.1007/s11783-011-0326-2

摘要： If cellulose can be effectively hydrolyzed into glucose by cellulase, the production costs of hydrogen, ethanol or other chemicals from cellulosic materials will be greatly decreased, and economically viable production of biohydrogen and bioethanol will become feasible. Cellulose is degraded into glucoses by multi-component enzyme systems. Nowadays cellulases are widely used in brewing, food, bioenergy, fodder, textiles, paper, pharmaceuticals, environmental protection and other industries. However, existing cellulases have several problems that limit their wider applications, including the low turnover number for solid cellulosic materials, and low stability in adapting to various application conditions. For example, high temperature, low pH, and so on. Application of directed evolution technology may be one of the most effective ways for improving the characteristics of cellulases. This paper presents a brief review of the cellulose hydrolysis mechanism by cellulase, advances in cellulases (endoglucanase and -glucosidase) improvement by directed evolution for several characteristics (for instance, thermal stability, pH adaptability and enzyme activity), limitations of directed evolution for cellulases, and the outlook for directed evolution for cellulase.

关键词： biohydrogen     bioethanol     cellulase     cellulose     directed evolution    

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Development of a dual temperature control system for isoprene biosynthesis in

《化学科学与工程前沿（英文）》 2022年 第16卷 第7期   页码 1079-1089 doi: 10.1007/s11705-021-2088-0

摘要： Conflict between cell growth and product accumulation is frequently encountered in the biosynthesis of secondary metabolites. To address the growth-production conflict in yeast strains harboring the isoprene synthetic pathway in the mitochondria, the dynamic control of isoprene biosynthesis was explored. A dual temperature regulation system was developed through engineering and expression regulation of the transcriptional activator Gal4p. A cold-sensitive mutant, Gal4ep19, was created by directed evolution of Gal4p based on an internally developed growth-based high-throughput screening method and expressed under the heat-shock promoter PSSA4 to control the expression of PGAL-driven pathway genes in the mitochondria. Compared to the control strain with constitutively expressed wild-type Gal4p, the dual temperature regulation strategy led to 34.5% and 72% improvements in cell growth and isoprene production, respectively. This study reports the creation of the first cold-sensitive variants of Gal4p by directed evolution and provides a dual temperature control system for yeast engineering that may also be conducive to the biosynthesis of other high-value natural products.

关键词： transcriptional activator     directed evolution     dynamic control     heat-shock     isoprene    

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Unnormalized and normalized forms of gefura measures in directed and undirected networks

Raf GUNS,Ronald ROUSSEAU

《信息与电子工程前沿（英文）》 2015年 第16卷 第4期   页码 311-320 doi: 10.1631/FITEE.1400425

摘要： In some networks nodes belong to predefined groups (e.g., authors belong to institutions). Common network centrality measures do not take this structure into account. Gefura measures are designed as indicators of a node’s brokerage role between such groups. They are defined as variants of betweenness centrality and consider to what extent a node belongs to shortest paths between nodes from different groups. In this article we make the following new contributions to their study: (1) We systematically study unnormalized gefura measures and show that, next to the ‘structural’ normalization that has hitherto been applied, a ‘basic’ normalization procedure is possible. While the former normalizes at the level of groups, the latter normalizes at the level of nodes. (2) Treating undirected networks as equivalent to symmetric directed networks, we expand the definition of gefura measures to the directed case. (3) It is shown how Brandes’ algorithm for betweenness centrality can be adjusted to cover these cases.

关键词： Networks subdivided in groups     Partitions     Gefura measures     Q-measures     Brokerage role     Directed and undirected networks     Brandes’     algorithm    

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Controllability analysis of second-ordermulti-agent systemswith directed andweighted interconnection

Di GUO,Rong-hao ZHENG,Zhi-yun LIN,Gang-feng YAN

《信息与电子工程前沿（英文）》 2015年 第16卷 第10期   页码 838-847 doi: 10.1631/FITEE.1500069

摘要： This article investigates the controllability problem of multi-agent systems. Each agent is assumed to be governed by a second-order consensus control law corresponding to a directed and weighted graph. Two types of topology are considered. The first is concerned with directed trees, which represent the class of topology with minimum information exchange among all controllable topologies. A very simple necessary and sufficient condition regarding the weighting scheme is obtained for the controllability of double integrator multi-agent systems in this scenario. The second is concerned with a more general graph that can be reduced to a directed tree by contracting a cluster of nodes to a component. A similar necessary and sufficient condition is derived. Finally, several illustrative examples are provided to demonstrate the theoretical analysis results.

