MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Ningze Zheng,Shurui Liu,Jianheng Chen,Yue Xu,Wenyin Cao,Jinyi Lin,Guang Lu,Guigen Zhang
The development of biomolecule delivery systems is essential for the treatment of various diseases such as cancer, immunological diseases, and metabolic disorders. For the first time, we found that SARS-CoV-2-encoded nonstructural protein 2 (NSP2) can be secreted from the cells, where it is synthesized. Brefeldin A and H89, inhibitors of ER/Golgi secretion pathways, did not inhibit NSP2 secretion. NSP2 is likely secreted via an unconventional secretory pathway. Moreover, both secreted and purified NSP2 proteins were able to traverse the plasma membrane barrier and enter both immortalized human umbilical vein endothelial cells and tumor cell lines. After entry, the NSP2 protein was localized in only the cytoplasm. Cytochalasin D, a potent inhibitor of actin polymerization, inhibited the entry of NSP2. NSP2 can carry other molecules into cells. Burkholderia lethal factor 1, a monomeric toxin from the intracellular pathogen Burkholderia pseudomallei, has demonstrated antitumor activity by targeting host eukaryotic initiation translation factor 4A. An NSP2-BLF1 fusion protein was translocated across the cellular membranes of Huh7 cells and mediated cell killing. By using different approaches, including protein purification, chemical inhibition, and cell imaging, we confirm that NSP2 is able to deliver heterologous proteins into cells. NSP2 can act as a potential delivery vehicle for proteins.
研究领域:
分子生物学
·
细胞生物学
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癌症研究
·
药理学
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DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Mengchen Li,Bo Li,Binbin Long,Leibin Li,Yang Chen,Mingye Peng,Mengzhou Zhou
Lactobacillus plantarum R is the predominant bacterium widely used in food fermentation. However, it has a low tolerance to ethanol during fermentation, which restricts its broader application in the food industry. Although biofilm formation enhances bacterial resistance to various stresses, regulating biofilm formation in L. plantarum R remains challenging. In this study, we established a pathway for producing autoinducer 2 (AI-2), a quorum-sensing (QS) signaling molecule, by heterologously expressing pfs and LuxS in L. plantarum R. This approach aimed to modulate cell membrane structure and improve bacterial ethanol resistance. The findings showed that exogenous AI-2 significantly enhanced the growth of L. plantarum R under high-ethanol concentration and improved its biofilm formation at different ethanol concentrations. Furthermore, a multi-omics analysis revealed potential mechanisms by which AI-2 improved the tolerance of L. plantarum R to ethanol. Notably, the upregulation of the crr gene, a component of the phosphotransferase system (PTS), enhanced biofilm formation in response to ethanol stress. In addition, differential metabolites enriched in cysteine and methionine metabolic pathways further supported the role of QS in enhancing the tolerance of L. plantarum R to ethanol. These findings lay the groundwork for enhancing the fermentation performance of strains applied in the food fermentation industry, presenting a novel method for expanding the utilization of L. plantarum R in high-ethanol fermentation.
研究领域:
微生物学
·
食品生物技术
·
分子生物学
·
系统生物学
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合成生物学
·
发酵技术
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产品关联
DOI
高影响因子
FUEL
·
2025
·
IF 7.5
Wanpeng Li,Xuewei Zhang,Guangmai Zhao,Tianhan Zhu,Mi Luo,Tianyu Gao,Chenguang Wang,Xiaoyu Chen,Jin Tan,Yuhe Liao,Haiyong Wang
The efficient and sustainable transformation of biomass-derived furfural into value-added chemicals is a key challenge in green chemistry. In this study, a series of Pt/CeO 2 catalysts with varying Pt loadings (0.1–2.0 wt%) were synthesized via a carbonization–reduction method and applied for the selective conversion of furfural to 2-furfural diethanol in ethanol under mild conditions. Comprehensive characterization using XRD, XPS, EPR, TEM, and Py-FTIR revealed that the 1.0 wt% Pt/CeO 2 catalyst exhibited optimal properties, including high dispersion of metallic Pt⁰, abundant oxygen vacancies, enriched Ce 3+ species, and dominant Lewis acid sites. Catalytic tests demonstrated that under mild conditions (20 °C, 4 MPa N 2 ), the 1.0 wt% Pt/CeO 2 catalyst achieved the highest yield (92.17 %) and furfural conversion (95.41 %). Mechanistic studies suggest a proposed redox-driven tandem hydrogenation–condensation pathway, where the synergistic effect between Pt⁰ sites and oxygen vacancies facilitates furfural activation, hydrogen transfer, and product formation. This work provides a mechanistic understanding of furfural upgrading over Pt/metal oxide interfaces and offers a promising strategy for the rational design of high-performance catalysts for biomass valorization.
