Journal of Materials Chemistry B
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2017
·Vol. 5
·期 20
·3728-3738
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IF 4.543
Tong Liu,Ruiying Huang,Juchang Zhong,Yikun Yang,Zhikai Tan,Weihong Tan
The ideal 3D scaffold for biological applications has not yet been designed. Our aim is to better match the scaffold performance through fine control of the fabrication process. Here, we applied electro-hydrodynamic jet (E-jet) 3D printing technology using poly-(lactic-co-glycolic acid) (PLGA) solution to construct scaffolds for tissue engineering applications. We fabricated different scaffolds of 1 : 1, 1 : 2 and 1 : 3 aspect ratios and tested the biological compatibility of the 2D and 3D printed scaffolds with fibroblasts. The scaffolds were used to culture fibroblasts, the main cellular components of loose connective tissue. The results show that the E-jet printed scaffolds could guide and improve cell growth. These scaffolds were able to support cellular alignment and proliferation. The cell angle was consistent with the longitudinal direction of the scaffolds, potentially enhancing the wound healing performance. Thus, the potential of this flexible technology for the 3D printing of scaffolds for the engineering of tissues is extensive.
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JOURNAL OF NANOPARTICLE RESEARCH
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2014
·Vol. 16
·期 4
·1-16
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IF 2.278
Lian He,Zhang Tianhong,Sun Jin,Pu Xiaohui,Tang Yilin,Zhang Youxi,He Zhonggui
The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan–vitamin E succinate– N -acetyl- l -cysteine (CS–VES–NAC) nanomicelles from the cellular level. In aqueous solution, CS–VES–NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS–VES–NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS–VES–NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS–VES–NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P
app value of PTX-loaded CS–VES–NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS–VES–NAC copolymer, the P
app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS–VES–NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.
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MOLECULAR PHARMACEUTICS
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2013
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IF 4.57
He Lian,Tianhong Zhang,Jin Sun,Xiaohong Liu,Guolian Ren,Longfa Kou,Youxi Zhang,Xiaopeng Han,Wenya Ding,Xiaoyu Ai,Chunnuan Wu,Lin Li,Yongjun Wang,Yinghua Sun,Siling Wang,Zhonggui He
In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min–1, Papp = 0.059 cm·min–1) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0–t (586.37 ng/mL·h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.
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JOURNAL OF BIOTECHNOLOGY
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2015
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IF 2.871
Yue-De Cao,Yu-Cai He,Hao Li,Guo-Yin Kai,Jian-He Xu,Hui-Lei Yu
Hyoscyamine 6 β -hydroxylase (H6H, EC 1.14.11.11), an α-ketoglutarate dependent dioxygenase catalyzes the hydroxylation of (−)-hyoscyamine and the subsequent epoxidation of 6 β -hydroxyhyoscyamine to form scopolamine, a valuable natural alkaloid. In this study, random mutagenesis and site-directed saturation mutagenesis were used to enhance the hydroxylation activity of H6H from Anisodus acutangulus ( Aa H6H). A double mutant, Aa H6H M1 (S14P/K97A), showed a 3.4-fold improved hydroxylation activity compared with the wild-type enzyme, and the in vivo epoxidation activity was also improved by 2.3 times. After 34 h cultivation of Escherichia coli cells harboring Aa h6h m1 in a 5-L bioreactor with a working volume of 3 L, scopolamine was produced via a single-enzyme-mediated two-step transformation from 500 mg L −1 (−)-hyoscyamine in 97% conversion, and 1.068 g of the product were isolated, corresponding to a space-time yield of 251 mg L −1 d −1 . This study shows that the protein engineering of some key enzymes is a promising and effective way for improving the production of rare natural products such as scopolamine.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
·
IF 2.2
