Frontiers in Microbiology
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2023
·
IF 5.2
Du Wenlong,Xu Ruolin,He Zhiqiang,Yang Huan,Gu Yufan,Liu Yi
Critically ill patients have higher risk of serious fungal infections, such as invasive aspergillosis (IA) which is mainly caused by the human fungal pathogen Aspergillus fumigatus. Triazole drugs are the primary therapeutic agents for the first-line treatment of IA, which could easily cause drug resistance problems. Here, we assess the potential of AgNPs synthesized with Artemisia argyi leaf extract and domiphen as new antifungal agents to produce synergistic antimicrobial effects on Aspergillus fumigatus, and dissect possible molecular mechanisms of action. Plate inoculation assays combined with drug susceptibility test and cytotoxicity test showed that the combination of AgNPs and domiphen has synergistic antimicrobial effects on A. fumigatus with low cytotoxicity. Gene Ontology (GO) enrichment analysis showed that AgNPs and domiphen inhibit the growth of A. fumigatus by suppressing nitrate assimilation, and purine nucleobase metabolic process and amino acid transmembrane transport, respectively. When the two drugs are combined, AgNPs has epistatic effects on domiphen. Moreover, the combination of AgNPs and domiphen primarily influence secondary metabolites biosynthesis, steroid biosynthesis and nucleotide sugar metabolism of A. fumigatus via Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, protein–protein interactions (PPI) analysis combined with validation experiments showed that the combination of AgNPs and domiphen could enhance the expression of copper transporter and inhibit nitrogen source metabolism. In addition, the synergistic antimicrobial effects could be enhanced or eliminated depending on exogenous addition of copper and nitrogen source, respectively. Taken together, the results of this study provide a theoretical basis and a new strategy for the treatment of IA.
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FOOD CONTROL
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2023
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IF 6
Mengyue Guo,Jing zhang,Jianxin Lv,Tongwei Ke,Jiao Tian,Kun Miao,Yudan Wang,Dandan Kong,Haonan Ruan,Jiaoyang Luo,Meihua Yang
The frequent occurrence of ochratoxins in food and herbs poses a considerable threat to consumer and animal health. Here, we generated a broad-specificity monoclonal antibody against three ochratoxins. Concentrations for 50% inhibition (IC 50 ) for OTA, OTB, and OTC were 0.37, 0.23, and 2.24 ng/mL, respectively. In the two matrices, the proposed indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) exhibited a limit of detection (LOD) of 1.5 μg/kg for OTA and 1.0 μg/kg for OTB, respectively, whereas the cut-off levels of lateral flow immunoassay (LFIA) for OTA and OTB were respectively determined to be 1 and 0.25 ng/mL. As for OTC, the LOD of ic-ELISA and cut-off concentration of LFIA were 15.5 μg/kg and 8 ng/mL for milkvetch root and 37.5 μg/kg and 16 ng/mL for ginger, respectively. The real sample detection results by ic-ELISA and LFIA methods were validated via LC-MS/MS analysis. Therefore, the developed immunoassays are useful and effective tools for high-throughput screening and rapid on-site determination of ochratoxins in complex matrices.
