Acta Biomaterialia
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2021
·
IF 8.947
Wenjuan Huang,Sijie Zhou,Bojiao Tang,Hongyan Xu,Xiaoxiao Wu,Na Li,Xingjie Zan,Wujun Geng
Proteins play key roles in most biological processes , and protein dysfunction can cause various diseases. Over the past few decades, tremendous development has occurred in the protein therapeutic market due to the high specificity, low side effects, and low risk of proteins. Currently, all protein drugs on the market are based on extracellular targeting; more than 70% of intracellular targets remain un-druggable. Efficient delivery of cytosolic proteins is of significance for protein drugs, advanced biotechnology and molecular cell biology. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for intracellular protein delivery. Based on the coordinative interaction between His 6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged protein encapsulation particles( [email protected] ) through a co-assembly process with a high loading capacity and loading efficiency. [email protected] was able to deliver proteins with diverse physicochemical properties through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. Our results demonstrate that this strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics. Statement of significance Intracellular targets with protein drugs may provide a new way for the treatment of many refractory disease. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for efficient intracellular protein delivery. Based on the coordinative interaction between His 6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged particles ( [email protected] ) with a high loading efficiency. [email protected] was able to deliver different proteins through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. This strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics.
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Food & Function
·
2021
·Vol. 12
·期 15
·7054-7067
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IF 5.396
Caixin Ni,Xin Li,Linlin Wang,Xiu Li,Jianxin Zhao,Hao Zhang,Gang Wang,Wei Chen
Globally, the incidence of hyperuricaemia is steadily increasing. The evidence increasingly suggests an association between hyperuricaemia and the gut microbiota, which may enable the development of a novel therapeutic approach. We studied the effects of treatment with lactic acid bacteria (LAB) on hyperuricaemia and their potential underlying mechanisms. A mouse model of hyperuricaemia was generated by oral gavage with hypoxanthine and intraperitoneal injections of potassium oxonate for 2 weeks. The anti-hyperuricaemic activities of 10 LAB strains relative to allopurinol as a positive drug control were investigated in the mouse model. Lactobacillus rhamnosus R31, L. rhamnosus R28-1 and L. reuteri L20M3 effectively reduced the uric acid (UA) concentrations in serum and urine and the xanthine oxidase (XOD) activity levels in serum and hepatic tissue in mice with hyperuricaemia. These strains also reversed the elevated lipopolysaccharide (LPS) concentration, hepatic inflammation and slight renal injury associated with hyperuricaemia. A correlation analysis revealed that UA-reducing LAB strains promoted short-chain fatty acid (SCFA) production to suppress serum and hepatic XOD activity by increasing the abundances of SCFA production-related gut bacterial taxa. However, the UA-reducing effects of LAB strains might not be mediated by purine degradation. In summary, L. rhamnosus R31, L. rhamnosus R28-1 and L. reuteri L20M3 relieved hyperuricaemia in our mouse model by promoting SCFA production in a purine degradation-independent manner. Our findings suggest a novel therapeutic approach involving LAB strains for hyperuricaemia.
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ELECTROPHORESIS
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2021
·
IF 3.535
Hui Jiang,Hao Zhang,Shi-Jun Yin,Min Lu,Xu Wang,Feng-Qing Yang
Profiling of lipid–water partition coefficients ( K L/W ) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid–water partition coefficients (log K L/W ) of neutral and ionic drugs were determined based on an iterative method. The log K L/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient ( R 2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol–water system, immobilized artificial membrane, Caco-2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco-2 cell model, and R 2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J – were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log K L/W of drugs.
