Frontiers in Bioengineering and Biotechnology
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2022
·
IF 6.064
Tong Feifei,Qin Zongmin,Wang Hongyue,Jiang Yingying,Li Junkuan,Ming Hui,Qu Ge,Xiao Yazhong,Sun Zhoutong
Chiral amino alcohols are prevalent synthons in pharmaceuticals and synthetic bioactive compounds. The efficient synthesis of chiral amino alcohols using ammonia as the sole amino donor under mild conditions is highly desired and challenging in organic chemistry and biotechnology. Our previous work explored a panel of engineered amine dehydrogenases (AmDHs) derived from amino acid dehydrogenase (AADH), enabling the one-step synthesis of chiral amino alcohols via the asymmetric reductive amination of α-hydroxy ketones. Although the AmDH-directed asymmetric reduction is in a high stereoselective manner, the activity is yet fully excavated. Herein, an engineered AmDH derived from a leucine dehydrogenase from Sporosarcina psychrophila (SpAmDH) was recruited as the starting enzyme, and the combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was applied to improve the activity. After three rounds of mutagenesis in an iterative fashion, the best variant wh84 was obtained and proved to be effective in the asymmetric reductive amination of 1-hydroxy-2-butanone with 4-fold improvements in kcat/Km and total turnover number (TTN) values compared to those of the starting enzyme, while maintaining high enantioselectivity (ee >99%) and thermostability (T5015 >53°C). In preparative-scale reaction, the conversion of 100 and 200 mM 1-hydroxy-2-butanone catalyzed by wh84 was up to 91–99%. Insights into the source of an enhanced activity were gained by the computational analysis. Our work expands the catalytic repertoire and toolbox of AmDHs.
研究领域:
生物催化
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酶工程
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有机化学
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生物技术
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高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2020
·
IF 4.352
Yan Wang,Meiling Lian,Xiaoyu Xiu,Zhiwen Zhang,Liping Song,Shengzhou Wu
Metabolism of β-amyloid is critical for healthy brain. Decreased clearance of β-amyloid is associated with ensued accumulation of amyloid peptide, culminating in formation of senile plaques, a neuropathological hallmark of Alzheimer's disease(AD). Apolipoprotein E ( APOE ), a lipoprotein for phospholipid and cholesterol metabolism, is predominantly synthesized by glia in the central nervous system, controlling Aβ aggregation and metabolism. By use of stereotactic injection and a Morris water maze, we found that delivery of Dicer1-expressing adenovirus into the hippocampus of an animal model of AD mice APPswe/PSEN1deltaE9 significantly improved spatial memory. The effect was associated with reduced amyloid peptides in the hippocampus which were analyzed with immunofluorescence and enzyme-linked immunosorbent assay. With western blot, quantitative real-time PCR, fluorescence in situ hybridization, and northern blot,Dicer1 overexpression increased apolipoprotein E (APOE) and concomitantly decreased B2 RNA in the hippocampus of the AD mice and in astrocyte cultures whereas transfection of B2 Mm2 RNA decreased APOE mRNA and protein levels in astrocyte cultures. Further, human or mouse APOE mRNA was found containing Alu RNA or its equivalent, B2 Mm2 RNA, locating downstream of its 3′-untranslated region (UTR), respectively. The 3′-UTR or 3′-UTR in conjunction with the downstream Alu/B2 RNA were cloned into a luciferase reporter; with dual-luciferase assay, we found that simultaneous transfection of Dicer1 siRNA or Alu/B2 RNA decreased the corresponding luciferase activities which suggest that Alu RNA mediated APOE mRNA degradation. Altogether, Dicer1 expression mediated amyloid peptide clearance by increasing APOE via blocking B2 RNA-mediated APOE mRNA degradation.