关键词： Multi-agent systems     Controllability     Directed tree    

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Ionic strength directed self-assembled polyelectrolyte single-bilayer membrane for low-pressure nanofiltration

《化学科学与工程前沿（英文）》 2022年 第16卷 第5期   页码 699-708 doi: 10.1007/s11705-021-2093-3

摘要： Layer-by-layer assembly is a versatile technique for fabricating nanofiltration membranes, where multiple layers of polyelectrolytes are usually required to achieve reasonable separation performance. In this work, an ionic strength directed self-assembly procedure is described for the preparation of nanofiltration membranes consisting of only a single bilayer of poly(diallyldimethylammoniumchloride) and poly(sodium-4-styrenesulfoate). The influence of background ionic strength as well as membrane substrate properties on the formation of single-bilayer membranes are systematically evaluated. Such a simplified polyelectrolyte deposition procedure results in membranes having outstanding separation performance with permeating flux of 14.2 ± 1.5 L∙m–2∙h–1∙bar–1 and Na2SO4 rejection of 97.1% ± 0.8% under a low applied pressure of 1 bar. These results surpass the ones for conventional multilayered polyelectrolyte membranes. This work encompasses an investigation of ionic strength induced coiling of the polyelectrolyte chains and emphasizes the interplay between-polyelectrolyte chain configuration and substrate pore profile. It thus introduces a new concept on the control of membrane fabrication process toward high performance nanofiltration.

关键词： layer-by-layer self-assembly     single bilayer     nanofiltration membrane     desalination    

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Liver-directed treatment is associated with improved survival and increased response to immune checkpoint

《医学前沿（英文）》   页码 878-888 doi: 10.1007/s11684-023-0993-y

摘要： Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词： uveal melanoma     liver-directed therapy     immune checkpoint blockade     SIRT     anti-PD-1     anti-CTLA-4    

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Clinical outcomes of ATP-tumor chemosensitivity assay directed chemotherapy in hepatocellular carcinoma

RAO Rongsheng, CHEN Wenxue, ZHOU Xinwen, ZHOU Zheng, LI Xiaojun, ZENG Zhiping

《医学前沿（英文）》 2007年 第1卷 第2期   页码 157-160 doi: 10.1007/s11684-007-0029-z

摘要： This study aims to investigate the clinical response of ATP tumor chemosensitivity assay (ATP-TCA) directed chemotherapy regimens delivered via hepatic artery infusion in 104 cases of primary liver carcinoma (PLC). Tumor tissue was obtained via laparotomy and cultivated in vitro. This tissue was put through the assay to determine chemosensitivity. A single drug regimen of either 5-FU, MMC and ADM and a combination drug regimen were used. The treatment assigned was dependent on the result of the ATP-TCA. In the control group, 30 cases of diagnosed PLC were given the conventional three-combination drug. The two groups were evaluated after three courses of chemotherapy. The results are as follows. The overall response rate of sensitivity test ranged from 36% to 44% in the single drug therapy groups and 81% in the combination drug group. The clinical overall response rate was 75% in the treatment group and 56% in control group. The treatment group had better results than the control group as survival period over six months was 80% and over one year 44%. In the control group, survival period over six months was 60% and 30% over one year. In short, ATP-TCA directed chemotherapy shows better results for terminal stages of PLC in that you can decrease the dose of drugs thereby reducing the side-effects with possible improvements in therapeutic effects.
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Site-directed mutagenesis of long QT syndrome KCNQ1 gene

