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LAB ON A CHIP · 2023 ·Vol. 23 ·期 18 ·3961-3977 · IF 6.1

Artificial intelligence-accelerated high-throughput screening of antibiotic combinations on a microfluidic combinatorial droplet system

Deyu Yang,Ziming Yu,Mengxin Zheng,Wei Yang,Zhangcai Liu,Jianhua Zhou,Lu Huang

Microfluidic platforms have been employed as an effective tool for drug screening and exhibit the advantages of lower reagent consumption, higher throughput and a higher degree of automation. Despite the great advancement, it remains challenging to screen complex antibiotic combinations in a simple, high-throughput and systematic manner. Meanwhile, the large amounts of datasets generated during the screening process generally outpace the abilities of the conventional manual or semi-automatic data analysis. To address these issues, we propose an artificial intelligence-accelerated high-throughput combinatorial drug evaluation system (AI-HTCDES), which not only allows high-throughput production of antibiotic combinations with varying concentrations, but can also automatically analyze the dynamic growth of bacteria under the action of different antibiotic combinations. Based on this system, several antibiotic combinations displaying an additive effect are discovered, and the dosage regimens of each component in the combinations are determined. This strategy not only provides useful guidance in the clinical use of antibiotic combination therapy and personalized medicine, but also offers a promising tool for the combinatorial screenings of other medicines.

研究领域: 药学 · 微流控技术 · 人工智能 · 生物医学工程
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CERAMICS INTERNATIONAL · 2022 · IF 5.532

A strategy of combination reaction to improve electrochemical performance in two-dimensional Mo1-xWxSe2 battery-type electrode materials

Yang Gao,Kai Liu,Yingjun Wu,Caijuan Li,Qiang Lü,Guomei Zu

We report here a case of combination reaction between MoSe 2 and WSe 2 in certain proportions to improve electrochemical performance of Mo 1- x W x Se 2 compound materials. Two-dimensional (2D) Mo 1- x W x Se 2 flower-like crystals (x = 0, 0.25, 0.5, 0.75, 1) were synthesized using a solution synthesis method, and then Mo 1- x W x Se 2 -based electrodes were prepared using a powder pellet method. Their structure and electrochemical performance were respectively measured by X-ray diffraction (XRD), transmission electron microscope (TEM), X-ray photoelectron spectrometer (XPS), scanning electron microscope (SEM), and electrochemical workstation. The results indicate that only Mo 0.25 W 0.75 Se 2 -based electrode (x = 0.75), compared with other electrodes, delivers excellent specific capacity and stability with the capacity retention of 74.4% after 5000 charging-discharging deep cycles at the current density of 2 A g −1 in 1.0 mol/L KOH aqueous electrolyte, and exhibits a Coulombic efficiency almost 100% after 5000 cycles. This phenomenon is attributed to a situation that Mo 0.25 W 0.75 Se 2 active material has a quite different electronic band structure from the other remaining materials. It is therefore concluded that the combination reaction enables Mo 1- x W x Se 2 composite materials to realize their potential in electrochemical energy storage.

研究领域: 材料科学 · 电化学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2018 · IF 3.997

The influence of combination mode on the structure and properties of graphene quantum dot-porphyrin composites

Xue Gao,Bing Zhang,Qiang Zhang,Yiwei Tang,Xiuying Liu,Jianrong Li

As a rising star in the family of fluorescent material, graphene quantum dots (GQDs) have attracted great attention because of their excellent properties such as high photostability against photobleaching and blinking, biocompatibility, and low toxicity. Herein, strongly fluorescent GQDs have been prepared by one-step solvothermal method. Then three kinds of GQDs-porphyrin composites were assembled by means of noncovalent interaction. It was found that the functional groups on the peripheries of the porphyrin were important on the combination mode of porphyrin and GQDs. The fluorescence of GQDs was quenched in the presence of the porphyrin . The suggested quenching mechanism is through Förster resonance energy transfer (FRET). Tetrasodium-meso-tetra(4-sulfonatophenyl) porphine dodecahydrate (NaTSPP) was easy to react with GQDs and flat on the GQDs due to the strong hydrogen bond and π-π interaction. The photoelectronic activity of the GQDs-NaTSPP composite was higher than those of the other two GQDs-porphyrin composites. These results provided some hints for how to adjust the properties of the GQDs-porphyrin composites by modifying the combination mode between porphyrins and GQDs. These novel GQDs-porphyrin composites hold promise for various optical and luminescence-based applications.

