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Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

《医学前沿（英文）》 2023年 第17卷 第3期   页码 493-502 doi: 10.1007/s11684-022-0946-x

摘要： Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

关键词： ALK fusion     next-generation sequencing     fluorescence in situ hybridization     immunohistochemistry     variant allele frequency     intratumoral heterogeneity     targeted therapy    

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基于荧光原位杂交技术的UASB颗粒污泥中苯酚降解微生物生态位分化研究 Article

Kengo Kubota, Kei Igarashi, Masayoshi Yamada, Yasuyuki Takemura, Yu-You Li, Hideki Harada

《工程（英文）》 2022年 第9卷 第2期   页码 61-66 doi: 10.1016/j.eng.2021.05.012

摘要：

利用荧光原位杂交（FISH）和克隆文库构建技术，研究了厌氧污泥床反应器处理含酚废水时所收获的颗粒的微生物群落结构。研究发现，互营杆菌（Syntrophorhabdaceae）和隐杆厌氧菌（Cryptanaerobacter）的克隆是苯酚降解的主要原因。为了准确地对隐杆厌氧菌的克隆进行分类归属，需要利用近全长的16S核糖体RNA（rRNA）基因序列进行进化分析。设计了三种寡核苷酸探针用于检测以下三个分类群：互营杆菌、隐杆厌氧菌和互养菌。对厌氧颗粒薄片的FISH 分析显示细菌和古菌呈随机分布。然而，互营杆菌、隐杆厌氧菌和互养菌分布明确。在颗粒细胞的外层发现了隐杆厌氧菌和互养菌，两者关系密切，而互营杆菌则位于颗粒细胞的深层。细菌之间的代谢联系和对底物的亲和力很可能是造成这种特殊分布的原因。研究人员观察到颗粒污泥中苯酚的降解主要通过以下方式进行：首先，隐杆厌氧菌将苯酚转化为苯甲酸盐，然后被互养菌降解为乙酸盐。苯酚的这种互饲降解发生在颗粒表面附近，此处苯酚浓度较高。在苯酚浓度较低的颗粒深部，互营杆菌将苯酚降解为乙酸盐。结果表明，互营杆菌不太可能产生苯甲酸盐，并将其作为中间产物来喂养邻近的生物，这一点与以往研究所提出的理论相矛盾。

关键词： 隐杆厌氧菌（Cryptanaerobacter）     荧光原位杂交     苯酚厌氧降解     互营杆菌（Syntrophorhabdaceae）     互养菌（Syntrophus）     升流式厌氧污泥床（UASB）颗粒污泥    

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Short-term effects of excessive anaerobic reaction time on anaerobic metabolism of denitrifying polyphosphate- accumulating organisms linked to phosphorus removal and N

Gang GUO, Yayi WANG, Chong WANG, Hong WANG, Mianli PAN, Shaowei CHEN

《环境科学与工程前沿（英文）》 2013年 第7卷 第4期   页码 616-624 doi: 10.1007/s11783-013-0505-4

摘要： The short-term effect of anaerobic reaction time (AnRT) (i.e., 90, 120 and 150 min) on the denitrifying phosphorus (P) removal performance and N O production was examined using a denitrifying enhanced biologic phosphorus removal (EBPR) sludge acclimatized with mixed acetate (HAc) and propionate (Pro) (in the molar ratio 3∶1) as carbon sources. The results showed that when the AnRT was prolonged from 90 to 150 min, the anaerobic polyhydroxyalkanoate (PHA) synthesis was decreased by 15.3%. Moreover, the ineffective PHA consumption occurred in anaerobic phases and contributed to an increased accumulation and higher free nitrous acid (FNA) concentrations (≥0.001–0.0011 mg HNO -N/L) in the subsequent anoxic phases, causing a severe inhibition on anoxic P-uptake and denitrification. Accordingly, the total nitrogen (TN) and total phosphorus (TP) removal efficiencies dropped by approximately 6.3% and 85.5%, respectively; and the ratio of anoxic N O-N production to TN removal increased by approximately 3.8%. The fluorescence in situ hybridization (FISH) analysis revealed that the sludge was mainly dominated by (62.0% (SE = 1.5%)). In conclusion, the short-term excessive anaerobic reaction time negatively impacted denitrifying P removal performance and stimulated more N O production, and its effect on P removal was more obvious than that on nitrogen removal.