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产品关联
DOI
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2016
·Vol. 182
·期 3
·898-909
·
IF 1.606
Xu Jian-Miao,Cheng Feng,Fu Fang-Tian,Hu Hai-Feng,Zheng Yu-Guo
L -2-aminobutyric acid ( L -ABA) as a precursor for the anticonvulsant and the antituberculotic is a key intermediate in the chemical and pharmaceutical industries. Recently, leucine dehydrogenase (LeuDH) with NAD + regeneration was developed for L -ABA production on a large scale. Previously, the L -ABA yield was improved by optimizing conversion conditions, including cofactor regeneration and enzyme immobilization but not protein engineering on LeuDH due to lacking an applicable high-throughput screening (HTS) method. Recently, an HTS assay was developed by us, which enables researchers to engineer LeuDH in a relatively short period of time. Herein, a semirational engineering was performed on LeuDH to increase the catalytic efficiency of BcLeuDH. Firstly, the structure of wild-type (WT) BcLeuDH was modeled and seven potentially beneficial positions were selected for mutation. Five beneficial variants were then identified from the seven site-saturation mutagenesis (SSM) libraries by HTS and confirmed by rescreening via amino acid analyzer. The “best” variant M5 (WT + Q358N) showed 44.5-fold higher catalytic efficiency ( k
cat / K
M ) than BcLeuDH WT, which suggested that BcLeuDH M5 is an attractive candidate for L -ABA production on a large scale. Furthermore, the structure-functional relationship was investigated based on the docking and kinetic results.
研究领域:
生物技术
·
生物化工
·
酶学
·
药学
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DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2020
·
IF 4.303
Xueyin Ru,Ning Tao,Yanyan Feng,Qingqing Li,Qingguo Wang
Enzymatic browning is one of the essential issues affecting the quality of fresh-cut produce. In this study, we identified a novel, safe, and effective anti-browning agent, 3-mercapto-2-butanol, which can prevent fresh-cut potatoes from browning for 5 d under the concentration of 25 μL L −1 at 5 °C. The inhibitory effect of 3-mercapto-2-butanol was close to sodium bisulfite. 3-Mercapto-2-butanol was further identified as a competitive inhibitor which directly inhibited the activity of polyphenol oxidase (PPO) by enzyme kinetic analysis, and the expression levels of PPO-related genes ( POT32 and POT33 ) were decreased after 3-mercapto-2-butanol treatment. Besides, the concentration of enzymatic browning substrate tyrosine (Tyr) in the potato chips was found significantly higher in 3-mercapto-2-butanol treatment group than in the control group. We speculated that 3-mercapto-2-butanol could reduce the consumption of Tyr by inhibiting the activity of PPO. Our finding not only provided a novel and safe anti-browning agent candidate (3-mercapto-2-butanol) to efficiently solve the browning issue for fresh-cut food products, but also preliminarily revealed its mechanism in browning inhibition.
研究领域:
食品科学
·
植物生理学
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DOI
高影响因子
FEMS MICROBIOLOGY LETTERS
·
2015
·Vol. 362
·期 6
·
IF 2.121
Zhao Jianqing,Pan Shan,Lin Lan,Fu Lei,Yang Chao,Xu Zhongmin,Wei YanMin,Jin Meilin,Zhang Anding
Streptococcus suis (S. suis) ranks among the five most important porcine pathogens worldwide and occasionally threatens human health, especially in people that come into close contact with pigs or pork products. Streptococcus suis serotype 2 (SS2) is considered to be the most pathogenic and prevalent capsular type. As a first line of immune defense against SS2 infection, neutrophils can eliminate the invader not only by phagocytosis but also by neutrophil extracellular traps (NETs)-mediated killing. SS2 can resist phagocytosis through polysaccharide capsule (CPS), but how this strain evades the effects of NETs remains to be determined. The present study demonstrated that the epidemic strain 05ZY, the highly pathogenic strain P1/7 and the intermediately pathogenic strain A7 could induce the formation of NETs. Furthermore, SS2 strains could successfully resist NETs-mediated killing, and the CPS structure contributed to this resistance by escaping the trapping. Therefore, the CPS structure not only contributed to the SS2 strains’ resistance to phagocytosis-mediated killing but also played an essential role in evading NETs trapping and further killing in vitro. This study strengthens our understanding of how S. suis can evade innate immune surveillance and elimination.