Youming Shi,Wenjiao Gu,Yujie Wei,Shuangyi Li,Shining Zhang,Ying jiang,Chuanjian Chen,Ting Liu,Limei Shuai,Xiaochun Zhou,Futian Tang
Purpose Atherosclerosis (AS) and atherosclerotic calcification (AC) are closely related to the cardiovascular diseases, largely due to its induction of vasomotor dysfunction. We previously reported that Calpain-1 inhibitor attenuated AS and AC. The present study was designed to investigate the effects and potential mechanisms of Calpain-1 knockout (Calpain-1 KO) in Apolipoprotein E KO (ApoE KO) mice on AS, AC, aortic vasomotor function as well as the liver dysfunction. Methods We hybridized ApoE KO mice with Calpain-1 KO mice to obtain ApoE /Calpain-1 double KO (A×C DKO) mice. The formation of AS and AC was evaluated and liver function was determined. Aortic vasomotor function was assessed. Contents of TNF-α, IL-6, IL-18, IL-1β and NO and the activity of AST, ALT, ALP and eNOS in serum were quantified. The mRNA expression of CD68, SR-A, CD36, PPAR-γ, LXR-α, ABCA1, BMP-2, OPN, ALP and Runx2 in aorta and/or liver were measured. Results The results showed that in comparison to C57 mice, ApoE KO mice demonstrated the significant increases in the areas of AS and AC, the increases in the mRNA expression of CD68 in the aorta, the increases in the AST, ALT and ALP activity in serum. ApoE KO mice also showed the dysfunction of the aortic contraction induced by phenylephrine and of the relaxation induced by acetylcholine. However, compared with ApoE KO mice, A×C DKO mice exhibited the significant attenuation of AS and AC and the downregulation of mRNA expression of CD68 in aorta. A×C DKO mice revealed the reduction of AST, ALT and ALP activity in serum, the improvements in aortic contraction and relaxation as well as the increases in eNOS activity and NO content in serum. A×C DKO mice also showed the decreases in the contents of TNF-α, IL-6, IL-18 and IL-1β in serum. The mRNA expression of CD68 in aorta, SR-A and CD36 in both aorta and liver of A×C DKO mice was downregulated, while that of PPAR-γ, LXR-α, and ABCA1 was upregulated in comparison of ApoE KO mice. In addition, the mRNA expression of BMP-2, OPN, ALP and Runx2 in aorta of A×C DKO mice was downregulated in comparison of ApoE KO mice. Conclusion The results suggested that deficiency of Calpain-1 attenuated the formation of AS and AC and improved vasomotor and liver dysfunction in ApoE KO mice through anti-inflammation, and modulation of the mRNA expression of genes related to AS and AC.
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ANALYTICA CHIMICA ACTA
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2024
·
IF 5.7
Zesen Zuo,Kai Liu,Chunqiong Wang,Shengbao He,Fei Yang,Fengqin Chang,Wen-Tong Chen,Guangzhi Hu
Background The heavy metal ion Cd 2+ is acutely toxic, and excessive concentrations can have adverse effects on human production and life, and even lead to significant public health risks and environmental impacts. There are several mature non-electrochemical methods for heavy metal detection, but these methods are characterized by high cost, which makes it difficult to be applied to the field for timely detection. Therefore, it is necessary to prepare a new electrochemical sensor that is environmentally friendly and capable of detecting Cd 2+ in the environment quickly, easily and sensitively. Results In this study, hydrogen-bonded organic frameworks (HOFs) were synthesized by a simple hydrothermal reaction. The prepared materials consisted of only C, N and O and had a thin lamellar structure. The HOFs were integrated into a novel electrochemical sensor to achieve accurate detection of Cd 2+ ions in real aqueous environments by square wave anodic dissolution voltammetry. The sensor has a wide linear range and a detection limit as low as 0.13 μg/L. Several real water samples, such as tap water, lake water, and e-cigarette digest, were analyzed to simulate the working environment of the sensor, and the results showed that the recoveries of Cd 2+ ranged from 95.75 % to 101.2 %. Significance We pioneered the detection of heavy metal ions Cd 2+ in e-cigarette digestate samples with the innovative use of HOFs as the sensor material, which demonstrated the potential application in electrochemical sensing with extremely low background current value and high sensitivity, providing new ideas for environmental monitoring and public health control.