关键词： Denitrifying phosphorus removal     anaerobic reaction time     nitrous oxide     polyhydroxyalkanoate     free nitrous acid     fluorescence in-situ hybridization    

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hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 92-102 doi: 10.1007/s11705-021-2063-9

摘要： Mitochondrial DNA has a special structure that is prone to damage resulting in many serious diseases, such as genetic diseases and cancers. Therefore, the rapid and specific monitoring of mitochondrial DNA damage is urgently needed for biological recognition. Herein, we constructed an in situ hydrophobic environment-triggering reactive fluorescence probe named MBI-CN. The fluorophore was 2-styrene-1H-benzo[d]imidazole, and malononitrile was introduced as a core into a molecule to initiate the hydrolysis reaction in the specific environment containing damaged mitochondrial DNA. In this design, MBI-CN conjugates to mitochondrial DNA without causing additional damages. Thus, MBI-CN can be hydrolyzed to generate MBI-CHO in an in situ hydrophobic environment with mitochondrial DNA damage. Meanwhile, MBI-CHO immediately emitted a significative fluorescence signal changes at 437 and 553 nm within 25 s for the damaged mitochondria DNA. Give that the specific and rapid response of MBI-CN does not cause additional damages to mitochondrial DNA, it is a potentially effective detection tool for the real-time monitoring of mitochondrial DNA damage during cell apoptosis and initial assessment of cell apoptosis.

关键词： hydrolysis reaction     mitochondrial DNA damage     in situ hydrophobic environment trigger     fluorescence probe     apoptosis    

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Short-term effect of temperature variation on the competition between PAOs and GAOs during acclimation period of an EBPR system

Nanqi REN, Han KANG, Xiuheng WANG, Nan LI

《环境科学与工程前沿（英文）》 2011年 第5卷 第2期   页码 277-282 doi: 10.1007/s11783-010-0226-x

摘要： Sequencing batch reactor (SBR) for enhanced biological phosphorus removal (EBPR) processes was used to investigate the impact of the temperature shock on the competition between phosphorus-accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) in start-up stage. During the 34 days operation, SBR was set with temperature variation(0–5 d, 22±1°C; 6–13 d, 29±1°C; 14–34 d, 14±1°C). PAOs and GAOs were analyzed by fluorescent in situ hybridization (FISH), and intracellular polyphosphate granules were stained by Neisser-stain. The results showed that the influence of temperature shock on PAOs’ abundance was more serious than that on GAOs in the enriching process. Under sudden and substantially temperature variation, from 22±1°C to 29±1°C and then to 14±1°C, the domination of PAOs was deteriorated. After temperature shock, PAOs’ competitive advantages at low temperature that concluded in other study did not appear in our study. As mesophilic, GAOs (indicated by and ) were more temperature adaptive and better grew and took the domination at 14±1°C in the end. In the competition process, organisms of tetrad forming organisms (TFOs)-like shape which were considered as typical GAOs, were observed. With the evidence of poly-P granules containing by Neisser-straining and result of FISH, these organisms of TFOs-like shape were better to be assumed as adaption state or a special self-protecting shape of PAOs.

关键词： fluorescent in situ hybridization (FISH)     tetrad forming organisms (TFOs)     temperature variation     enhanced biological phosphorus removal (EBPR)    

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Comments on “Determination of heterozygosity for avirulence/virulence loci through sexual hybridization

Ralf T. Voegele

《农业科学与工程前沿（英文）》 2017年 第4卷 第1期   页码 121-122 doi: 10.15302/J-FASE-2017142

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Determination of heterozygosity for avirulence/virulence loci through sexual hybridization of

Yuan TIAN,Gangming ZHAN,Xia LU,Jie ZHAO,Lili HUANG,Zhensheng KANG

《农业科学与工程前沿（英文）》 2017年 第4卷 第1期   页码 48-58 doi: 10.15302/J-FASE-2016114

摘要： Wheat stripe rust caused by f. sp. is one of the most devastating diseases of wheat worldwide and resistant cultivars are vital for its management. Therefore, investigating the heterozygosity of the pathogen is important because of rapid virulence changes in isolates heterozygous for avirulence/virulence. An isolate of f. sp. was selfed on to determine the heterozygosity for avirulence/virulence loci. One hundred and twenty progeny isolates obtained from this selfing were phenotyped using 25 lines of wheat containing genes and genotyped with 96 simple sequencing repeat markers, with 51 pathotypes and 55 multi-locus genotypes being identified. All of these were avirulent on lines with , , , and and virulent on lines with , and , indicating that the parental isolate was homozygously avirulent or homozygously virulent for these loci. Segregation was found for wheat lines with , , , , , , , , , , , , , , , and . The 17 cultivars to which the was identified as heterozygous with respect to virulence/avirulence should not be given priority in breeding programs to obtain new resistant cultivars.