研究领域:
神经科学
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分子生物学
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神经退行性疾病
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基因调控
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ACS Sustainable Chemistry & Engineering
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2015
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IF 4.642
Lei Qin,Jianan Zhang,Hongye Cheng,Lifang Chen,Zhiwen Qi,Weikang Yuan
Deodorizer distillate as a byproduct of vegetable oil refining is an important source of natural vitamin E. Simple and green extraction can be employed to recover vitamin E from deodorizer distillate, and its performance strongly relies on the solvent used in the process. In order to screen an imidazolium-based ionic liquid (IL) as entrainer, a methodology integrating theoretical and experimental evaluations was applied. ILs composed of 47 types of anions were first investigated by COSMO-RS to figure out the most promising one, and the effect of the alkyl chain on the imidazolium ring was addressed by experiments. The IL [C6MIm]Ac was finally determined as the most promising solvent with the selectivity of 108.23 and the partition coefficient of 8.182 for α-tocopherol. The liquid–liquid equilibrium data and the extraction result for corn oil deodorizer distillate indicate its superior performance for the extraction process dealing with a low concentration of vitamin E.
研究领域:
分离科学
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绿色化学
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生物化工
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离子液体
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天然产物提取
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Advanced Materials Technologies
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2022
·Vol. 7
·期 12
·2200371
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IF 8.856
MingYang Yang,Guangyou Liu,Zheng Zeng,Shuhao Zhang,Jie Liu,Zong Qin,Zhihe Chen,Bo-Ru Yang
Human–machine interaction will be revolutionarily different in the future Internet of Things (IoT) environments. Many displays will be adopted onto electronic devices to enhance human–device communication, even under a very bright sunlight ambience. Thus, power consumption and sunlight visibility are important attributes for this application. Electrophoretic displays (EPDs) have the inherent advantages of ultra-low power consumption and high sunlight visibility, which are perfectly suitable for IoT applications. The low power consumption resulted from the balance of viscosity, gravity, and other complicated forces involved in the electrophoretic dispersion. This force balance is generally termed “bistability,” meaning the particle-packing can be stable without external power at black and white image states. However, good bistability implies a slow image updating rate, significantly degrades users’ experience. In this work, a 3D network structure that undergoes disruption and reorganization with the particles’ movement is utilized in the electrophoretic ink dispersion. Dynamic viscosity modulation enables the bistable and fast-response dual-working modes. The newly developed design can increase the response speed of EPDs by a factor of 2.38, simultaneously maintaining the bistability. The electronic ink with this reversible network provides a promising solution for the future video-rate e-paper displays.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Jinfeng He,Shuqian Yu,Ziyi Ma,Haotian Sun,Qinghua Yang,Zhiwei Liu,Xuan Wang,Xiaoyu Zhang,Longgang Wang
Gold nanoparticles are a kind of good photothermal agents. However, gold nanoparticle photothermal agents have low photothermal conversion efficiency and low tumor inhibiting ability. To overcome these problems, polymyxin E (PE) biomineralized and doxorubicin-loaded gold nanoflowers (DOX-SH@AuNFs) nanodrug was synthesized by the green synthesis method using the biological antimicrobial peptide PE as a stabilizer and grower of crystal seed, and doxorubicin-thiol (DOX-SH) was further loaded on the gold nanoparticles through the Au-S bond. The final DOX-SH@AuNFs displayed a wide absorption band in the UV–Vis spectra, and their photothermal conversion efficiency was 33.9%. Furthermore, the inhibition rate of DOX-SH@AuNFs on A549 cells was as high as 80.1% under the irradiation of near-infrared light at 808 nm. The tumor inhibition rate of DOX-SH@AuNFs was as high as 87.81% in vivo experiments. The high tumor suppression rate was attributed to the high photothermal conversion ability of DOX-SH@AuNFs and the delivery of doxorubicin. Taken together, the method of preparing DOX-SH@AuNFs provides a new idea for the treatment of cancer by photothermal therapy and chemotherapy synergistic system.