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DRUG DELIVERY
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2017
·
IF 6.402
Huiyun Zhang,Wenqian Xu,Emmanuel Omari-Siaw,Yingkun Liu,Baoding Chen,Deyu Chen,Jiangnan Yu,Ximing Xu
Periplocymarin (PPM), a cardiac glycoside, has a narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity which hinder its wide clinical applications in cancer treatment. Herein, we report novel redox-responsive prodrug-nanoparticles (MPSSV-NPs) self-assembled by co-nanoprecipitation of PPM-vitamin E conjugate and a PEG derivative of linoleate (mPEG2000-LA) in water. It was found that the characteristics of PPM-vitamin E nanoparticles (PSSV-NPs) were improved through co-nanoprecipitation with increased percentages of mPEG2000-LA. Moreover, the MPSSV-NPs were optimized according to the in vitro release and cytotoxicity study. Furthermore, the optimized MPSSV-NPs dramatically enhanced the circulation time and tumor distribution of PSSV-NPs after single intravenous injection. The in vivo studies in malignant H22-bearing mice revealed that MPSSV-NPs could effectively suppress tumor growth without causing obvious systemic toxicity. Altogether, these results suggested that MPSSV-NPs could offer a safe, multifunctional and viable nanoplatform for cardiac glycosides in cancer treatment.
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REACTIVE & FUNCTIONAL POLYMERS
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2024
·
IF 4.5
Zheng Cao,Han Wu,Mengxiao Yang,Zhen Li,Xin Chen,Lin Liu
It is a high demand but a great challenge to construct all-in-one ionic conductive hydrogels with excellent mechanical performances, transparency, self-adhesion, conductivity and environmental tolerance. Herein, a versatile gel platform was developed via a facile and rapid photopolymerization of acrylic acid (AA) in deep eutectic solvent (DES) with multiple roles simultaneously as water-free solvent, ionic conductor , regulator of hydrogen bond density. Benefiting from the formed crosslinking networks including covalently cross-linked polymer network and multiple dynamic interactions, the resultant PAA-DES gels exhibited high stretchability of 884.7 ± 4.9%, toughness of 31.2 ± 1.4 MJ/m 3 , fatigue resistance and recovery ability, transparency of 93%, self-adhesive strength of 472 kPa. Moreover, the inherent advantages of DES enabled the gels with good ionic conductivity (2.5 ± 0.2 mS/cm), wide working window and biocompatibility . The PAA-DES as self-adhesive ionic sensors not only possessed wide strain range (∼400%) and stability, but also displayed excellent humidity (30–80%), temperature (−40–60 °C), and sweat tolerance which could precisely and steadily discern and monitor human motions and weak physiological signals. Thus, this work not only provides a strategy to construct all-in-one ionic conductive gels with high elasticity, fatigue resilience, transparency, self-adhesion and wide environmental tolerance, but also exploits versatile platform for intelligent gel sensor and e-skin.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Qian Zhang,Xudong Lü,Yuanyuan Jin,Mengjia Tang,Miao Wang,Sen Zou,Shuai Fan,Zhaoyong Yang
Cyst(e)inase, an engineered human cystathionine-γ-lyase (hCGL), effectively degrades l-Cys and CSSC, inhibiting various tumors in vivo with minimal toxicity. However, its current activity and stability limit its clinical application. To enhance its therapeutic potential, we utilized folding free energy calculations and amino acid site conservation to identify 46 potential mutants. Among them, 17 mutants exhibited improved activity or stability, while six showed a loss of function. Notably, mutant L142E enhanced activity for both substrates, and E349S displayed 2.8 times higher activity toward CSSC and a 12.8 °C increase in Tm, despite reduced activity toward l-Cys. Saturation mutagenesis highlighted the importance of spatial constraints for substrate selectivity. MD simulations suggested that distal mutations stabilize the near-attack conformation, enhancing the activity. In vitro cytotoxicity assays confirmed that the mutants L142E and E349S significantly inhibited gastric and pancreatic cancer cells. This study provides valuable insights for improving therapeutic enzyme design.