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Foods
·
2023
·Vol. 12
·期 2
·393
·
IF 5.2
Yuanping Zhang,Fenghua Wu,Zhiping He,Xuezhi Fang,Xingquan Liu
In recent years, food-derived hypoglycemic peptides have received a lot of attention in the study of active peptides, but their anti-diabetic mechanism of action is not yet clear. In this study, camellia seed cake protein (CSCP) was used to prepare active peptides with α-glucosidase inhibition. The optimization of the preparation of camellia seed cake protein hydrolyzed peptides (CSCPH) was conducted via response surface methodology (RSM) using a protamex withα-glucosidaseinhibition as an indicator. The optimal hydrolysis conditions were pH 7.11, 4300 U/g enzyme concentration, 50 °C hydrolysis temperature, and 3.95 h hydrolysis time. Under these conditions, theα-glucosidaseinhibition rate of CSCPH was 58.70% (IC508.442 ± 0.33 mg/mL). The peptides with highα-glucosidase inhibitory activitywere isolated from CSCPH by ultrafiltration and Sephadex G25. Leu-Leu-Val-Leu-Tyr-Tyr-Glu-Tyr (LLVLYYEY) and Leu-Leu-Leu-Leu-Pro-Ser-Tyr-Ser-Glu-Phe (LLLLPSYSEF) were identified and synthesized for the first time by Liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) analysis and virtual screening with IC50values of 0.33 and 1.11 mM, respectively. Lineweaver-Burk analysis and molecular docking demonstrated that LLVLYYEY was a non-competitive inhibitor ofα-glucosidase, whereas LLLLPSYSEF inhibitedα-glucosidase, which displayed a mixed inhibition mechanism. The study suggests the possibility of using peptides from Camellia seed cake as hypoglycaemic compounds for the prevention and treatment of diabetes.Keywords:camellia seed cake protein (CSCP);α-glucosidase;Inhibition kinetic;molecular docking
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ANALYTICAL CHEMISTRY
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2023
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IF 7.4
Rongfan Ren,Minghui Yuan,Hongli Li,David Da Yong Chen
Carbohydrates play critically important roles in energy supply and biological functions in living systems. However, it has been a great challenge to identify saccharides and distinguish their isomers because they have highly similar structures and many possible positions for glycosidic linkages. In this work, an ambient ionization tandem mass spectrometry method was developed to characterize disaccharide structural isomers with in situ methylation. The direct analysis in real time ion source can be used to facilitate the methylation reaction of disaccharides with tetramethylammonium hydroxide. The hydroxyl groups of disaccharides can be methylated instantaneously, and the products can be ionized at the same time. The methylated product ions from full scan mass spectrometry (MS) and tandem MS can be used to distinguish a variety of disaccharide structural isomers with different glycosidic linkages, compositions, and configurations. Characteristic marker ions were discovered, and they can be used for the assignment of linkage type and identification of specific isomeric forms. The method was used for the direct identification of disaccharide isomers from real commercial products such as honey, wine, and milk without complex sample pretreatment or chromatographic separation.
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EXPERIMENTAL AND MOLECULAR MEDICINE
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2023
·Vol. 55
·期 1
·183-195
·
IF 12.8
Wu Zhuhua,Zhu Li,Nie Xinran,Wei Li,Qi Yong
Pulmonary hypertension (PH) is a life-threatening cardiopulmonary disease characterized by pulmonary vascular remodeling. Excessive growth and migration of pulmonary artery smooth muscle cells (PASMCs) are believed to be major contributors to pulmonary vascular remodeling. Ubiquitin-specific protease 15 (USP15) is a vital deubiquitinase that has been shown to be critically involved in many pathologies. However, the effect of USP15 on PH has not yet been explored. In this study, the upregulation of USP15 was identified in the lungs of PH patients, mice with SU5416/hypoxia (SuHx)-induced PH and rats with monocrotaline (MCT)-induced PH. Moreover, adeno-associated virus-mediated functional loss of USP15 markedly alleviated PH exacerbation in SuHx-induced mice and MCT-induced rats. In addition, the abnormal upregulation and nuclear translocation of YAP1/TAZ was validated after PH modeling. Human pulmonary artery smooth muscle cells (hPASMCs) were exposed to hypoxia to mimic PH in vitro, and USP15 knockdown significantly inhibited cell proliferation, migration, and YAP1/TAZ signaling in hypoxic hPASMCs. Rescue assays further suggested that USP15 promoted hPASMC proliferation and migration in a YAP1/TAZ-dependent manner. Coimmunoprecipitation assays indicated that USP15 could interact with YAP1, while TAZ bound to USP15 after hypoxia treatment. We further determined that USP15 stabilized YAP1 by inhibiting the K48-linked ubiquitination of YAP1. In summary, our findings reveal the regulatory role of USP15 in PH progression and provide novel insights into the pathogenesis of PH.
