ACS Synthetic Biology
·
2025
·
IF 3.9
Bicheng Yu,Wei Song,Shenjie Wang,Wanqing Wei,Guipeng Hu,Xiaomin Li,Cong Gao,Jia Liu,Jian Wen,Jing Wu
2-Pyrrolidone is an important chemical intermediate with broad applications in the materials and pharmaceutical industries. Traditional petrochemical synthesis methods pose significant environmental challenges. In the case of biosynthesis, the limited thermostability of coenzyme A ligase (CaiC) represents a major barrier to industrial-scale production. This study focused on enhancing the thermostability and catalytic efficiency of EcCaiC through protein engineering. Conserved sequences were identified, and flexible regions were targeted for virtual mutagenesis using FoldX and Rosetta. The resulting mutant, M3, exhibited a 7.86-fold increase in half-life(t1/2) at 55 °C and a Tm of 59.3 °C. Additionally, the catalytic efficiency (kcat/Km) of M3 improved by 52.8%, reaching 5.73 mM–1 s–1 compared to the wild type. Subsequently, EcCaiCM3 was introduced into Corynebacterium glutamicum S9114, with targeted knockout of byproduct synthesis genes. Finally, fed-batch fermentation in a 5 L bioreactor achieved a 2-pyrrolidone yield of 58.28 g/L, a glucose conversion rate of 0.32 g/g, and a productivity of 0.97 g/L/h. This work establishes an efficient biosynthetic platform for 2-pyrrolidone, providing a robust foundation for its industrial production.
研究领域:
生物化学
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工业微生物学
·
蛋白质工程
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DOI
PubMed
高影响因子
ChemMedChem
·
2025
·
IF 3.4
Xinlin Zhu,Qin Li,Junhui Wu,Zhiran Ju
Graphical In recent years, the development of COX-2 inhibitors has shifted from a focus on highly selective inhibition to emphasizes more moderate selectivity. This study presents a potent balanced COX-2 inhibitor, compound 21d, which effectively alleviates histological damage and provides protection against DSS-induced colitis. The severe adverse effects associated with imbalanced cyclooxygenase-2 (COX-2) inhibition continue to pose significant challenges in the development of contemporary anti-inflammatory drugs. In recent years, the approach to COX-2 inhibitor drug development has shifted from a focus on highly selective inhibition of COX-2 to a strategy that emphasizes more moderate selectivity. The amino acid sequence and structural similarities between inducible COX-2 and constitutive cyclooxygenase-1 (COX-1) isoforms present both substantial opportunities and challenges for the design of next generation of balanced COX-2 inhibitors. As part of our ongoing research into the discovering novel and safer COX-2 inhibitors, we reported herein a highly potent and balanced COX-2 inhibitor 21 d (IC 50 value=1.35 μM, selectivity profile (IC 50 (COX-1)/IC 50 (COX-2)=22.34)). In vivo assays demonstrated that 21 d significantly alleviated histological damage and provided robust protection against dextran sulfate sodium (DSS)-induced acute colitis.
研究领域:
药理学
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分子生物学
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药物开发
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Liu Shi,Lin Wang,Xuemei Ma,Xiaona Fang,Liangliang Xiang,Yongxiang Yi,Jinlong Li,Zhaofeng Luo,Genxi Li
With the outbreak of COVID-19, which is fast transmitting and highly contagious, the development of rapid, highly specific, and sensitive detection kits has become a research hotspot. The existing assay methods for SARS-CoV-2 are mainly based on enzymatic reactions, which require expensive reagents, hindering popular use, especially in resource-constrained areas. Herein, we propose an aptamer-based method for the assay of SARS-CoV-2 via binding of the spike protein using functionalized biomimetic nanochannels. To get the analogous effect of human ACE2, a receptor for the spike protein, the aptamer to bind to the spike S1 protein has been first screened by a SELEX technique and then immobilized on the previously prepared nanochannels. In the presence of SARS-CoV-2, the changes in steric hindrance and charge density on the surface of the nanochannels will affect the ion transport, along with a rapid electrochemical response. Our method has been successfully applied to detect the viral particles in clinical pharyngeal swab specimens in one step without sample treatment. We expect this rapid, reagent-free, and sensitive assay method to be developed as a useful tool for diagnosing COVID-19.
