查找使用阿拉丁产品的科研文献

Synergistic D-Amino Acids Based Antimicrobial Cocktails Formulated via High-Throughput Screening and Machine Learning

Jingzhi Yang,Yami Ran,Shaopeng Liu,Chenhao Ren,Yuntian Lou,Pengfei Ju,Guoliang Li,Xiaogang Li,Dawei Zhang

Antimicrobial resistance (AMR) from pathogenic bacterial biofilms has become a global health issue while developing novel antimicrobials is inefficient and costly. Combining existing multiple drugs with enhanced efficacy and/or reduced toxicity may be a promising approach to treat AMR. D-amino acids mixtures coupled with antibiotics can provide new therapies for drug-resistance infection with reduced toxicity by lower drug dosage requirements. However, iterative trial-and-error experiments are not tenable to prioritize credible drug formulations, owing to the extremely large number of possible combinations. Herein, a new avenue is provide to accelerate the exploration of desirable antimicrobial formulations via high-throughput screening and machine learning optimization. Such an intelligent method can navigate the large search space and rapidly identify the D-amino acid mixtures with the highest anti-biofilm efficiency and also the synergisms between D-amino acid mixtures and antibiotics. The optimized drug cocktails exhibit high antimicrobial efficacy while remaining non-toxic, which is demonstrated not only from in vitro assessments but also the first in vivo study using a lung infection mouse model.

Enhancement of the substrate specificity of D-amino acid oxidase based on tunnel-pocket engineering

Liuyu Wang,Heng Tang,Hongli Zhu,Yaping Xue,Yuguo Zheng

D -Amino acid oxidase (DAAO) selectively catalyzes the oxidative deamination of D -amino acids, making it one of the most promising routes for synthesizing optically pure L -amino acids, including L -phosphinothricin ( L -PPT), a chiral herbicide with significant market potential. However, the native DAAOs that have been reported have low activity against unnatural acid substrate D -PPT. Herein, we designed and screened a DAAO from Rhodotorula taiwanensis ( Rtw DAAO), and improved its catalytic potential toward D -PPT through protein engineering. A semirational design approach was employed to create a mutation library based on the tunnel-pocket engineering. After three rounds of iterative saturation mutagenesis, the optimal variant M 3rd -SHVG was obtained, exhibiting a >2000-fold increase in relative activity. The kinetic parameters showed that M 3rd -SHVG improved the substrate binding affinity and turnover number. This is the optimal parameter reported so far. Further, molecular dynamics simulation revealed that the M 3rd -SHVG reshapes the tunnel-pocket and corrects the direction of enzyme–substrate binding, allowing efficiently catalyze unnatural substrates. Our strategy demonstrates that the redesign of tunnel-pockets is effective in improving the activity and kinetic efficiency of DAAO, which provides a valuable reference for enzymatic catalysis. With the M 3rd -SHVG as biocatalyst, 500 mM D, L -PPT was completely converted and the yield reached 98%. The results laid the foundation for further industrial production.

Open-Set Recognition for Unknown Organic Pollutants in Drinking Water With 3-D Fluorescence Spectroscopy

Hang Yin,Jie Yu,Fei Shi,Fangjia Xue,Jiegen Shi,Pingjie Huang,Dibo Hou

Sensitive detection and imaging of endogenous peroxynitrite using a benzo[d]thiazole derived cyanine probe

Tianxin Hou,Kui Zhang,Xiaoxuan Kang,Xueling Guo,Libo Du,Xinfeng Chen,Long Yu,Ji Yue,Hongwei Ge,Yang Liu,Abdullah M. Asiri,Khalid A. Alamry,Huan Yu,Suhua Wang

Peroxynitrite is a short-lived endogenous reactive species and plays important roles in many physiological and pathological processes. In this work, we synthesized a near-infrared probe based on the structure of benzothiazole derived cyanine for determination of peroxynitrite (ONOO - ). The designed probe specifically reacted with ONOO - through oxidative cleavage of conjugated C˭C double bonds and generating the non-fluorescent product. Meanwhile, the characteristic absorption of the probe at 630 nm greatly decreased after reaction with ONOO - , accompanied by drastic color change from bright blue to green yellow, which exhibited a distinct visual feature. It was demonstrated that the probe could be used to measure ONOO - in a dose-response manner and had a detection limit lower as 26 nM. Furthermore, the probe Cy-SN was applied for the imaging of endogenous ONOO - in living cells by confocal microscopy , which showed good cell permeability and low cytotoxicity. Successful application of probe for exogenous colorimetric detection and endogenous fluorescence imaging of ONOO - is suggesting its great potential applications in biological analysis.