研究领域: 材料科学 · 光学
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Chemical Science · 2015 ·Vol. 7 ·期 3 ·1853-1861 · IF 9.211

A RET-supported logic gate combinatorial library to enable modeling and implementation of intelligent logic functions

Ru-Ru Gao,Shuo Shi,Ying Zhu,Hai-Liang Huang,Tian-Ming Yao

Boolean logic gates integrate multiple digital inputs into a digital output. Among these, logic gates based on nucleic acids have attracted a great deal of attention due to the prospect of controlling living systems in the way we control electronic computers. Herein, by employing Thioflavin T (ThT) as a signal transducer, we integrated multiple components based on RET (a type of proto-oncogene) into a logic gate combinatorial library, including basic logic gates (NOR, INHIBIT, IMPLICATION), a single three-input NOR gate, and combinatorial gates (INHIBIT–OR, NOT–AND–NOR). In this library, gates were connected in series where the output of the previous gate was the input for the next gate. Subsequently, by taking advantage of the library, some intelligent logic functions were realized. Expectedly, a biocomputing keypad-lock security system was designed by sequential logic operations. Moreover, a parity checker which can identify even numbers and odd numbers from natural numbers was established successfully. This work helps elucidate the design rules by which simple logic can be harnessed to produce diverse and complex calculations by rewiring communication between different gates. Together, our system may serve as a promising proof of principle that demonstrates increased computational complexity by linking multiple logic gates together.

研究领域: 合成生物学 · 分子生物学
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BIORESOURCE TECHNOLOGY · 2024 · IF 9.7

Investigating enhancement of protease and lysozyme combination pretreatment on hydrolysis of sludge organics under humic acid inhibition

Xiang Zou,Junguo He,Xinlei Pan,Qiupeng Cai,Shengye Duan,Yijie Zhong,Xinxin Cui,Jie Zhang

This study investigated the impact of humic acid (HA) on enzymatic pretreatment efficiency, focusing on sludge properties and HA molecular structure. The results showed that enzymatic pretreatment alleviates HA inhibition, improving hydrolysis efficiency. In the presence of HA, soluble proteins and polysaccharides in the enzyme-cocktail group reached 27.7 mg/L and 23.9 mg/L, 1.4 and 1.3 times higher than the blank group, respectively. The enzyme-cocktail group also had the highest soluble DNA concentration (19.4 mg/L) and the lowest viable cell proportion (69.3 %), indicating effective cell lysis. Enzyme-cocktail pretreatment reduced electrostatic repulsion, enhancing the mobility of extracellular organics. Enzyme interactions with HA released internal hydrolases and decreased amide groups on the HA surface, increasing the availability of biodegradable substrates. Overall, enzymatic pretreatment proves effective in mitigating HA-induced inhibition, thereby improving sludge biodegradation and enhancing carbon recovery in anaerobic fermentation.

CAS / MDL: 1415-93-6 9001-92-7
研究领域: 环境生物学 · 生物化学
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE · 2024 · IF 3.3

Highly efficient expression of Rasamsonia emersonii lipase in Pichia pastoris: characterization and gastrointestinal simulated digestion in vitro

Buqing Wang,Yasen Wang,Xiaoman Zhou,Xiao-Dong Gao,Morihisa Fujita,Zijie Li

BACKGROUND Acidic lipases with high catalytic activities under acidic conditions have important application values in the food, feed and pharmaceutical industries. However, the availability of acidic lipases is still the main obstacle to their industrial applications. Although a novel acidic lipase Rasamsonia emersonii (LIPR) was heterologously expressed in Escherichia coli , the expression level was unsatisfactory. RESULTS To achieve the high-efficiency expression and secretion of LIPR in Pichia pastoris GS115, the combinatorial optimization strategy was adopted including gene codon preference, signal peptide, molecular chaperone co-expression and disruption of vacuolar sorting receptor VPS10 . The activity of the combinatorial optimization engineered strain in a shake flask reached 1480 U mL −1 , which was 8.13 times greater than the P. pastoris GS115 parental strain. After high-density fermentation in a 5-L bioreactor, the highest enzyme activity reached as high as 11 820 U mL −1 . LIPR showed the highest activity at 40 °C and pH 4.0 in the presence of Ca 2+ ion. LIPR exhibited strong tolerance to methanol, indicating its potential application in biodiesel biosynthesis. Moreover, the gastrointestinal digestion simulation results demonstrated that LIPR was tolerant to pepsin and trypsin, but its activity was inhibited by sodium taurodeoxycholate. CONCLUSION This study provided an effective approach for the high expression of acidic lipase LIPR. LIPR was more appropriate for lipid digestion in the stomach than in intestine according to the gastrointestinal digestion simulation results. © 2024 Society of Chemical Industry.