研究领域:
生物医学工程
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病毒学
·
诊断学
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DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2025
·
IF 2.7
Fei Yuan,Yiyuan Xin,Caifeng Yuan,Zhuo Chen,Tongling Qin,Wenxia Hu,Jiahuan Duan,E Tang
A simple, exogenous-base-free, and NBS-mediated C-selenocyanation/cyclization reaction of enaminones with KSeCN under mild conditions, providing a facile route to 2-aminoselenazole products, has been developed. This efficient protocol is postulated to first undergo the NBS-oxidated polarity reversal of the reactive SeCN- anion to form N-selenocyanosuccinimide as an electrophilic selenium source, which can induce the C-selenocyanation of enaminones and enamino esters, followed by a nucleophilic cyclization promoted by in-situ yielded HBr.
研究领域:
有机化学
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合成化学
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硒化学
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DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2025
·Vol. 22
·期 8
·1773-1790
·
IF 3.2
Xing Shu-Juan,Gao Ying-Feng,Liu Lu,Sui Bing-Dong,Da Ning-Ning,Liu Jin-Yu,Wang Hao,Yuan Yuan,Qin Yuan,Liu Pei-Sheng,Ying Si-Qi,Zhang Kai,Liu Jie-Xi,Chen Ji,Liu Yi-Han,Xie Xin,Jin Yan,Zhang Sha,Zheng Chen-Xi
Background: Type 2 diabetes (T2D) is a global metabolic condition associated with complications of multiple organs, including the bone. However, the exact impact of T2D on bone along the disease progression, particularly in the early phase, remains largely unknown.Methods: Four-week and sixteen-week high-fat diet (HFD) feeding-induced T2D mouse models were established, and the glucose metabolic status was examined. Bone mass was evaluated by micro-computed tomography (micro-CT), and immunofluorescent (IF) staining was performed for bone histomorphometry with enzyme-linked immunosorbent assay (ELISA) determining serum markers. RNA sequencing analysis was performed to examine the transcriptome of bone, and single-cell RNA-sequencing (scRNA-seq) analysis was further applied. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and analyzed for functional behaviors.Results: The occurrence of glucose metabolic disorders was confirmed at both four weeks and sixteen weeks of HFD feeding, showing increased blood glucose levels with impaired glucose tolerance and insulin sensitivity. Notably, early T2D osteoporosis symptoms were detected at four weeks, especially in the trabecular bone, demonstrating reduced bone mass and mineral density. Histological analysis confirmed that bone remodeling and immune-related inflammation were also altered in T2D mice, remarkably at the early phase, mainly reflected by suppressed bone formation, stimulated bone resorption, increased macrophages, and elevated tumor necrosis factor-alpha (TNF-α) levels. Transcriptomic sequencing further demonstrated significant yet distinct changes in the gene expression profile of bone during T2D progression, which confirmed the histological findings. Notably, overlapping genes with altered expression at four weeks and sixteen weeks of T2D compared to the respective control were identified, and bone marrow scRNA-seq analysis indicated many of them were expressed in BMMSCs, suggesting BMMSCs critically involved in T2D osteoporosis. Dysregulated molecular profiles and functional abnormalities of BMMSCs in T2D mice were validated by ex vivo assays, showing early and persistent occurrence of impaired colony-forming and proliferative capacities with biased differentiation potential.Conclusions: These findings elucidate the bone lesion phenotype in T2D, particularly at the early phase, uncover changes in gene expression profiles of bone during T2D progression, and clarify the functional alterations in bone stem cells, providing a basis for subsequent research and the development of treatment strategies.