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Analytical Methods
·
2023
·Vol. 15
·期 4
·419-429
·
IF 3.1
Yu Fan,Xin Wang,He Huang,Yumeng Yang,Jinlin Guo,Shajie Luo,Meilian Zhao,Yang Li
As the “mother of antioxidants”, glutathione (GSH) plays an important role in physiological functions. Rapid and accurate monitoring of GSH is of great significance for medicinal chemistry, food chemistry, and clinical medicine. We herein report a visual ratiometric fluorescence sensor based on MnO2 nanowires (MnO2 NWs) as an oxidant, quencher and recognition unit for the determination of GSH. The powerful ratiometric fluorescent probe was constructed by mixing thiamine (VB1) and rhodamine B (RhB) with the help of MnO2 NWs. MnO2 NWs could not only effectively quench the fluorescence of RhB due to the inner filter effect (IFE), but also oxidized non-fluorescent VB1 to blue fluorescent thiochrome (oxVB1). Upon interaction with GSH, the quenched RhB fluorescence could be rapidly restored through decomposition of MnO2 NWs into Mn2+, while the oxVB1 fluorescence decreased, showing an apparent color change from blue to red. The concentration of GSH was proportional to the ratio of fluorescence intensities of RhB and oxVB1, and the detection linear range was 1 to 10 000 μM with comparable selectivity. This ratio fluorescence sensor was successfully applied to GSH determination in whitening capsules and glutathione tablets with satisfactory results, and the sensor may be a potentially powerful tool for the detection of GSH.
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ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Duo Chen,Na Chen,Fangning Liu,Yiming Wang,Huageng Liang,Yanbing Yang,Quan Yuan
Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I–III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.
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Nature Communications
·
2022
·Vol. 13
·期 1
·1-15
·
IF 17.694
Liu Tian,Li Lingxiao,Wang Shuo,Dong Fudan,Zuo Shiyi,Song Jiaxuan,Wang Xin,Lu Qi,Wang Helin,Zhang Haotian,Cheng Maosheng,Liu Xiaohong,He Zhonggui,Sun Bingjun,Sun Jin
Sulfur bonds, especially trisulfide bond, have been found to ameliorate the self-assembly stability of homodimeric prodrug nanoassemblies and could trigger the sensitive reduction-responsive release of active drugs. However, the antitumor efficacy of homodimeric prodrug nanoassemblies with single reduction-responsivity may be restricted due to the heterogeneous tumor redox microenvironment. Herein, we replace the middle sulfur atom of trisulfide bond with an oxidizing tellurium atom or selenium atom to construct redox dual-responsive sulfur-tellurium-sulfur and sulfur-selenium-sulfur hybrid chalcogen bonds. The hybrid chalcogen bonds, especially the sulfur-tellurium-sulfur bond, exhibit ultrahigh dual-responsivity to both oxidation and reduction conditions, which could effectively address the heterogeneous tumor microenvironment. Moreover, the hybrid sulfur-tellurium-sulfur bond promotes the self-assembly of homodimeric prodrugs by providing strong intermolecular forces and sufficient steric hindrance. The above advantages of sulfur-tellurium-sulfur bridged homodimeric prodrug nanoassemblies result in the improved antitumor efficacy of docetaxel with satisfactory safety. The exploration of hybrid chalcogen bonds in drug delivery deepened insight into the development of prodrug-based chemotherapy to address tumor redox heterogeneity, thus enriching the design theory of prodrug-based nanomedicines.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
·
IF 6.51
Jiangtao Wu,Xiangbin Du,Dongmei Zhang,Jicheng Cui,Xiaoxia Zhang,Xine Duan,John F. Trant,Yingqi Li
Cancer chemotherapy is often accompanied by severe off-target effects that both damage quality of life and can decrease therapeutic compliance. This could be minimized through selective delivery of cytotoxic agents directly to the cancer cells. This would decrease the drug dose, consequently minimizing side effects and cost. With this goal in mind, a dual-gated folate-functionalized nanodiamond drug delivery system (NPFSSD) for doxorubicin with activatable fluorescence and cytotoxicity has been prepared. Both the cytotoxic activity and the fluorescence of doxorubicin (DOX) are quenched when it is covalently immobilized on the nanodiamond. The NPFSSD is preferentially uptaken by cancer cells overexpressing the folate receptor. Then, once inside a cell, the drug is preferentially released within tumor cells due to their high levels of endogenous of glutathione , required for releasing DOX through cleavage of a disulfide linker. Interestingly, once free DOX is loaded onto the nanodiamond, it can also evade resistance mechanisms that use protein pumps to remove drugs from the cytoplasm. This nanodrug, used in an in vivo model with local injection of drugs, effectively inhibits tumor growth with fewer side effects than direct injection of free DOX, providing a potentially powerful platform to improve therapeutic outcomes.
