| 1. |
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| 2. |
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- 2019
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Journal article (peer-reviewed)
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| 3. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Gao, Zhihui, et al.
(author)
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Mitochondria chaperone GRP75 moonlighting as a cell cycle controller to derail endocytosis provides an opportunity for nanomicrosphere intracellular delivery
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:35, s. 58536-58552
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Journal article (peer-reviewed)abstract
- Understanding how cancer cells regulate endocytosis during the cell cycle could lead us to capitalize this event pharmacologically. Although certain endocytosis pathways are attenuated during mitosis, the endocytosis shift and regulation during the cell cycle have not been well clarified. The conventional concept of glucose-regulated proteins (GRPs) as protein folding chaperones was updated by discoveries that translocated GRPs assume moonlighting functions that modify the immune response, regulate viral release, and control intracellular trafficking. In this study, GRP75, a mitochondria matrix chaperone, was discovered to be highly expressed in mitotic cancer cells. Using synchronized cell models and the GRP75 gene knockdown and ectopic overexpression strategy, we showed that: (1) clathrin-mediated endocytosis (CME) was inhibited whereas clathrinindependent endocytosis (CIE) was unchanged or even up-regulated in the cell cycle M-phase; (2) GRP75 inhibited CME but promoted CIE in the M-phase, which is largely due to its high expression in cancer cell mitochondria; (3) GRP75 targeting by its small molecular inhibitor MKT-077 enhanced cell cycle G1 phase-privileged CME, which provides an opportunity for intracellular delivery of nanomicrospheres sized from 40 nm to 100 nm. Together, our results revealed that GRP75 moonlights as a cell cycle controller and endocytosis regulator in cancer cells, and thus has potential as a novel interference target for nanoparticle drugs delivery into dormant cancer cells.
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| 5. |
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| 6. |
- Yuan, Jun, et al.
(author)
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Understanding energetic disorder in electron-deficient-core-based non-fullerene solar cells
- 2020
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In: Science in China Series B. - : SCIENCE PRESS. - 1674-7291 .- 1869-1870. ; 63:8, s. 1159-1168
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Journal article (peer-reviewed)abstract
- Recent advances in material design for organic solar cells (OSCs) are primarily focused on developing near-infrared non-fullerene acceptors, typically A-DA D-A type acceptors (where A abbreviates an electron-withdrawing moiety and D, an electron-donor moiety), to achieve high external quantum efficiency while maintaining low voltage loss. However, the charge transport is still constrained by unfavorable molecular conformations, resulting in high energetic disorder and limiting the device performance. Here, a facile design strategy is reported by introducing the "wing" (alkyl chains) at the terminal of the DA D central core of the A-DA D-A type acceptor to achieve a favorable and ordered molecular orientation and therefore facilitate charge carrier transport. Benefitting from the reduced disorder, the electron mobilities could be significantly enhanced for the "wing"-containing molecules. By carefully changing the length of alkyl chains, the mobility of acceptor has been tuned to match with that of donor, leading to a minimized charge imbalance factor and a high fill factor (FF). We further provide useful design strategies for highly efficient OSCs with high FF.
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| 7. |
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| 8. |
- Chai, Gaoda, et al.
(author)
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Deciphering the Role of Chalcogen-Containing Heterocycles in Nonfullerene Acceptors for Organic Solar Cells
- 2020
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In: ACS Energy Letters. - : AMER CHEMICAL SOC. - 2380-8195. ; 5:11, s. 3415-3425
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Journal article (peer-reviewed)abstract
- The field of organic solar cells has experienced paradigm-shifting changes in recent years because of the emergence of nonfullerene acceptors (NFAs). It is critically important to gain more insight into the structure-property relationship of the emerging A-DAD-A-type NFAs. In this Letter, a family of NFAs named BPF-4F, BPT-4F, and BPS-4F incorporating various chalcogen-containing heterocycles, i.e., furan, thiophene, and selenophene, respectively, was designed and synthesized. These NFAs exhibited dramatic differences in their photovoltaic performances with device efficiencies of 16.8% achieved by the thiophene-based cells, which was much higher than the furan-based ones (12.6%). In addition, the selenophene-based NFA showed a red-shifted absorption relative to the furan- and thiophene-based ones and obtained a decent efficiency of 16.3% owing to an improved J(SC). The reasons why these NFAs performed differently are systematically studied by comparing their optoelectronic properties and film morphology, which provides new understandings of the molecular design of high-performance NFAs.
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| 9. |
- Chen, Hang, et al.