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Food Bioscience
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2024
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IF 4.8
Chenghui Zhang,Changzhu Li,Tariq Aziz,Metab Alharbi,Haiying Cui,Lin Lin
Food processing environments contaminated with E. coli O157 :H7 and forming biofilms will be a continuous source of contamination, leading to foodborne illness and food spoilage. Now, the main countermeasure is chemical disinfectants, but the use of disinfectants may cause the development of drug-resistant bacteria and other negative effects. Therefore, there is an urgent need to find novel antimicrobial agents. Quorum-sensing inhibitors (QSI) are a promising strategy to control biofilm formation. This study aimed to screen the optimal QSI of E. coli O157 :H7 from plant-derived small molecules by biofilm and QS inhibitory activities and to validate their effectiveness in combination with disinfectants. In addition, the inhibition mechanism of gallic acid on biofilm formation was further explored. Gallic acid was screened as the QSI of E. coli O157 :H7, and its AI-2 inhibitory activity against LuxS/AI-2 QS system reached 95.54% and 98.89% after treatment with 1/2 MIC gallic acid for 4 h and 6 h, respectively. It inhibited biofilm formation by affecting flagellar assembly, chemotaxis, and expression of adhesion factor-related genes, which interfered with the transition of bacteria from reversible to irreversible adhesion. In beef broth simulation system, the inhibition rate was greater than 90.00% in all gallic acid and benzalkonium chloride combination groups. Therefore, gallic acid can be a potential antimicrobial synergist in the food industry, combined with disinfectants to control E. coli O157 :H7 biofilms while avoiding the development of resistance.
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ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Xuan Sun,Yu Wang,Lu Zhang,Sha Liu,Man Zhang,Jiang Wang,Baoan Ning,Yuan Peng,Jing He,Yonggang Hu,Zhixian Gao
Escherichia coli O157:H7 has been reported as an important pathogenic bacteria causing serious infection and economic loss. However, detection of Escherichia coli O157:H7 needs improvement, given its current complexity and sensitivity. Herein, we attempt to build a fluorescence sensing method to detect Escherichia coli O157:H7 with easy operation and high efficiency. The target virulence gene sequences are recognized and cleaved by the CRISPR-Cas9 system, and trigger strand displacement amplification and rolling circle amplification. After amplification reactions, massive products can hybridize with the probes, the fluorescence of which are quenched based on a metal–organic framework platform, leading to the fluorescence recovery at typical excitation/emission wavelengths of 480/518 nm. This method exhibits high sensitivity with the detection limit at 4.0 × 101 CFU mL–1 and a wide range from 1.3 × 102 CFU mL–1 to 6.5 × 104 CFU mL–1. Meanwhile, this assay also shows significant specificity and applies to practical samples with high accuracy. Therefore, our method would have great potential application in bacterial detection, food safety monitoring, or clinical diagnostics.
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Food Bioscience
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2025
·
IF 5.9
Fei Teng,Xixi Wu,Yue Liu,Lijia Li,Mengjie Geng
Emulsion gel is widely used in the delivery of functional components because of its network structure and mechanical properties. In this study, to improve the structural and functional properties of emulsion gels and achieve efficient encapsulation and release of functional components, transglutaminase (TGase) and genipin were employed to crosslink pH-shifting/ultrasonication-modified soybean lipophilic protein (SLP), enabling the simultaneous encapsulation of vitamin E (VE, oil phase) and quercetin (QU, aqueous phase), thereby developing a co-encapsulated emulsion gel system. The impacts of combined modification (pH-ultrasonication) and enzymatic/chemical crosslinking on gel properties were systematically investigated through gel strength analysis, rheological characterization, intermolecular interaction profiling, microstructural observation, and in vitro digestion evaluation. Results demonstrated that pH-shifting combined with ultrasonication exposed more hydrophobic groups in SLP, thereby enhancing intermolecular hydrophobic interactions. Microstructural analysis revealed that TGase and genipin synergistically strengthened network crosslinking density, forming a more compact gel network structure under modified conditions. Furthermore, TGase/genipin crosslinking significantly improved structural characteristics and rheological performance (e.g., water-holding capacity increased by 14.97 %, hardness and viscosity improved), while concurrently enhancing encapsulation efficiencies of both VE and QU. In vitro digestion test confirmed that the maximum release rate reached 97.43 ± 1.50 % (VE) and 90.39 ± 2.43 % (QU) ( p < 0.05). These findings elucidated the potential for constructing emulsion gels via combined modification and crosslinking strategies, providing theoretical guidance for co-encapsulation systems in functional factors delivery applications.
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