LI Wei, WANG Bin, XU Qiumei, KE Qinmei, YANG Junguo, DU Rong, TIAN Li, WANG Qing

《医学前沿（英文）》 2008年 第2卷 第1期   页码 100-104 doi: 10.1007/s11684-008-0018-x

摘要： To construct a polymerase chain reaction (PCR) site-directed mutagenesis of the long QT syndrome KCNQ1 gene , two sets of primers were designed according to the sequence of KCNQ1 cDNA and a mismatch was introduced into primers. Mutagenesis was performed in a two-step PCR. The amplified fragments from the third PCR which contained the mutation site were sub-cloned into the T-vector pCR2.1. Then, the fragments containing the mutation site was obtained from pCR2.1 using restriction enzymes digestion and inserted into the same restriction site of pIRES-EGFP-KCNQ1. The sequencing analysis shows that the mutation site was correct. Mutation from A to G in site 983 of KCNQ1 cDNA was found. Using the Effectene transfection reagent, pIRES-EGFP-KCNQ1 (G983A) was transfected into HEK cells successfully. These results may shed light on further functional study of KCNQ1 gene.

关键词： restriction     digestion     syndrome     sequence     site-directed mutagenesis    

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oocyst directed assembly of gold nanoparticles and graphene oxide

Sona Jain, Zhicheng Huang, Brent R. Dixon, Syed Sattar, Juewen Liu

《化学科学与工程前沿（英文）》 2019年 第13卷 第3期   页码 608-615 doi: 10.1007/s11705-019-1813-4

摘要： Understanding the interactions between inorganic nanomaterials and biological species is an important topic for surface and environmental chemistry. In this work, we systematically studied the oocysts of as a model protozoan parasite and its interaction with gold nanoparticles (AuNPs) and graphene oxide (GO). The as-prepared citrate-capped AuNPs adsorb strongly on the oocysts leading to a vivid color change. The adsorption of the AuNPs was confirmed by transmission electron microscopy. Heat treatment fully inhibited the color change, indicating a large change of surface chemistry of the oocysts that can be probed by the AuNPs. Adding proteases such as trypsin and proteinase K partially inhibited the color change. DNA-capped AuNPs, on the other hand, could not be adsorbed by the oocysts. GO was found to wrap around the oocysts forming a conformal shell reflecting the shape of the oocysts. Both citrate-capped AuNPs and GO compromised the membrane integrity of the oocysts as indicated by the propidium iodide staining experiment, and they may be potentially used for inactivating the oocysts. This is the first example of using nanomaterials to probe the surface of the oocysts, and it suggests the possibility of using such organisms to template the assembly of nanomaterials.

关键词： nanomaterials     toxicology     water     biosensors    

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Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 90-99 doi: 10.1007/s11684-015-0390-2

摘要：

Gene therapy provides a potential cure for hemophilia B, and significant progress has been achieved in liver-directed gene transfer mediated by adeno-associated viral vectors. Recent clinical trials involving the use of a self-complementary adeno-associated virus serotype 8-human codon-optimized factor IX (AAV8-hFIXco) vector demonstrated encouraging efficacy with hFIX expression stabilized at 1% to 6% of normal level in patients, but safety concerns related to high vector doses are still present. Thus, further improvement of AAV vectors and hFIX expression cassette may positively contribute to the ultimate success of hemophilia B gene therapy. In this study, to obtain a higher expression level of hFIX that potentiates the coagulant capacity of recipients, human FIX expression vector was optimized by upgrading the codon adaption index and adjusting the GC content, inserting a Kozak sequence (GCCACC), and introducing a gain-of-function mutation, R338L (FIX Padua). The efficiency of the published and the presently constructed cassettes was compared through in vivo screening. In addition, the regulatory elements that control the FIX gene expression in these cassettes were screened for liver-specific effectiveness. Among all the constructed cassettes, scAAV-Pre-hFIXco-SIH-R338L, which was the construct under the control of the prothrombin enhancer and prealbumin promoter, resulted in the highest level of coagulant activity, and the expression levels of two constructed cassettes (scAAV-Chi-hFIXco-SIH-R338L and scAAV-Pre-hFIXco-SIH-R338L) were also higher than that of the published cassette (scAAV-LP1-hFIXco-SJ). In summary, our strategies led to a substantial increase in hFIX expression at the protein level or a remarkably elevated coagulant activity. Thus, these reconstructs of hFIX with AAV vector may potentially contribute to the creation of an efficacious gene therapy of hemophilia B.