研究领域: 生物技术 · 酶工程 · 食品科学
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CRYSTENGCOMM · 2014 ·Vol. 16 ·期 30 ·6996-7003 · IF 3.858

Structural and physicochemical aspects of hydrochlorothiazide co-crystals

Jian-Rong Wang,Chanjuan Ye,Xuefeng Mei

Crystal engineering principles were employed in designing new co-crystals of hydrochlorothiazide (HCT). A variety of potential co-crystal formers were initially identified in a search of the Cambridge Structural Database with complementary hydrogen-bonding functionalities. Subsequent co-crystallization screening monitored by powder X-ray diffraction led to the discovery of new crystalline phases of HCT with pyrazinamide (1), 4,4′-bipyridine (2), 1,2-bis(4-pyridyl)ethane (3), and trans-1,2-bis(4-pyridyl)ethylene (4). All of the resulting co-crystals were thoroughly characterized by X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analysis. Noticeably, the co-crystal 1 involves the formation of drug–drug co-crystals of HCT and pyrazinamide, which makes it a potential candidate for development of HCT formulations for combinational therapy.

CAS / MDL: 553-26-4
研究领域: 药学 · 材料科学
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Micromachines · 2022 ·Vol. 14 ·期 1 ·45 · IF 3.523

Micromixing Intensification within a Combination of T-Type Micromixer and Micropacked Bed

Zhou Lan,Yangcheng Lu

The combination of microstructural units is an effective strategy to improve the micromixing of liquid phase systems, especially viscous systems. However, how the microstructural combination influences micromixing is still not systematically investigated. In this work, the Villermaux/Dushman reaction is used to study the micromixing performance of the viscous system of the glycerol–water in the combination of a T-type micromixer and a micropacked bed. Micromixing performances under various structural parameters and fluid characteristics are determined and summarized, and the micromixing laws are revealed by dimensionless analysis considering the specific spatial characteristics and temporal sequence in the combined microstructures. It achieves good agreement with experimental results and enables guidance for the design and scaling-up of the combined T-type micromixer and micropacked bed towards micromixing intensification in viscous reaction systems.Keywords:micromixing;micropacked bed;microstructual combination;viscous system

研究领域: 化学工程 · 流体力学
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Desalination and Water Treatment · 2024 · IF 1

Boron removal by iron-aluminum combined anodes from fracturing flowback fluid: Advantages and mechanisms

Ying Zhang,Xule Chen,Miao Dong,Meiyan Li,Chengwen Wang,Yanzong Zhang

During the process of oilfield wastewater reuse, residual Boron in fracturing flowback fluid will lead to premature crosslinking with gelling agents, resulting in excessive viscosity at the front end of the fracturing fluid configuration. This phenomenon has heavily influenced the reuse of wastewater. Electrocoagulation (EC), as an effective approach to decreasing Boron concentration, has been widely studied, while further research of Boron removal from complicated wastewater is required to optimize. EC parameters were investigated to explore the optimal Boron removal effect of Fe, Al and Fe-Al three combined anodes. Under 46.3–57.2 mA/cm 2 , 90 min and pH of 9, Fe-Al anodes exhibit the best effect of Boron removal (84% ± 1.5%). Furthermore, high adaptive capacity of low current density and suitable pH confirm the best choice of Fe-Al combined anodes. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrate the complexation between Boron and metallic oxide. Finally, the common removal of various pollutants including Ca, Cl, K and Na further conduces to the reuse of oil wastewater.

CAS / MDL: 206752-32-1
研究领域: 环境科学 · 废水处理
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PEST MANAGEMENT SCIENCE · 2019 ·Vol. 76 ·期 2 ·589-596 · IF 3.255

Efficacy of binary combinations between methyl salicylate and carvacrol against thrips Anaphothrips obscurus: laboratory and field trials