研究领域:
医学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
LETTERS IN ORGANIC CHEMISTRY
·
2025
·Vol. 22
·期 8
·633-641
·
IF 1
Hongyin Wang,Yu Liang,Yida Yu,Yihao Wang,Ni An,Dong Cai
The ureido moiety stands as one of the most regarded scaffolds in medicinal and organic synthesis. In this study, we endeavored to synthesize a product containing tertiary amine moieties through the nucleophilic substitution reaction of the 2-chloroethyl urea derivative with a secondary amine, utilizing either inorganic bases, such as K2CO3 or organic bases like triethylamine as acid-binding agents in diverse reaction media. Unfortunately, the reaction failed to yield the desired nucleophilic substitution product in high yield, attributed to the reactivity of the 2-chloroethyl urea derivative. The structures of potential impurities were elucidated based on comprehensive spectroscopic data, including 1H NMR, 13C NMR, HRMS, HMBC, and HSQC.
研究领域:
药物化学
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有机合成
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亲核取代反应
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化学反应优化
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产品关联
DOI
高影响因子
JOURNAL OF PHYSICS D-APPLIED PHYSICS
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2022
·Vol. 55
·期 42
·424005
·
IF 3.409
Chang Wang,Ran Duan,Xingcheng Xiao,Yingwei Wang,Zhihui Chen,Yejun Li,Si Xiao,Jun He
Long hexagonal Co3(PO4)2·4H2O nanosheets were synthesized using a hydrothermal method, where their nonlinearity was probed via a femtosecond Z-scan system. The results show that the Co3(PO4)2·4H2O nanosheets exhibit saturable absorption when the incident photon energy is greater than the forbidden band width, while optical limiting is found when the incident photon energy is smaller than the forbidden band width. In particular, the obtained Co3(PO4)2·4H2O nanosheets demonstrate the best optical limiting properties at 600 nm. The present study suggests the cobalt phosphates nanosheets as a promising candidate for optical limiters.
研究领域:
材料科学
·
光学
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DOI
高影响因子
Russian Journal of Physical Chemistry A
·
2019
·Vol. 93
·期 4
·696-702
·
IF 0.581
Huanxin Li,Zhang Haihan,Dou Yonghui,Xu Li,Liu Guoji
Abstract The solubility of (1R,2R)-(+)-1,2-diaminocyclohexane L-tartrate (DHT) in methanol + water, ethanol + water, and 2-propanol + water mixed solvents were measured using a synthetic method with alcohols mass fractions varying from 0.1 to 0.5 over 278.15 to 318.15 K under atmospheric pressure ( P = 0.1 MPa). It was proved that the solubility of DHT in the three binary solvents increased with increasing temperature, while decreased with the mass fraction of alcohols rising. The experimental solubility data were correlated by the modified Apelblat equation and Sun model. The modified Apelblat model showed better agreement with the experimental data than the other model. Furthermore, the thermodynamic parameters including \(\Delta G_{{{\text{sol}}}}^{^\circ }\) , \(\Delta H_{{{\text{sol}}}}^{^\circ }\) , and \(\Delta S_{{{\text{sol}}}}^{^\circ }\) for DHT in the dissolution process were obtained from Van’t Hoff plots.
研究领域:
物理化学
·
药物化学
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DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
·
2021
·Vol. 32
·期 10
·13941-13947
·
IF 2.478
Liu Ying,Cao Bo,Zhang Xu,Luo Rong,Luo Chunhua,Lin Hechun,Peng Hui
Layered Co(OH) 2 has been regarded as a potential candidate for pseudocapacitor electrode material, but it is limited by its poor conductivity and low surface area. Herein, carbonated multi-walled carbon nanotubes (MWCNTs-COOH) were used to improve the conductivity of α-Co(OH) 2 nanocomposites. α-Co(OH) 2 nanoflowers were successfully grown and tangled with MWCNTs-COOH to form a randomly oriented network structure mediated by ammonia using water-methanol as co-solvent at room temperature. The capacitance performances of the obtained α-Co(OH) 2 @MWCNT-COOH composites were investigated to find that MWCNT-COOH improved the specific capacitance efficiently. Especially, in the presence of 20% in mole of MWCNT-COOH, the composite gave rise to the high specific capacitance of 1027 F/g at the current density of 2 A/g with good cycle stability, whose specific capacitance remained 78% of its original even after 5000 cycles at 30 A/g current. The large surface area and strengthening the conductivity of the composites lead to the improvement of efficiency in charge/discharge process.