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MICROCHEMICAL JOURNAL
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2020
·
IF 3.594
Xiaojing Zhang,Yanying Wang,Hongping Deng,Xiaoxing Xiong,Huijuan Zhang,Tao Liang,Chunya Li
CA125 is the most widely used biomarker for the early detection of ovarian cancer. Luminescence resonance energy transfer (LRET)-based probes show pronounced specificity and simplicity for CA125 detection, but they suffer from strong interference from autofluorescence of biosamples. To resolve this problem, near-infrared (NIR)-excitable upconversion nanoparticles (UCNPs) was employed as energy donor to fabricate CA125 biosensor. Carbon dots (CDs) were utilized as energy acceptor for the overlap between the upconversion luminescence (UCL) spectrum of UCNPs and the absorption spectrum of CDs. Aptamer-modified UCNPs were combined with CDs through π-π stacking interaction, which triggered the LRET process and induce UCL quenching with a high quenching efficiency of up to 90%. In presence of CA125, the formation of CA125-aptamer complex blocked the π-π stacking and recovered UCL. The UCL intensity increased linearly with the logarithm of CA125 concentration in the range from 0.01 to 100 U·mL −1 . A detection limit of 9.0 × 10 −3 U·mL −1 was obtained. This probe is also available for CA125 detection in human serum and may be a useful tool for the early detection of ovarian cancer.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Jinxu Qiu,Boran Chen,Hongying Hou,Xiaojuan Wang,Xiaoyang Liu,Zaihuan Li,Tingting Liu,Ruicong Chen,Shuai Wang,Bao Li,Dongmei Dai,Bao Wang
Because of their high reversible capacity and wide operation voltage window, P2-type layered transition metal oxides are considered as one type of potential cathode candidate for sodium-ion batteries. However, they still suffer from low kinetics, phase degeneration, and ambiguous mechanism of Na+ diffusion. Here, we synthesized a P2-type Na0.6Li0.07Mn0.66Co0.17Ni0.17O2 with a high Na+ diffusion performance by sintering a nanoplate-structural precursor with alkali metal salt and proposed a possible mechanism for improving Na+ diffusion. The as-prepared P2-type layered oxide presents a quasi-hexagon shape and demonstrates a discharge capacity of 87 mAh g–1 at a current density of 875 mA g–1 (5 C rate), twice that of the sample synthesized from a non-nanoplate particle precursor. Rietveld refinement and results of X-ray photoelectron spectroscopy reveal the probable mechanism that the expanded interplanar spacing along the c-axis orientation would facilitate Na+ diffusion during Na+ intercalation/deintercalation processes, and the expanded interplanar spacing may arise from a high oxidation state of transition metal ions.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2020
·
IF 5.774
Jinchao Fang,Ge Liu,Cheng Chen,Chuner Lin,Bin Zhang,Huiyang Jin,Yuji Chen,Jingyu Lu,Liping Zhu
Biofouling is a pervasive and crucial issue in membrane separation processes, as it leads to the deterioration in separation efficiency. To address this issue, the antibacterial membrane with high biofouling resistance is in urgent demand, what has been remained challenging. In this work, an intrinsically antibacterial thin film composite (TFC) membranes was prepared using supramolecularly assembled lysozyme (SAL) nanofilm as a selective layer. The nanofilms were achieved by depositing onto a hydrolyzed polyacrylonitrile (h-PAN) support membrane using phase transition and aggregation of lysozyme from its aqueous solution. The prepared membranes showed a high rejection ratio towards vitamin B 12 (95.3%) with a water permeation flux of 48.6 L·m −2 ·h −1 under 0.4 MPa, showing great potential in the molecular separation. Furthermore, the antibacterial efficiencies of the typical membrane toward E. coli and S. aureus reached 93.2% and 92.2%, respectively, indicating that the SAL selective layer can effectively resist bacterial adhesion and reproduction on the membrane surface. This work provides an innovative strategy and insight in fabricating the high-performance antibacterial TFC membranes for aqueous molecular separation via protein supramolecular assembly.