Solubility of d-Tryptophan and l-Tyrosine in Several Organic Solvents: Determination and Solvent Effect

Xinbao Li,Kaihui Li,Ali Farajtabar,Yating He,Gaoquan Chen,Hongkun Zhao

The solubilities of d-tryptophan in neat n-propanol, ethyl acetate, ethylene glycol (EG), n-butanol, acetonitrile, 1-octanol, and dimethyl sulfoxide and of l-tyrosine in ethyl acetate, EG, isopropanol, acetonitrile, n-butanol, and N,N-dimethylformamide (DMF) were determined via a shake-flask method at temperatures from 283.15 to 328.15 K under about 101.2 kPa. At the fixed temperature, the mole fraction solubility of d-tryptophan was the largest in EG and the lowest in 1-octanol. However, for l-tyrosine, the maximum solubility was observed in the ethyl acetate and minimum in n-butanol. X-ray powder diffraction analysis was carried out to analyze the solids equilibrated with the corresponding liquor, indicating that no polymorphic transformation or solvate formation took place in the studied systems. The solubility correlation was performed via the Apelblat equation. The obtained maximum root-mean-square deviation and relative average deviation values were 13.65 × 10–5 and 4.32%, respectively. In addition, the solvent–solvent and solute–solvent interactions were investigated on the basis of the approach of linear solvation energy relationship.

Fluorination effects of A-D-A small molecule donors based benzotriazole for organic solar cells

Huihui Gu,Yuancheng Qin,Weili Dai,Dan Zhou,Yu Xie

To explore the effect of fluorine atom on photophysical properties, in this work, we synthesized three new small molecules (SMs) with acceptor-donor-acceptor (A-D-A) configuration, SM-0F , SM-2F and SM-4F , where 4,8-bis(octyloxy)benzo[1,2-b:4,5-b']dithiophene ( BDT ) as the electron-donating and benzo[d][1,2,3]triazole ( BTA ) or fluorinated BTA as electron-withdrawing. The three small molecules exhibit good solubility and thermal stability as well as strong absorption. The fluorination of BTA unit made SM-2F and SM-4F possess a relatively lower the highest occupied molecular orbital (HOMO) and higher electron mobility in comparison with SM-0 F. We treated the three small molecules as donor and PC 71 BM as the acceptor to manufacture small molecule organic solar cells. After introduction of F, the power conversion efficiency (PCE) is improved. Among them, device based on SM-2F gave the best device performance with a PCE of 3.94% with J sc of 11. 37 mA/cm 2 , V oc of 0.76 V, fill factor ( FF ) of 0.45. These studies show that the incorporation of fluorine atom is an effective method to increase the efficiency of organic solar cells.

Phospholipase D encapsulated into metal-surfactant nanocapsules for enhancing biocatalysis in a two-phase system

Hui Li,Yang Pang,Xin Wang,Xun Cao,Xun He,Kequan Chen,Ganlu Li,Pingkai Ouyang,Weiming Tan

Methods for enhancing enzyme activities in two-phase systems are getting more attention. Phospholipase D (PLD) was successfully encapsulated into metal-surfactant nanocapsules (MSNCs) using a one-pot self-assembly technique in an aqueous solution. The highest yield for the production of high-value phosphatidylserine (PS) from low-value phosphatidylcholine (PC) in the two-phase system was achieved by encapsulating PLD into MSNCs formed from Ca2+ which gave an enzyme activity that was 133.6% of that of free PLD. The PLD@MSNC transformed the two-phase system into an emulsion phase system and improved the organic solvent tolerance, pH and thermal stabilities as well as the storage stability and reusability of the enzyme. Under optimal conditions, PLD@MSNC generated 91.9% PS over 8 h in the two-phase system, while free PLD generated only 77.5%.

Biosynthesis of Phenylglyoxylic Acid by LhDMDH, a Novel d-Mandelate Dehydrogenase with High Catalytic Activity

Cun-Duo Tang,Hong-Ling Shi,Jian-He Xu,Zhu-Jin Jiao,Fei Liu,Peng-Ju Ding,Hong-Fei Shi,Lun-Guang Yao,Yun-Chao Kan

d-Mandelate dehydrogenase (DMDH) has the potential to convert d-mandelic acid to phenylglyoxylic acid (PGA), which is a key building block in the field of chemical synthesis and is widely used to synthesize pharmaceutical intermediates or food additives. A novel NAD+-dependent d-mandelate dehydrogenase was cloned from Lactobacillus harbinensi (LhDMDH) by genome mining and expressed in Escherichia coli BL21. After being purified to homogeneity, the oxidation activity of LhDMDH toward d-mandelic acid was approximately 1200 U·mg–1, which was close to four times the activity of the probe. Meanwhile, the kcat/Km value of LhDMDH was 28.80 S–1·mM–1, which was distinctly higher than the probe. By coculturing two E. coli strains expressing LhDMDH and LcLDH, we developed a system for the efficient synthesis of PGA, achieving a 60% theoretical yield and 99% purity without adding coenzyme or cosubstrate. Our data supports the implementation of a promising strategy for the chiral resolution of racemic mandelic acid and the biosynthesis of PGA.