关键词： Puccinia striiformis f. sp. tritici     selfing     heterozygosity     virulence inheritance    

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Effect of fiber hybridization on energy absorption and synergy in concrete

Ahmadreza RAMEZANI, Mohammad Reza ESFAHANI

《结构与土木工程前沿（英文）》 2019年 第13卷 第6期   页码 1338-1349 doi: 10.1007/s17009-019-0558-2

摘要： In the present study, steel and polypropylene (PP) fibers have been utilized with the intent of obtaining hybrid fiber-reinforced concrete (HFRC) with desirable mechanical properties. An attempt has been made to scrutinize the properties of HFRC with the main concentration being on energy absorption characteristics of concrete and the efficacy of fiber hybridization in producing synergy. Accordingly, a total of 180 specimens, representing 20 different mixtures have been cast and evaluated through compressive, split tensile, and flexural tests. The relevant flexural toughness of the specimens was calculated using ASTM C1018, ASTM C1609, JSCE, and PCS methods, and the effectiveness of these methods was evaluated based on the experimental results. It was observed that steel fibers are more effective in the improvement of flexural toughness in the presence of PP fibers. Furthermore, synergy associated with the combination of fibers at different stages of deflection of the beam specimens was observed and analyzed.

关键词： hybrid fiber-reinforced concrete     synergy     toughness     steel fibers     polypropylene fibers    

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Development and application of ex-situ presulfurization technology for hydrotreating catalysts in China

Yulan GAO, Xiangchen FANG, Zhenmin CHENG

《化学科学与工程前沿（英文）》 2011年 第5卷 第3期   页码 287-296 doi: 10.1007/s11705-010-0529-2

摘要： The development and application of ex-situ presulfurization (EPRES) technology for hydrotreating catalysts has been reviewed in the present article. The studies in laboratory scale and commercial practice indicated that the adoption of the EPRES catalyst in industrial application can significantly enhance the degree of presulfurization of metal oxide components, shorten the start-up period, and effectively reduce the environmental impact as well as the danger of start-up procedure in industrial hydrotreating unit. This catalyst has been proved to be versatile for different types of hydrogenation reactions. Different types of active site models are also discussed for better understanding the nature of presulfurized catalysts.

关键词： ex-situ presulfurization     in situ presulfurization     hydrotreating catalyst     sulfur utilization ratio    

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Synthesis and fluorescence behavior of 2,5-diphenyl-1,3,4-oxadiazole-containing bismaleimides and bissuccinimides

Xin ZHANG, Zichen LI

《化学科学与工程前沿（英文）》 2013年 第7卷 第4期   页码 381-387 doi: 10.1007/s11705-013-1359-9

摘要： Bismaleimides bearing 2,5-diphenyl-1,3,4-oxadiazole chromophores at , , position and corresponding saturated bissuccinimides were synthesized. Several synthetic strategies for these bismaleimides were discussed in detail. Almost no or very weak fluorescence was observed for these bismaleimides, however, the bissuccinimides show a strong fluorescence. The effect of molecular geometry on optical behavior and fluorescence quenching mechanism were investigated by UV-vis absorption and fluorescence emission spectroscopy. The electron coupling of ground state of -bismaleimide is stronger than those of - and -bismaleimides. -Bissuccinimide displays increasing fluorescence quantum yields with red shifts of 22–24 nm, compared to -bissuccinimide. Polymerizable C=C bonds play a key role in the intramolecular fluorescence quenching.