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ACS Applied Materials & Interfaces
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2021
·
IF 9.229
Hui Zhi,Xiaobo Zhang,Fengya Wang,Peng Wan,Liang Feng
Flexible pressure sensors made of carbon materials have been used in electronic skins (e-skins), whose performance can be enhanced if composite sensing materials are used. Herein, an MXene/polyaniline/bacterial cellulose (MXene/PANI/BC) aerogel sensor has been fabricated through the self-assembly process between the MXene and one-dimensional active material. Combined with fewer-layer or single-layer MXenes, the as-fabricated aerogel could be used as the active layer of the pressure sensor, monitoring tiny motion signals of finger bending, wrist bending, and pulse beating. Bluetooth wireless transmission could also be realized to monitor the real-time spatial pressure distributions on the mobile phone, making the aerogel-based sensor an ideal candidate in e-skins. Meanwhile, the aerogel-based sensor is sensitive toward NH3 due to the unique three-dimensional (3D) structure of the aerogel and the abundant terminal groups (such as −O, −OH, and −F) of the MXene in the system that ensure efficient electronic transfer for the sensing process and create active sites for the absorption with the target gas. This work offers a versatile platform to develop MXenes to fabricate 3D composite aerogels for high-performance flexible multiple sensors.
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CERAMICS INTERNATIONAL
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2021
·
IF 4.527
Zhiqian Yu,Zhihong Liu,Fengchun Ye,Longgong Xia
Pyrometallurgical processes have been widely recognised as the preferred technology for E-scrap recycling, and E-scrap smelting is usually accompanied by the formation of high-Al 2 O 3 -content slag. However, this slag can cause problems, such as refractory wear and even accelerated failure. Therefore, the corrosion mechanism of magnesia-chrome and alumina-chrome refractories in contact with FeO x -SiO 2 -CaO-Al 2 O 3 smelting slag was experimentally studied in the range of 1300–1400 °C, in air ( p O2 = 0.21 atm) and at p O2 = 10 -7 atm. The results showed that refractory-component dissolution and new phases formation were the major causes of refractory degradation. The dissolution of the refractory components increased along with both increasing temperature and decreasing Al 2 O 3 concentration in the initial slag. When decreasing the p O2 , the dissolution of MgO and Al 2 O 3 into the slag slowed down. New phases such as forsterite, anorthite, and spinel were detected at the interface between the slag and the bulk refractory. The formation of forsterite accelerated the refractory wear, whereas the newly formed (MgO,FeO)·(Cr 2 O 3 ,Fe 2 O 3 ,Al 2 O 3 ) spinel phase acted as a protective layer against further corrosion. A lower Al 2 O 3 concentration in the slag and a higher smelting temperature both densified the formed spinel layer. Additionally, a high oxygen partial pressure was beneficial to the formation of spinel in the magnesia-chrome refractory corrosion experiments. However, a low oxygen partial pressure was favourable for the formation of spinel on the surface of the alumina-chrome refractory materials . This study provides useful information for designing refractory materials and optimizing the processing parameters of E-scrap smelting.