Toxicity testing of four silver nanoparticle-coated dental castings in 3-D LO2 cell cultures

Yi-ying Zhao,Qiang Chu,Xu-er Shi,Xiao-dong Zheng,Xiao-ting Shen,Yan-zhen Zhang

To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical applications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.

One-dimensional controllable crosslinked polymers grafted with N-methyl-D-glucamine for effective boron adsorption

Jingjing Kang,Yakun Tang,Shasha Gao,Lang Liu

In this research, a series of one-dimensional controllable crosslinked polymers with the different mass ratios of 4-vinylbenzychloride (VBC) and divinyl benzene (DVB) was prepared via cationic polymerization, and the polymers were grafted with the functional group N-methyl-D-glucamine (NMDG) for boron removal. The optimum polymeric mass ratio and a series of boron adsorption performances were studied. The maximum adsorption capacity was 18.15 mg g−1, of which 94% was retained after 4 cycles. Meanwhile, different pH values had negligible effect on the boron adsorption capacity, which was favorable for the removal of boron from its aqueous solution in a wide pH window. In addition, a magnetic adsorbent was prepared by the combination of Fe3O4 nanoparticles and the polymer, which provided an effective way to collect and recover adsorbents from their aqueous solutions.

Dehydration of D-xylose into furfural over bimetallic salts of heteropolyacid in DMSO/H2O mixture

Xiaoqian Guo,Feng Guo,Yishan Li,Zhangqin Zheng,Zhexu Xing,Zihan Zhu,Ting Liu,Xin Zhang,Ying Jin

Dehydration of D-xylose to yield furfural was carried out using bimetallic salts of a heteropolyacid as the catalyst at 160–220 °C in the DMSO/H 2 O mixtures. The effect of Sn/Cs molar ratio of the bimetallic salts of 12-tungstophosphoric acid (PW) obtained by ultrasound-assisted coprecipitation on dehydration of D-xylose was investigated. The resultant catalysts were characterized by X-ray diffraction, N 2 adsorption, field emission scanning electron microscopy and energy dispersive X-ray (EDX). It was found that the Sn-Cs codoped PW catalysts retained the Keggin crystal structure of PW. Sn 0.625 Cs 0.5 PW was the most active catalyst in the dehydration of D-xylose into furfural. The maximum D-xylose conversion (close to 100 wt %) and furfural yield (63 wt %) were achieved at 200 °C for 3 h in DMSO/H 2 O mixtures. It was found that 16.7 wt % Sn 0.625 Cs 0.5 PW on a chitosan-derived support displayed similar catalytic activity to that of Sn 0.625 Cs 0.5 PW and good stability after recycling six times.

Chiral ligand exchange capillary electrochromatography with dual ligands for enantioseparation of D,L-amino acids

Wenya Feng,Juan Qiao,Dan Li,Li Qi

Utilizing block copolymers as coatings, a protocol of chiral ligand exchange capillary electrochromatography (CLE-CEC) protocol was designed and developed with dual ligands for D,L-amino acids enantioseparation. Four block copolymers including poly maleic anhydride- co -styrene- co -N-methacryloyl- L -histidine methyl ester [P(MAn-St-MAH)], poly maleic anhydride- co -styrene- co -N-methacryloyl- L -lysine methyl ester [P(MAn-St-MAL)], poly maleic anhydride- co -styrene- co -N-methacryloyl- L -phenylalanine methyl ester [P(MAn-St-MAP)] and poly maleic anhydride- co -styrene- co -N-methacryloyl- L -threonine methyl ester [P(MAn-St-MAT)] were synthesized by reversible addition fragmentation chain transfer polymerization reaction. Key factors affecting the enantioresolution were optimized, including the concentration of Zn (II) central ion, pH value of buffer solution and monomers of the block copolymers. The enantioresolution of the proposed CLE-CEC system could be enhanced dramatically by employing P(MAn-St-MAH) as the immobilized chiral ligand and by coordinating the synergistic effect of free ligand in buffer solution. The principle of improved enantioresolution of the CLE-CEC system with dual ligands was discussed. Well enantioseparation was successfully realized with 7 pairs of D,L-amino acids enantiomers baseline separation and 5 pairs part separation. For quantitative analysis of D, L -alanine, a good linearity was established in the range of 9.4 μM to 1.5 mM (r 2 = 0.997) with the limits of detection (LODs) 3.7 μM of D -alanine, 2.0 μM for L -alanine, and limits of quantification (LOQs) 9.0 μM for D -alanine and 6.0 μM for L -alanine. The peak area and migration time reproducibility (n = 6) were 4.1% and 3.5% for D -alanine, 3.7% and 3.1% for L -alanine. Further, the enzyme kinetics study of alanine aminotransferase was investigated with the constructed CLE-CEC system.