关键词： factor IX     hemophilia B     liver-specific regulatory elements     hydrodynamic gene transfer    

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Tuned reactive power dispatch through modified differential evolution technique

S. BISWAS (RAHA), N. CHAKRABORTY

《能源前沿（英文）》 2012年 第6卷 第2期   页码 138-147 doi: 10.1007/s11708-012-0188-8

摘要： This paper explores the capability of modified differential evolution (MDE) technique for solving the reactive power dispatch (RPD) problem. The proposed method is based on the basic differential evolution (DE) technique with a few modifications made into it. DE is one of the strongest optimization techniques though it suffers from the problem of slow convergence while global minima appear. The proposed modifications are tried to resolve the problem. The RPD problem mainly defines loss minimization with stable voltage profile. To solve the RPD problem, the generator bus voltage, transformer tap setting and shunt capacitor placements are controlled by the MDE approach. In this paper, IEEE 14-bus and IEEE 30-bus systems are chosen for MDE implementation. The applied modification show much improved result in comparison to normal DE technique. Comparative study with other soft-computing technique including DE validates the effectiveness of the proposed method.

关键词： reactive power dispatch (RPD)     modified differential evolution (MDE)     differential evolution algorithm with localizations around the best vector (DELB)    

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Strategic Thinking on a Revolution/an Evolution in Production and Consumption of Energy in China

Ke-chang Xie,Ke Liu

《工程管理前沿（英文）》 2014年 第1卷 第1期   页码 30-36 doi: 10.15302/J-FEM-2014006

摘要： This article summarizes the thinking behind the call for a revolution/an evolution in China's energy production and consumption. China is still a developing country, though it has experienced fast economic growth in the past thirty years. It achieved great accomplishments surprising the world, and it is also confronted with challenges on energy supply and environmental protection. As environmental pollution becomes more and more serious, the energy challenges have become more and more complicated. With this in mind, the authors analyzed China's energy situation, China's energy supply and consumption, the world energy map, China's commitment both to improving its domestic environment and fulfilling its international obligations to control climate change. Action plans are presented to support the call for a revolution/an evolution in China's energy production and consumption as an effective assurance for China's ambitious goal of building a moderately prosperous society in all respects.

关键词： revolution     evolution     energy     production     consumption    

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Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 354-364 doi: 10.1007/s11684-018-0665-5

摘要： The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon- (IFN- ) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied ( =47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms’ tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% ( =0.377) and 9.1% and 0.0% ( =0.985) for patients in the IFN- and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% ( =0.891) and 84.3% and 84.6% ( =0.972) for patients in the IFN- and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN- treatment.

关键词： donor leukocyte infusion     hematopoietic stem cell transplantation     interferon-   

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Polypyrrole@NiCo hybrid nanotube arrays as high performance electrocatalyst for hydrogen evolution reaction

Shenghua Ye, Gaoren Li

《化学科学与工程前沿（英文）》 2018年 第12卷 第3期   页码 473-480 doi: 10.1007/s11705-018-1724-9

摘要：

The polypyrrole(PPy)@NiCo hybrid nanotube arrays have been successfully fabricated as a high performance electrocatalyst for hydrogen evolution reaction (HER) in alkaline solution. The strong electronic interactions between PPy and NiCo alloy are confirmed by X-ray photoelectron spectroscopy and Raman spectra. Because these interations can remarkably reduce the apparent activation energy (Ea) for HER and enhance the turnover frequency of catalysts, the electrocatalytic performance of PPy@NiCo hybrid nanotube arrays are significantly improved. The electrochemical tests show that the PPy@NiCo hybrid catalysts exhibit a low overpotential of ~186 mV at 10.0 mA·cm−2 and a small tafel slope of 88.6 mV·deg−1 for HER in the alkaline solution. The PPy@NiCo hybrid nanotubes also exhibit high catalytic activity and high stability for HER.