研究领域:
微生物学
·
免疫学
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DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Yu-Xuan Dai,Wen-Li Xin,Lian-Hua Xu,Ji Li,Yi-Xuan Li,Junji Li,Serge Cosnier,Xue-Ji Zhang,Robert S. Marks,Dan Shan
Rational design highly active transition metal or transition metal oxides/nanocarbon hybrids is one of the feasible way to deliver a cooperative oxygen reduction (ORR) with a synergistic effect of the hybrid interface. Herein, based on benzimidazole-5-carboxylate (BIMC), CoO/Co-N-C nanocomposites are fabricated via 2-methylimidazole (2-MeIm)-tuned “4-Self” strategy, namely, self-templating, self-adapting, self-assembly and self-catalysis. As a base competitive ligand with N and C sources, 2-MeIm modulates the dispersion of BIMC in methanol to generate collodial-like BIMC tiny particles, the coordination ability of BIMC to Co(II), the composition and morphology of the self-assembled precursor (Co-BM), and as well as the conductivity of the resultant electrocatalyst. Impressing, carbonization of Co-BM at 800 °C under N 2 atmosphere endows the pyrolysis product (Co-BM-800) with the well-dispersed Co/CoO riveted on nitrogen-doped carbon, as well as the enhanced ORR performance in terms of positive onset-potential (0.890 V vs. RHE), large diffusion limiting current density (5.21 mA cm −2 ), and high stability.
研究领域:
材料科学
·
电化学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Ruijin Zeng,Minghao Qiu,Qing Wan,Zhisheng Huang,Xiaolong Liu,Dianping Tang,Dietmar Knopp
Large-scale, rapid, and inexpensive serological diagnoses of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) are of great interest in reducing virus transmission at the population level; however, their development is greatly plagued by the lack of available point-of-care methods, leading to low detection efficiency. Herein, an ultrasensitive smartphone-based electrochemical immunoassay is reported for rapid (less than 5 min), low-cost, easy-to-implement detection of the SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 N protein). Specifically, the electrochemical immunoassay was fabricated on a screen-printed carbon electrode coated with electrodeposited gold nanoparticles, followed by incubation of anti-N antibody (Ab) and bovine serum albumin as the working electrode. Accompanied by the antigen–antibody reaction between the SARS-CoV-2 N protein and the Ab, the electron transfer between the electroactive species [Fe(CN)6]3–/4– and the electrode surface is disturbed, resulting in reduced square-wave voltammetry currents at 0.075 V versus the Ag/AgCl reference electrode. The proposed immunoassay provided a good linear range with SARS-CoV-2 N protein concentrations within the scope of 0.01–1000 ng/mL (R2 = 0.9992) and the limit of detection down to 2.6 pg/mL. Moreover, the detection data are wirelessly transmitted to the interface of the smartphone, and the corresponding SARS-CoV-2 N protein concentration value is calculated and displayed. Therefore, the proposed portable detection mode offers great potential for self-differential diagnosis of residents, which will greatly facilitate the effective control and large-scale screening of virus transmission in resource-limited areas.
研究领域:
医学诊断
·
生物传感器
·
病毒学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Yabing Xing,Wentao Hu,Yuxin Li,Yuru Zhang,Yulu Zhang,Binghua Wang,Xinhong Guo
Purpose 2-Methoxyestradiol (2-ME) has been demonstrated to possess extensive antitumor effects; however, various challenges have impeded its clinical utilization. In this study, we aimed to design a novel oral delivery system for 2-ME using a dual-target modification strategy to address the inherent drawbacks associated with poor absorption and rapid elimination, as well as to enhance oral bioavailability and antitumor effects.Methods Mannose(M)-modified zein (MZ) and cysteine(C)-modified zein (CZ) were synthesized. Glucose transporter (GLUT)-targeted adhesive nanoparticles (NPs), designated as 2-ME-CMZ (1:1:9)-NPs, were prepared via a solvent evaporation method using MZ, CZ, and Zein at a mass ratio of 1:1:9. Their in vitro and in vivo properties, including in vitro release, adhesion, antitumor effects etc. were evaluated.Results Compared with 2-ME-NPs, 2-ME-CMZ (1:1:9)-NPs showed a 3.89-fold increase in mucin adsorption in simulated intestinal fluid (SIF), a 0.61-fold extension of mean residence time (MRT), and a 1.2-fold increase in Caco-2 cell uptake, thereby prolonging the maintenance time of effective concentration (MTEC) after single-dose administration by 2.53-fold and enhancing oral bioavailability by 3.7-fold and tumor growth inhibition rate by 1.06-fold. Interestingly, for 2-ME-CMZ (1:1:9)-NPs, their cellular uptake was related to the mediation of