Xiao-Peng Lu,Jia-Huan Liu,Hua Weng,Zhi-Qing Ma,Xing Zhang

BACKGROUND Thrips Anaphothrips obscurus are one of the cosmopolitan major pests feeding on cereals and other grasses. In order to develop alternatives of chemical insecticides for thrips control, based on fumigant activity screening and evaluation of 22 essential oil (EO) compounds against the thrips, the binary interactions of methyl salicylate and carvacrol (MS-C) with high fumigant toxicity were studied systematically by bioassay and field trials. RESULTS The bioassay results showed that six in 22 EO compounds had high fumigant toxicity against both the second-instar nymphs and adults of A. obscurus , including methyl salicylate, carvacrol, thymol, trans -cinnamaldehyde, diallyl trisulfide, and L-perillaldehyde. Furthermore, the combination of methyl salicylate mixed with carvacrol at a volume ratio of 5:5 exhibited the most significant synergism against A. obscurus , with a poison ratio value of 1.32 and a co-toxicity coefficient of 151.15. The optimal formulation of microemulsion (ME) was composed of 5% methyl salicylate, 5% carvacrol, 46% adjuvant and 44% deionized water. The result of dynamic light scattering and stability showed that MS-C 10% ME was a transparent, single-phase and homogeneous liquid system. Field trials indicated that the ME displayed a significant control efficacy of about 89.17% on thrips in peppers, and 82.59% in broad bean on the seventh day post application with a dosage of 600.0 g A.I hm –2 , respectively. CONCLUSION The binary combination of MS-C possesses strikingly synergistic action against thrips A. obscurus , and the MS-C 10% ME has the potential to be developed as a botanical pesticide product for thrips control. © 2019 Society of Chemical Industry

研究领域: 植物保护 · 昆虫学
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BIOCHEMICAL ENGINEERING JOURNAL · 2021 · IF 3.978

Assessment of enzyme addition strategies on the enhancement of lipid yield from microalgae

Yi Zhang,Xihui Kang,Feng Zhen,Zhongming Wang,Xiaoying Kong,Yongming Sun

Enzymatic hydrolysis is emerging as a promising unconventional pretreatment method for disrupting microalgae cells. However, the sustainability of biological enzyme needs to be improved due to low efficiency of enzymatic hydrolysis with single enzyme. Cellulase , xylanase , pectinase , snailase, lysozyme and trypsin were selected to pretreat microalgae Scenedesmus sp. for lipid extraction. The results shown that the pretreatment of a multi-enzyme combination of cellulase, xylanase and pectinase perform a better enzymatic hydrolysis effect than each single enzyme. Results shown that different sequences of enzymatic hydrolysis had a significant effect on the lipid extraction performance from microalgae, the lipid recovery yield of 100% (total lipids content) could be achieved with the sequence of stepwise enzymatic hydrolysis: pectinase (10 mg g -1 dry weight microalgae), cellulase (20 mg g -1 ) and xylanase (14 mg g -1 ). The SEM image, FTIR measurement, HPLC and XPS analysis indicated that the outer layer of trilaminar sheaths in the microaglal cell walls was first degraded by pectinase, and then cellulose and hemicellulose in the inner layer were destroyed by cellulase and xylanase. This study provides an efficient and environmental-friendly route for lipid extraction as a new strategy of enzymatic hydrolysis to valorize high-value added products in microalgae downstream processing .

研究领域: 生物技术 · 可再生能源
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Molecular Catalysis · 2023 · IF 4.6

Alleviating the trade-off by site-guided function switch of nitrilase to nitrile hydratase

Yangyang Sun,Zhuzhu Tang,Tingze Pan,Ke Zhang,Liuzhu Wang,Xingye Zhai,Yiran Jia,Tianqi Yuan,Yujia Qian,Hualei Wang,Dongzhi Wei,Shengli Yang

Catalytic promiscuity makes nitrilase-mediated unnatural reactivity a promising pathway in the production of primary amides . However, during the functional switch of nitrilase, a trade-off between the newly developed hydration activity and relative activity hinders the application of nitrilase in the production of amides. Our previous study showed that the mutant F193N (Mut0) of nitrilase NIT6803 from Synechocystis sp. PCC6803 improved the hydration activity as the amide ratio increased to 73.4%, whereas the relative activity was only 50.1% of that of the wild-type (WT). In this study, we succeeded in alleviating the trade-off of Mut0 through an evolutionary combination of the key identified sites 101, 192, and 201. Inside the active pocket, the co-evolution of residue Q192 was identified by hotspot prediction to correlate with N193, and Q192H exhibited an improved amide ratio of 76.9% with a relative activity of up to 72%. Outside the active pocket, the flexible loop surface residue G101 and homodimer “A” interface residue I201 were identified using sequence alignment-based mutations. Further evolutionary combination of the three key sites yielded the best triple mutant G101K/Q192H/I201M, which had the highest amide ratio of 98.5% and considerably recovered relative activity of 82.6% while retaining only 1.5% of the carboxylic acid ratio. The transition-state analogue sheds light on the basis of the almost identical switch of the reaction pathways, and our results expand the toolbox of nitrilase-catalysed promiscuity for amide formation.

研究领域: 生物化学 · 酶工程
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