关键词： NiCo alloy     polypyrrole     hybrid nanotube     electrocatalyst     hydrogen evolution reaction    

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Synergistic effect of V and Fe in Ni/Fe/V ternary layered double hydroxides for efficient and durable oxygen evolution

《化学科学与工程前沿（英文）》 2023年 第17卷 第1期   页码 102-115 doi: 10.1007/s11705-022-2179-6

摘要： High-performance and stable electrocatalysts are vital for the oxygen evolution reaction (OER). Herein, via a one-pot hydrothermal method, Ni/Fe/V ternary layered double hydroxides (NiFeV-LDH) derived from Ni foam are fabricated to work as highly active and durable electrocatalysts for OER. By changing the feeding ratio of Fe and V salts, the prepared ternary hydroxides were optimized. At an Fe:V ratio of 0.5:0.5, NiFeV-LDH exhibits outstanding OER activity superior to that of the binary hydroxides, requiring overpotentials of 269 and 274 mV at 50 mA·cm–2 in the linear sweep voltammetry and sampled current voltammetry measurements, respectively. Importantly, NiFeV-LDH shows extraordinary long-term stability (≥ 75 h) at an extremely high current density of 200 mA·cm–2. In contrast, the binary hydroxides present quick decay at 200 mA·cm–2 or even reduced current densities (150 and 100 mA·cm–2). The outstanding OER performance of NiFeV-LDH benefits from the synergistic effect of V and Fe while doping the third metal into bimetallic hydroxide layers: (a) Fe plays a crucial role as the active site; (b) electron-withdrawing V stabilizes the high valence state of Fe, thus accelerating the OER process; (c) V further offers great stabilization for the formed intermediate of FeOOH, thus achieving superior durability.

关键词： oxygen evolution reaction     electrocatalysts     ternary layered double hydroxides     long-term stability    

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标题 作者 时间 类型 操作

Advances in the study of directed evolution for cellulases

Hailong LIN, Weiguang LI, Changhong GUO, Sihang QU, Nanqi REN

期刊论文

Development of a dual temperature control system for isoprene biosynthesis in

期刊论文

Unnormalized and normalized forms of gefura measures in directed and undirected networks

Raf GUNS,Ronald ROUSSEAU

期刊论文

Controllability analysis of second-ordermulti-agent systemswith directed andweighted interconnection

Di GUO,Rong-hao ZHENG,Zhi-yun LIN,Gang-feng YAN

期刊论文

Ionic strength directed self-assembled polyelectrolyte single-bilayer membrane for low-pressure nanofiltration

期刊论文

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint

期刊论文

Clinical outcomes of ATP-tumor chemosensitivity assay directed chemotherapy in hepatocellular carcinoma

RAO Rongsheng, CHEN Wenxue, ZHOU Xinwen, ZHOU Zheng, LI Xiaojun, ZENG Zhiping

期刊论文

Site-directed mutagenesis of long QT syndrome KCNQ1 gene

LI Wei, WANG Bin, XU Qiumei, KE Qinmei, YANG Junguo, DU Rong, TIAN Li, WANG Qing

期刊论文

oocyst directed assembly of gold nanoparticles and graphene oxide

Sona Jain, Zhicheng Huang, Brent R. Dixon, Syed Sattar, Juewen Liu

期刊论文

Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B

null

期刊论文

Tuned reactive power dispatch through modified differential evolution technique

S. BISWAS (RAHA), N. CHAKRABORTY

期刊论文

Strategic Thinking on a Revolution/an Evolution in Production and Consumption of Energy in China

Ke-chang Xie,Ke Liu

期刊论文

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

期刊论文

Polypyrrole@NiCo hybrid nanotube arrays as high performance electrocatalyst for hydrogen evolution reaction

Shenghua Ye, Gaoren Li

期刊论文

Synergistic effect of V and Fe in Ni/Fe/V ternary layered double hydroxides for efficient and durable oxygen evolution

期刊论文