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PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
·
2020
·Vol. 19
·期 4
·485-494
·
IF 2.831
Ma Wenpeng,Liu Chengcheng,Li Jiao,Hao Ming,Ji Yanhong,Zeng Xiaoyan
The extensive and repetitive use of antifungal drugs has led to the development of drug-resistant Candida albicans . Antimicrobial photodynamic therapy (aPDT) has received considerable attention as an emerging and promising approach to combat drug-resistant microbes. This study evaluated the photodynamic effects mediated by aloe emodin (AE), a natural compound isolated from Aloe vera and Rheum palmatum, on azole-sensitive and azole-resistant C. albicans in vitro . AE exhibited no significant dark toxicity, but in the presence of light, effectively inactivated C. albicans cells in a concentration-dependent manner. The uptake of AE by fungal cells was investigated by confocal laser scanning microscopy (CLSM), and the results showed that AE possessed stronger ability to enter into C. albicans cells following light irradiation. Transmission electron microscopy analysis suggested that AE-mediated aPDT could induce damage to the cell wall, cytoplasm, and nucleus. Damage to the surface of C. albicans was observed by scanning electron microscopy. These results suggest that AE is a potential PS for use in aPDT of drug-resistant C. albicans strains, and AE-mediated aPDT shows promise as an antifungal treatment.
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GREEN CHEMISTRY
·
2020
·Vol. 22
·期 19
·6579-6587
·
IF 9.48
Xiaohao Liu,Xiaodong Liu,Haiyong Wang,Tianci Xiao,Ying Zhang,Longlong Ma
Efficient conversion of renewable cellulose to high value-added C3 chemicals is a great challenge in the field of biomass valorization. In this work, we found that the combination of Co and Sn could significantly improve the efficiency of cellulose conversion to acetol. 54.4% yield of acetol and 66.6% total yield of C3 products were obtained when using 2%Sn–10%Co/SiO2 (2 wt% Sn content) as a catalyst. However, using the same Sn content of 2%Sn–10%Ni/SiO2, no acetol and only 7.1% yield of C3 products were produced. By studying the effects of different Sn and Co concentrations on cellulose conversion, it was found that the Sn species play an important role in catalyzing glucose conversion to C3 intermediates, while Co mainly played a role in hydrogenation, the same as Ni. The study demonstrated that Sn–Co/SiO2 with low Sn content can convert glucose to C3 intermediates more efficiently than the Sn–Ni/SiO2 catalyst. Moreover, Sn–Co/SiO2 could effectively convert C3 intermediates to acetol at a high temperature which is essential for acetol production from cellulose; but under the same conditions, the Sn–Ni/SiO2 catalyst tended to catalyze the polymerization of C3 intermediates. A series of characterization methods including AAS, TEM, HRTEM, EDS, XRD, ex situ XPS, in situ XPS, and CO2-TPD found that the combination of Sn and Co could significantly increase the noninteger valent SnOx species in the catalyst. These species increased the basicity of the catalyst and were beneficial in catalyzing the isomerization of glucose and the retro-aldol condensation of fructose.
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ACS Catalysis
·
2020
·
IF 12.35
Haiyong Wang,Haosheng Xin,Chiliu Cai,Changhui Zhu,Zhongxun Xiu,Qiying Liu,Yujing Weng,Chenguang Wang,Xinghua Zhang,Shijun Liu,Zifang Peng,Longlong Ma
Keto-alcohols, which are traditionally produced from fossil resources with multisteps, are considered as important intermediates for diversified high-value-added fine chemical synthesis due to their involved carbonyl and hydroxyl groups. Herein, direct cellulose hydrogenolysis to C3-C4 keto-alcohol products (hydroxyacetone and 1(3)-hydroxy-2-butanone) was achieved over Ni-WOx/C catalysts with an W/Ni atom ratio of 1.0–5.0. The keto-alcohol yield was proposed to strongly depend on the W/Ni ratio and the catalyst annealing temperature. The highest keto-alcohol yield of 63% was obtained at the optimal balance of basic/acidic WOx species and metallic Ni. The introduction of Ni facilitated the formation of the basic W5+ sites, which enhanced the formation of basic sites at the Ni-WOx interface. The synergistic effect between the basic W5+ and acidic oxygen vacancy (Vö) could activate the target C–O/C═O bonds, promoting the isomerization of glucose and C3-C4 aldehyde intermediates with the assistance of the interfacial Ni. The cooperative adsorption of the −OH and −C═O groups at the Ni-O-W-Vö interface stabilized the adjacent ketone and hydroxyl groups and kept the other hydroxyl groups for hydrogenolysis, obtaining the final C3-C4 keto-alcohols. This work expanded the application of cellulosic biomass, enabling the green and sustainable synthesis of the high-value C3-C4 keto-alcohol products using lignocellulosic biomass as a raw material.