关键词： fluorescence     bismaleimide     oxadiazole     succinimide    

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Polyolefin-nanocomposites with special properties by in-situ polymerization

Walter Kaminsky

《化学科学与工程前沿（英文）》 2018年 第12卷 第3期   页码 555-563 doi: 10.1007/s11705-018-1715-x

摘要：

Exceptionally strong polyolefin nanocomposites are synthesized by in-situ polymerization using soluble metallocene/methylaluminoxane (MAO) as catalysts in a two-step process. First, the soluble metallocene/MAO or other single site catalysts are absorbed on the surface of the nanofillers. Then by addition of ethene or propene, a polyolefin film is formed, covering the nanoparticles, layered silicates, or fibers. The resulting polyethylene and polypropylene nanocomposites are characterized by better physical and chemical properties such as stiffness, gas barrier properties, degradation temperatures, and crystallization rates. They show better mechanical properties than materials produced by mechanical blending. The thickness of the polyolefin can be controlled by the pressure of ethene or propene and by the polymerization time. Carbon fibers and carbon nanotubes are covered with isotactic or syndiotactic polypropylene. Because of the hydrophobic character of the carbon surface, the polymer is drawn on the fiber. This leads to a reinforced combined polymer with special properties. The crystallization temperature is 10 °C higher and therefore the crystallization rate up to 20 times faster than that of pure syndiotactic polypropylene. The form stability increases by 100% if 3 wt-% of carbon nanotubes are incorporated.

关键词： polyolefin nanocomposites     metallocenes     methylaluminoxane    

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Synthesis and characterization of 2,5-bis[4-(2-arylvinyl)phenyl]-1,3,4-oxadiazoles with two-photon fluorescence

ZHU Xiaoqin, QIAN Ying, LU Zhifeng

《化学科学与工程前沿（英文）》 2007年 第1卷 第4期   页码 381-384 doi: 10.1007/s11705-007-0069-6

摘要： Four novel 2,5-bis[4-(2-arylvinyl)phenyl]-1,3,4-oxadiazoles that exhibit strong two-photon absorption and enhanced two-photon excited fluorescence were designed and synthesized based on push-core-pull-core-push molecules built from embedding electron-transporting 1,3,4-oxadiazole in aromatic conjugated system through Wittig-Horner reaction. Their chemical structures were determined to show trans-vinylene character according to infrared (IR) and H nuclear magnetic resonance (NMR) spectra. A very effective energy transfer from the excited units to the ?-conjugated bridging unit can enhance the two-photon absorption and two-photon fluorescence.

关键词： 2-arylvinyl     trans-vinylene character     effective     fluorescence     push-core-pull-core-push    

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Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

《化学科学与工程前沿（英文）》 2023年 第17卷 第3期   页码 298-306 doi: 10.1007/s11705-022-2212-9

摘要： Herein, a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method. The carbon dots-based sensor (CA-CDs) exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00. Notably, the fluorescence sensor has a reversible response to pH change. Finally, the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice. Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice, while the pH value in liver of diabetic mice was almost the same as that of the normal mice. The present study provides a simple analytical method for pH detection suitable for in vivo.

关键词： carbon dots     two-photon imaging     pH     diabetic mice    

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Insight into fluorescence properties of 14 selected toxic single-ring aromatic compounds in water: Experimental

Muhammad Farooq Saleem Khan, Jing Wu, Cheng Cheng, Mona Akbar, Chuanyang Liu, Bo Liu, Jian Shen, Yu Xin

《环境科学与工程前沿（英文）》 2020年 第14卷 第3期 doi: 10.1007/s11783-020-1219-z

摘要： The fluorescence peak location of 14 compounds interpreted at protein-like region. The p-electron system inside aromatic ring contributes to the fluorophore region. Functional group variation effects the emission spectra. Decrease in quantum yield and increase in DE is due to atomic weight F>Cl>Br>I. Theoretically results are in line with experimental ones. Various single-ring aromatic compounds in water sources are of great concern due to its hazardous impact on the environment and human health. The fluorescence excitation-emission matrix (EEMs) spectrophotometry is a useful method to identify organic pollutants in water. This study provides a detailed insight into the fluorescence properties of the 14 selected toxic single-ring aromatic compounds by experimental and theoretical analysis. The theoretical analysis were done with Time-Dependent Density Functional Theory (TD-DFT) and B3LYP/6-31G (d,p) basis set, whereas, Polarizable Continuum Model (PCM) was used to consider water as solvent. The selected compounds displayed their own specific excitation-emission (Ex/Em) wavelengths region, at Ex<280 nm and Em<340 nm, respectively. Whereas the theoretical Ex/Em was observed as, Ex at 240 nm–260 nm and Em at 255 nm–300 nm. Aniline as a strong aromatic base has longer Em (340 nm) than alkyl, carbonyl, and halogens substituted benzenes. The lone pair of electrons at amide substituent serves as a p-electron contributor into the aromatic ring, hence increasing the stability and transition energy, which results in longer emission and low quantum yield for the aniline. The fluorescence of halogenated benzenes illustrates an increase in the HOMO-LUMO energy gap and a decrease in quantum yield associated with atomic size (F>Cl>Br>I). In this study the theoretical results are in line with experimental ones. The understanding of fluorescence and photophysical properties are of great importance in the identification of these compounds in the water.