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MOLECULES
·
2022
·Vol. 27
·期 23
·8200
·
IF 4.927
Qianqian Han,Tongtong Zhang,Meifang Wang,Fei Yan,Jiyang Liu
Rapid and highly sensitive quantitative analysis of chlorpromazine (CPZ) in human whole blood is of great importance for human health. Herein, we utilize the screen-printed carbon electrodes (SPCE) as the electrode substrates for growth of highly electroactive and antifouling nanocomposite materials consisting of vertically ordered mesoporous silica films (VMSF) and electrochemically reduced graphene oxide (ErGO) nanosheets. The preparation of such VMSF/ErGO/SPCE could be performed by using an electrochemical method in a few seconds and the operation is controllable. Inner ErGO layer converted from graphene oxide (GO) in the growth process of VMSF provides oxygen-containing groups and two-dimensional π-conjugated planar structure for stable fabrication of outer VMSF layer. Owing to the π-π enrichment and excellent electrocatalytic abilities of ErGO, electrostatic preconcentration and antifouling capacities of VMSF, and inherent disposable and miniaturized properties of SPCE, the proposed VMSF/ErGO/SPCE sensor could be applied for quantitative determination of CPZ in human whole blood with high accuracy and sensitivity, good stability, and low sample consumption.Keywords:vertically ordered mesoporous silica films;screen-printed carbon electrodes;electrochemically reduced graphene oxide;chlorpromazine;electrochemical sensors;human whole blood
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Foods
·
2022
·Vol. 11
·期 23
·3768
·
IF 5.561
Ziwei Wang,Fujun Liu,Ying Luo,Xiangbo Zeng,Xuechen Pei,Guanhua Zhao,Min Zhang,Dayong Zhou,Fawen Yin
Antarctic krill (Euphausia superba) oil contains high levels of marine omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In industrial production, krill oil is usually extracted from krill meals by using ethanol as a solvent. Water in the krill meal can be easily extracted by using ethanol as an extraction solvent. During the extraction process, the EPA and DHA are more easily oxidized and degraded when water exists in the ethanol extract of krill oil. Based on the analysis of peroxide value (POV), thiobarbituric acid-reactive substances (TBARS), fatty acid composition, and lipid class composition, the present study indicated that the composite antioxidants (TP-TPP) consist of tea polyphenol (TP) and tea polyphenol palmitate (TPP) had an excellent antioxidant effect. By contrast, adding TP-TPP into ethanol solvent during the extraction process is more effective than adding TP-TPP into krill oil after the extraction process.Keywords:antarctic krill;oil;antioxidant;tea polyphenol;composite antioxidants;ethanol
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DIAMOND AND RELATED MATERIALS
·
2022
·
IF 3.806
Zongwei Guo,Zhao Wang,Jiajun Ma,De Sun,Yuhui Ao,Lin Jin
To construct a high-performance fiber-based composite, it is important to ensure a suitable interface existing between fiber and matrix. However, poor interfacial adhesion restrains the performance of carbon fiber composites due to the confined interaction forces between fiber and matrix. Cation-π interactions play an irreplaceable role in the mussel adhesion, offering an alternative strong interaction between substrate and matrix. Hence, inspired by this, on the premise of no damage to fiber's structure, a novel and versatile coating of carbon fiber was obtained by molecule design. The designed cation polymer acting as a strong interfacial linker was coupled with negatively charged carbon fiber via cation-π interactions quickly, resulting in enhanced physical and chemical bonding, which boosts the interfacial adhesion of carbon fiber composites significantly. Benefiting from this coating, the interlaminar shear strength (ILSS) and flexural strength of modified composite were increased by 38.9 % and 83.5 %, respectively. This work provides a new pathway to develop advanced functional coating for fiber-based composites to deal with complex environments.
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