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JOURNAL OF BIOLOGICAL CHEMISTRY
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2021
·Vol. 298
·期 2
·
IF 5.157
Binxiang Cai,Chunyan Liao,Danxue He,Jingmeng Chen,Jiahuai Han,Jiaying Lu,Kaiqi Qin,Wenxu Liang,Xiaoling Wu,Zuguo Liu,Yalin Wu
The breakdown of all-trans-retinal (atRAL) clearance is closely associated with photoreceptor cell death in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its mechanisms remain elusive. Here, we demonstrate that activation of gasdermin E (GSDME) but not gasdermin D promotes atRAL-induced photoreceptor damage by activating pyroptosis and aggravating apoptosis through a mitochondria-mediated caspase-3-dependent signaling pathway. Activation of c-Jun N-terminal kinase was identified as one of the major causes of mitochondrial membrane rupture in atRAL-loaded photoreceptor cells, resulting in the release of cytochrome c from mitochondria to the cytosol, where it stimulated caspase-3 activation required for cleavage of GSDME. Aggregation of the N-terminal fragment of GSDME in the mitochondria revealed that GSDME was likely to penetrate mitochondrial membranes in photoreceptor cells after atRAL exposure. ABC (subfamily A, member 4) and all-trans-retinol dehydrogenase 8 are two key proteins responsible for clearing atRAL in the retina. Abca4−/−Rdh8−/− mice exhibit serious defects in atRAL clearance upon light exposure and serve as an acute model for dry AMD and STGD1. We found that N-terminal fragment of GSDME was distinctly localized in the photoreceptor outer nuclear layer of light-exposed Abca4−/−Rdh8−/− mice. Of note, degeneration and caspase-3 activation in photoreceptors were significantly alleviated in Abca4−/−Rdh8−/−Gsdme−/− mice after exposure to light. The results of this study indicate that GSDME is a common causative factor of photoreceptor pyroptosis and apoptosis arising from atRAL overload, suggesting that repressing GSDME may represent a potential treatment of photoreceptor atrophy in dry AMD and STGD1.
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高影响因子
CHEMISTRY & BIODIVERSITY
·
2021
·Vol. 18
·期 7
·e2100235
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IF 2.408
Zhongtian Fan,Wengui Duan,Guishan Lin,Ming Chen,Mei Huang
In search of novel natural product-based bioactive molecules, twenty (ten pairs) novel ( Z )-/( E )-anisaldehyde-based oxime ester compounds were designed and synthesized by using anisaldehyde as starting material. Structural characterization of the target compounds was carried out by NMR, FT-IR, ESI-MS, and elemental analysis. Their herbicidal and antifungal activities were preliminarily tested. As a result, at 50 μg/mL, compound ( E )- 5b exhibited excellent to good inhibition rates of 92.3 %, 79.2 %, and 73.9 %, against Rhizoctonia solani , Fusarium oxysporum f. sp. cucumerinum , and Bipolaris maydis , respectively, better than or comparable to that of the positive control chlorothalonil. In addition, at 100 μg/mL, compounds ( E )- 5b , ( E )- 5f , ( Z )- 5f and ( E )- 5d exhibited excellent to good inhibition rates of 85.8 %, 82.9 %, 78.6 % and 64.2 %, respectively, against the root-growth of rape ( B. campestris ), much better than that of the positive control flumioxazin. The bioassay result also showed that the synthesized compounds had obvious differences in antifungal and herbicidal activities between ( Z )- and ( E )-isomers. Preliminary structure–activity relationship was also discussed by theoretical calculation. Graphical
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CHEMOSPHERE
·
2020
·
IF 5.778
Yuqiang Xiang,Huaduo Yan,Bingjie Zheng,Aroosha Faheem,Wenli Chen,Yonggang Hu
E. coli @UiO-67 composites were obtained using an effective and simple self-assembly method. The composites showed unique properties as a remarkable and recyclable adsorbent for the efficient removal of bisphenol A (BPA) from water with a high adsorption capacity (402.930 mg g −1 ). The increase in pore size is a key factor why E. coli @UiO-67 composites maintained high capacity. The reason might be due to that the composites with large pore sizes and defects could effectively improve mass transport and active molecular metal sites. The adsorption of BPA is a chemisorption process due to the Zr–OH groups in UiO-67 exhibit affinity toward BPA molecules, π–π interaction, and electrostatic attraction. The adsorption efficiency remained at 82.5% after 15 cycles without any remarkable changes in the PXRD patterns of E. coli @UiO-67. Moreover, the use of microorganism-loading MOFs could reduce the cost to at least 50% and minimize secondary pollution through nanoscale MOFs usage reduction. The developed composites have advantages, including low-cost, high adsorption capacity, easy to be separated and regenerated from aqueous solution, a large number of cycles, short adsorption equilibrium time, and stability, showing excellent application prospects. The presented strategy would be a potentially promising way to produce novel MOFs-based adsorbents with high-performance to control environmental pollution from wastewater.