研究领域:
材料科学
·
能源存储
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2015
·
IF 2.979
Yi Min,Zhigang Sui,Zhen Liang,Lihua Zhang,Yukui Zhang
Superficially porous particles (SPPs) demonstrate superior efficiency than totally porous particles in chiral separations. In order to obtain high efficiency and fast separation, sub-2 μm SPPs with high surface area are synthesized, and with teicoplanin bonded, such materials are successfully applied into the rapid enantioseparation of native amino acids. In brief, 1.27 ± 0.06 μm nonporous silica particles are prepared by a modified seeded growth method, followed by mesoporous shell fabrication via one-pot templated dissolution and redeposition strategy, and pore size expansion via acid-refluxing. The diameter of the formed SPPs is 1.49 ± 0.04 μm, with the shell thickness as 206 nm. Nitrogen physisorption experiments show that the Brunauer–Emmett–Teller (BET) specific surface area is 213.6 m 2 /g and pore size is 9 nm. After teicoplanin derivatization with bonding capacity as 83.3 μmol/g, the prepared chiral stationary phase is packed into a stainless steel tube with the geometry of 50 mm × 2.1 mm i.d.. In less than 6.4 min, six native amino acids (norleucine, alanine, valine, methionine, leucine, norvaline) are enantioseparated with resolution factors ranging from 1.9 to 5.0. Besides, the resolution for chiral separation is improved with ethanol-water instead of methanol-water as the mobile phase. Moreover, the low temperature gives higher resolution, but longer retention time and higher backpressure. Finally, the effect of flow rate on enantiomeric separation is studied and fast chiral separation within 1 min is obtained with flow rate of 0.4 mL/min. All these results show that the synthesized teicoplanin bonded sub-2 μm SPPs have great potential to achieve the enantioseparation of native amino acids with high resolution and rapid speed.
研究领域:
分析化学
·
色谱技术
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DOI
高影响因子
JOURNAL OF NATURAL PRODUCTS
·
2025
·
IF 3.6
Xijian Wu,Zijie Su,Biling Huang,Xin Peng,Xing Zhang,Shaohua Huang
The detection and analysis of chiral molecules have long been challenging in analytical chemistry. This study introduces a novel approach that utilizes 2-trifluoromethyl benzaldehyde as a small-molecule probe capable of forming a stable Schiff base with chiral amino acids in aqueous solution under alkaline conditions. The amino acid Schiff bases present a strong Cotton effect and UV absorption at wavelengths exceeding 260 nm, enabling chiral analysis, including assignment of absolute configuration, enantiomeric composition, and total concentration. An application of this method was the authentication of the herbal medicine Ophiopogon japonicus. Using principal component analysis and orthogonal partial least squares discriminant analysis, we successfully differentiated O. japonicus samples collected in two distinct locations with 20 samples. This rapid and convenient method offers a new approach to quality control of herbal medicine.
研究领域:
分析化学
·
中药学
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DOI
PubMed
高影响因子
JOURNAL OF STRUCTURAL CHEMISTRY
·
2023
·Vol. 64
·期 3
·474-485
·
IF 0.8
Li L.,Yuan F.
Abstract Reaction of H 3 salmp (H 3 salmp = 2-bis(salicylidieneamino)methylphenol) and lanthanide ions has afforded three lanthanide-schiff base complexes. One is homodinuclear [Nd(Hsalmp)(NO 3 )(EtOH)] 2 ·2EtOH ( 1 ), other two are heteroleptic tetranuclear [LnNa(salmp)(sal)(EtOH) 3 ] 2 (Ln = Nd ( 2 ), Ce ( 3 ); sal = salicylaldehydato) architectures. In complex 1 , the counter Hsalmp 2– anions adopt NO 3 donor sets, wheras in complexes 2 and 3 , the counter salmp 3– anions select N 2 O 3 donor sets and sal – anions chose O 2 donor sets, in which cleavage of C=N groups in ligand has taken place. The amount of alkali has displayed a vital influence on preparation of these complexes. Both of the complexes were elucidated by elemental analysis, IR, fluorescence spectra and X-ray crystallography.
研究领域:
化学
·
配位化学
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DOI
高影响因子
危险品化学品经营许可证（带存储）