关键词： Fluorescence     Photophysical properties     Effect of the substituent     Toxic aromatic compounds    

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Cd-tolerant electrochemically active bacteria in MECs toward exotic Cr(VI) based on the sensing of fluorescence

Xia Hou, Liping Huang, Peng Zhou, Hua Xue, Ning Li

《环境科学与工程前沿（英文）》 2018年 第12卷 第4期 doi: 10.1007/s11783-018-1057-4

摘要：

Cell membrane of indigenous Cd-tolerant EAB harbored more cadmium than chromium.

Indigenous Cd-tolerant EAB cytoplasm located more chromium than cadmium.

Simultaneously quantitatively imaging Cd(II) and Cr(III) ions in EAB was achieved.

Current accelerated the harboring of cadmium in EAB at an initial 2 h.

Current directed the accumulation of more chromium in EAB over time.

关键词： Microbial electrolysis cell     Electrochemically active bacteria     Cd-tolerant bacteria     Cd(II) and Cr(VI)     Fluorescence probe    

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标题 作者 时间 类型 操作

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

期刊论文

基于荧光原位杂交技术的UASB颗粒污泥中苯酚降解微生物生态位分化研究

Kengo Kubota, Kei Igarashi, Masayoshi Yamada, Yasuyuki Takemura, Yu-You Li, Hideki Harada

期刊论文

Short-term effects of excessive anaerobic reaction time on anaerobic metabolism of denitrifying polyphosphate- accumulating organisms linked to phosphorus removal and N

Gang GUO, Yayi WANG, Chong WANG, Hong WANG, Mianli PAN, Shaowei CHEN

期刊论文

hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

期刊论文

Short-term effect of temperature variation on the competition between PAOs and GAOs during acclimation period of an EBPR system

Nanqi REN, Han KANG, Xiuheng WANG, Nan LI

期刊论文

Comments on “Determination of heterozygosity for avirulence/virulence loci through sexual hybridization

Ralf T. Voegele

期刊论文

Determination of heterozygosity for avirulence/virulence loci through sexual hybridization of

Yuan TIAN,Gangming ZHAN,Xia LU,Jie ZHAO,Lili HUANG,Zhensheng KANG

期刊论文

Effect of fiber hybridization on energy absorption and synergy in concrete

Ahmadreza RAMEZANI, Mohammad Reza ESFAHANI

期刊论文

Development and application of ex-situ presulfurization technology for hydrotreating catalysts in China

Yulan GAO, Xiangchen FANG, Zhenmin CHENG

期刊论文

Synthesis and fluorescence behavior of 2,5-diphenyl-1,3,4-oxadiazole-containing bismaleimides and bissuccinimides

Xin ZHANG, Zichen LI

期刊论文

Polyolefin-nanocomposites with special properties by in-situ polymerization

Walter Kaminsky

期刊论文

Synthesis and characterization of 2,5-bis[4-(2-arylvinyl)phenyl]-1,3,4-oxadiazoles with two-photon fluorescence

ZHU Xiaoqin, QIAN Ying, LU Zhifeng

期刊论文

Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

期刊论文

Insight into fluorescence properties of 14 selected toxic single-ring aromatic compounds in water: Experimental

Muhammad Farooq Saleem Khan, Jing Wu, Cheng Cheng, Mona Akbar, Chuanyang Liu, Bo Liu, Jian Shen, Yu Xin

期刊论文

Cd-tolerant electrochemically active bacteria in MECs toward exotic Cr(VI) based on the sensing of fluorescence

Xia Hou, Liping Huang, Peng Zhou, Hua Xue, Ning Li

期刊论文