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Longbing Ling,Muhammad Ismail,Zhihao Shang,Yihui Hu,Benhong Li
Irinotecan (Ir) is a potent antitumor chemotherapeutics in clinic and used for the treatment of a various cancers, but the degree of its application is critically limited by toxic side-effects and marked heterogeneities. Nano-formulation of prodrugs, based on “all-in-one” carrier-free self-assemblies offers an effective approach to alter pharmacokinetics and safety profiles of cytotoxic agents. In this study, a novel vitamin E succinate-based formulation of Ir (VES-Ir) combined with nanoscaled characteristics and synergistic combination was constructed through esterification. The conjugation makes amphiphilic VES-Ir prodrug self-assemble into nanoparticles with a fine diameter (VES-Ir NPs, 75.4 nm) of spherical morphology. Furthermore, VES-Ir NPs with a 1:1 drug-to-drug ratio was demonstrated to possess respectable physiological stability within 72 h test, while can react to pH/esterase-sensitive drug release in lysosomes internalized into tumor cells, potentially highlighting their alleviating side effects. Compared with single and mixture drugs administration, the nanoformulated VES-Ir NPs codelivered both VES and Ir with different anticancer mechanisms to induce the highest suppress proliferation of MCF-7 (IC 50 0.18 μM) and A549 (IC 50 0.29 μM) cells in a synergistic way (CI < 1). More importantly, the formulating nanoparticulate Ir is to significantly enhance its bioavailability in vivo with long retention time in bloodstream and thereby, resulting the superior tumor inhibitory rate (TIR) of 85.2% versus controls. This simple nanoformulation of Ir drug deprived from VES conjugation, together with self-delivery and synergistic property, may provide an effective strategy for multiple chemotherapeutics delivery to treat cancers or other diseases.
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Analytical Methods
·
2019
·Vol. 12
·期 2
·193-199
·
IF 2.378
Yan-Jun Huang,Qi-Xin Deng,Hong-Qiao Lan,Zheng-Zhong Fang,Hui Chen,Yan Lin,Han-Chun Xu,Tony D. James,Wei Xie
Nicotine exists in e-liquids primarily as the monoprotonated form and free-base form, the former is absorbed by the smoker relatively slowly and the latter is considered the bioavailable form of nicotine. Nowadays e-liquid manufacturers tend to increase nicotine in smoke aerosols, up to a content comparable to conventional cigarettes. Organic acids are added to suppress nicotine in free-base from, because the quick absorption of free-base nicotine (FBN) by the upper respiratory tract produces more bitterness and harshness to smokers. Although several methods have been developed to access FBN in conventional cigarettes or electronic cigarettes, spectrometric methods have rarely been reported. A water-solubility indicator Alizarin Red S (ARS) was introduced for the measurement of free-base nicotine. Since ARS exhibits lower acidity than organic acids, it does not compete for the tertiary amine with organic acids, but can only interact with FBN. The ARS turns from pale yellow to pink once it has been deprotonated by nicotine, and the binding constant between ARS and nicotine was determined to be 1.08 × 106 M−1. A linear calibration curve A = 0.0056c + 0.3309 with r2 = 0.9984 as a function of FBN was constructed, and applied for the evaluation of FBN in prepared e-liquid samples, with RMSE 1.12 mg g−1 for the 20 mg g−1 liquids, and 1.37 mg g−1 for the 50 mg g−1 liquids. The evaluation of FBN in commercial e-liquids agreed well with published e-liquid values. It is believed that the convenient method herein developed will be useful for manufacturers to balance the strength and harshness levels of nicotine in e-liquids.
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危险品化学品经营许可证（带存储）