multiple subtypes of GLUT with relative specificity, and they significantly enhanced the original cellular uptake pathway of 2-ME-NPs and showed higher tumor distribution than 2-ME-NPs. However, merely modifying 2-ME-NPs with mannose only increased the oral bioavailability of 2-ME-NPs by 0.44-fold.Conclusion Compared with 2-ME-NPs, 2-ME-CMZ (1:1:9)-NPs significantly enhanced absorption through the mediation of multiple subtypes of GLUT, enhancing their original cellular uptake pathway and prolonging absorption time. These findings demonstrated that 2-ME-CMZ (1:1:9)-NPs are an extremely promising oral drug delivery system for 2-ME, and endowing GLUT-targeted drug-loaded nanoparticles with adhesion is an effective strategy for fully leveraging the role of GLUT in mediating oral absorption.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Xufang Huang,Jing Wu,Xiaorui Xing,Yi Wang,Changzheng Wu,Shijie Li,Shuo Wang
Heavy metals and mycotoxins are important contaminants in food pollution. Sensitive, reliable, and rapid detection of heavy metals and mycotoxins is crucial for human health. In this work, imidazole-functionalized aggregation-induced emission (AIE) molecule tetra-(4-pyridylphenyl) ethylene (TPPE) was used as a precise and specific probe for Ag + detection, with a limit of detection (LOD) of 0.0318 μM. Meanwhile, a large amount of hydrophobic TPPE molecules were loaded into the amphiphilic block copolymer F127 to form ultrabright fluorescent microspheres (TPPENPs). Lateral flow immunochromatography (LFIA) based on immunoprobe (TPPENPs-Ab) has been successfully developed. The LOD of TPPENPs-LFIA for T-2 toxin was 0.13 μg/L, which was 13.31-fold and 8.62-fold more sensitive than that of gold nanoparticles-based LFIA and ordinary fluorescent microspheres-based LFIA, respectively. TPPENPs-LFIA was employed to detect T-2 toxin in actual grain samples, with a spiked recovery rate of 71.69 - 111.13 %. This assay offers a promising strategy and new idea for multi-target detection.
研究领域:
食品科学
·
分析化学
·
生物医学
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产品关联
DOI
PubMed
高影响因子
ELECTROCHIMICA ACTA
·
2017
·
IF 4.798
Yaohua Yang,Kai Yan,Jingdong Zhang
A Ni(OH) 2 /TiO 2 photoanode possessing high photoelectrocatalytic activity toward glucose oxidation driven by visible light was fabricated. The results indicated that deposition of Ni(OH) 2 on TiO 2 film electrode could remarkably promote the catalytic oxidation of glucose under visible light illumination. By applying a low voltage, the Ni(OH) 2 /TiO 2 electrode showed a linear photoelectrochemical response to glucose in the concentration range from 0.5 μM to 20 μM. Furthermore, the high photoelectrocatalytic activity of Ni(OH) 2 /TiO 2 electrode toward glucose oxidation was utilized to construct a glucose-air photofuel cell, which generated electrical signal responding to glucose concentration from 5 μM to 100 μM, without using external electrical power supply. Thus, dual non-enzymatic glucose sensors based on photocatalytic oxidation of glucose on the Ni(OH) 2 /TiO 2 electrode under visible light illumination were demonstrated.
研究领域:
生物医学工程
·
材料科学
·
分析化学
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DOI
高影响因子
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
·
2025
·Vol. 41
·期 11
·451
·
IF 4.2
Zhong Chenggang,Ding Weijian,Lin Haoran,Huang Jin
Cellobiose-2-epimerase is considered an ideal biocatalyst for the strictly thermodynamic synthesis of lactulose. However, its poor thermolability limits its industrial application. Herein, we successfully developed a novel thermostable cellobiose-2-epimerase for improving lactulose biosynthesis from lactose. The A242L mutant, derived from Dictyoglomus thermophilum (DiCE), was generated using semi-rational mutagenesis after computer-aided design via the FireProt web server. After systematic enzymatic characterization and optimization, A242L mutant exhibited a 123.5% T 1/2 in thermostability at 80 °C relative to the wild-type enzyme, and the E. coli BL21/pET28a(+)-A242L mutant harvested a maximal lactulose yield of 64.52%, representing a 51.38% improvement at a substrate concentration of 200 g/L for the whole-cell biotransformation reaction conducted at pH 7.0 and 80 °C for 4 h. Molecular docking and molecular dynamics (MD) simulation results indicated that the enhanced thermostability of the enzyme was closely related to the structure and rigidity of its flexible loops. The enhanced thermostability allows A242L to tolerate higher temperatures for extended periods, driving the reaction towards lactulose production, which is suitable for industrial lactulose production under harsh conditions.
研究领域:
酶工程
·
工业生物技术
·
生物化学
·
分子生物学
·
生物催化
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）