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JOURNAL OF INORGANIC BIOCHEMISTRY
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2021
·
IF 4.155
Yucui Jiang,Saixing Liu,Qipeng Yuan,Hao Liang
Acidophilic enzymes play an important role in special industrial catalytic reactions. In this work, we reported Zr-based acid-stable nucleotide coordination polymers (CPs) for efficiently improving acidophilic enzymes immobilization . Among all tested metal ions , the Zr 4+ /AMP CPs exhibited the highest acid stability and enzyme affinity. As a typical acidophilic enzyme, the immobilized Chloroperoxidase by Zr 4+ /AMP CPs displayed robust reusability in the asymmetric synthesis of modafinil, remained 95.7% of conversion rate and 99.1% enantiomeric excess (e.e.) value. This work displayed a novel acid-stable bioorganic and inorganic hybrid nanomaterial for acidophilic enzymes immobilization.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Peiqi Luo,Liping Wang,Lixia Jiang,Jie Sun,Yafeng Li,Huihui Liu,Caiqiao Xiong,Zongxiu Nie
Graphdiyne (GD) is a new kind of carbon nanomaterial which has carbon–carbon triple bonds to form a layered structure. Here, we report the application of GD as the matrix for small molecule analysis in laser desorption ionization mass spectrometry (LDI MS). The GD matrix displayed two advantages: little background in the low mass range and good molecular ion signal in negative ion mode for many small molecules, e.g., fatty acids, amino acids, peptides, and drugs can be obtained in negative ion mode. By comparing the signal intensity of tetraphenylborate and juglone with and without GD existing, it was found that GD can enhance both of the desorption efficiency and ionization efficiency in LDI. Through analysis of the serum samples from liver cancer patients and healthy people, the GD-assisted LDI MS results showed that fatty acids could be used as potential biomarkers for the early diagnosis of liver cancer.
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JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 44
·期 5
·954-962
·
IF 2.878
Lu Kang,Ju Liu,Hongyang Zhang,Min Jiang,Yidian Jin,Min Zhang,Ping Hu
Creatinine and purines are gout-related metabolites commonly quantified by liquid chromatography coupled with ultraviolet and mass spectrometry. However, the high cost of liquid chromatography coupled with mass spectrometry hindered its extensive use in ordinary hospitals and clinical laboratories. Using the traditional liquid chromatography method, the full separation of these metabolites in complex biological samples is still not achieved. In this study, an improved ultra-high-performance liquid chromatography with ultraviolet spectroscopy method was reported for quantitative determination of five gout-related metabolites (i.e., creatinine, uric acid, hypoxanthine, xanthine, and inosine) in human serum within 10 min. A UHPLC system equipped with a hydrophilic C18 column was used to improve separation, shorten analysis time, and increase analysis throughput. The performance of the method was validated by evaluating linearity (squared correlation coefficient > 0.9991), recovery (92.8–100.0%, with relative standard deviation < 4.7%), accuracy (relative errors < 14.6%), precision (0.2-4.1% for intraday and 2.1-7.3% for interday) and stability (-14.1 to 8.3% in autosampler for 12 h and -13.3 to 2.2% for freeze-thaw cycles). This method was successfully applied to quantify gout-related metabolites in serum samples of healthy controls and gout patients, which was expected to be used in the clinical investigation of gout at different stages.
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