(author)
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GRP75 upregulates clathrin-independent endocytosis through actin cytoskeleton reorganization mediated by the concurrent activation of Cdc42 and RhoA
- 2016
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In: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 343:2, s. 223-236
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Journal article (peer-reviewed)abstract
- Therapeutic macromolecules are internalized into the cell by either clathrin-mediated endocytosis (CME) or clathrin-independent endocytosis (CIE). Although some chaperone proteins play an essential role in CME (e.g. Hsc70 in clathrin uncoating), relatively few of these proteins are functionally involved in CIE. We previously revealed a role for the mitochondrial chaperone protein GRP75 in heparan sulfate proteoglycan (HSPG)-mediated, membrane raft-associated macromolecule endocytosis. However, the mechanism underlying this process remains unclear. In this study, using a mitochondrial signal peptide-directed protein trafficking expression strategy, we demonstrate that wild-type GRP75 expression enhanced the uptakes of HSPG and CIE marker cholera toxin B subunit but impaired the uptake of CME marker transferrin. The endocytosis regulation function of GRP75 is largely mediated by its subcellular location in mitochondria and is essentially determined by its ATPase domain. Interestingly, the mitochondrial expression of GRP75 or its ATPase domain significantly stimulates increases in both RhoA and Cdc42 activation, remarkably induces stress fibers and enhances filopodia formation, which collectively results in the promotion of CIE, but the inhibition of CME. Furthermore, silencing of Cdc42 or RhoA impaired the ability of GRP75 overexpression to increase CIE. Therefore, these results suggest that endocytosis vesicle enrichment of GRP75 by mitochondria trafficking upregulates CIE through an actin cytoskeleton reorganization mechanism mediated by the concurrent activation of Cdc42 and RhoA. This finding provides novel insight into organelle-derived chaperone signaling and the regulation of different endocytosis pathways in cells.
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| 10. |
- Chong, Hui, et al.
(author)
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Organo-ptii complexes for potent photodynamic inactivation of multi-drug resistant bacteria and the influence of configuration
- 2024
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In: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 11:14
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Journal article (peer-reviewed)abstract
- PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded PtII PSs. The cis-isomer (cis-BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm−2) and 100 nM (18 J cm−2), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm−2) and 1.50 µM (18 J cm−2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.
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| 11. |
- Han, Jing, et al.
(author)
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Identification of N-glycoproteins of knee cartilage from adult osteoarthritis and Kashin-Beck disease based on quantitative glycoproteomics, compared with normal control cartilage
- 2022
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In: Cells. - : MDPI. - 2073-4409. ; 11:16, s. 2513-2513
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Journal article (peer-reviewed)abstract
- Glycoproteins are involved in the development of many diseases, while the type and content of N-glycoproteins in the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) are still unclear. This research aims to identify N-glycoproteins in knee cartilage patients with OA and KBD compared with normal control (N) adults. The cartilage samples were collected from gender- and age-matched OA (n = 9), KBD (n = 9) patients, and N (n = 9) adults. Glycoproteomics and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) obtained N-glycoproteins of KBD and OA. A total of 594 N-glycoproteins and 1146 N-glycosylation peptides were identified. The identified data were further compared and analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interactions (PPI). Pairwise comparison of the glycoproteins detected in the three groups showed that integrin beta-1 (ITGB1), collagen alpha-1 (II) chain (COL2A1), collagen alpha-1 (VII) chain (COL7A1), carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 4 (CHST-4), thrombospondin 2 (THBS2), bone morphogenetic protein 8A (BMP8A), tenascin-C (TNC), lysosome-associated membrane protein (LAMP2), and beta-glucuronidase (GUSB) were significantly differentially expressed. GO results suggested N-glycoproteins mainly belonged to protein metabolic process, single-multicellular and multicellular organism process, cell adhesion, biological adhesion, and multicellular organism development. KEGG and PPI results revealed that key N-glycoproteins were closely related to pathways for OA and KBD, such as phagosome, ECM-receptor interaction, lysosome, focal adhesion, protein digestion, and absorption. These results reflected glycoprotein expression for OA and KBD in the process of ECM degradation, material transport, cell-cell or cell-ECM interaction, and information transduction. These key significantly differentially expressed N-glycoproteins and pathways lead to the degeneration and degradation of the cartilage of OA and KBD mainly by disrupting the synthesis and catabolism of basic components of ECM and chondrocytes and interfering with the transfer of material or information. The key N-glycoproteins or pathways in this research are potential targets for pathological mechanisms and therapies of OA and KBD.
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| 12. |
- Jiang, Tao, et al.
(author)
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Tetraphenylethene end-capped diketopyrrolopyrrole fluorogens with AIE and large two-photon absorption cross-sections features and application in bioimaging
- 2016
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In: Dyes and pigments. - : Elsevier. - 0143-7208 .- 1873-3743. ; 133, s. 201-213
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Journal article (peer-reviewed)abstract
- In this work, a series of new diketopyrrolopyrrole-based dyes have been synthesized by connecting tetraphenylethene to the diketopyrrolopyrrole core. All the four compounds exhibit good aggregation induced emission property with nonemissive in the solution but strong red fluorescence in the aggregate or solid state. Also, these new dyes exhibit large two-photon absorption cross sections (a), in which the a data measured by the open aperture Z-scan technique are determined to be 150, 300, 1140 and 1016 GM for four dyes, respectively. In addition, compound with stilbene and four tetraphenylethene units (DPP-TPE-3) was used as the luminogen and encapsulated into nanoparticles for cell imaging and two-photon excited fluorescence blood vessels imaging. The result indicates that it can be used as the effective fluorescence probe for bioimaging and has great potential for bioapplications. (C) 2016 Elsevier Ltd. All rights reserved.
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| 13. |
- Larsson, David, et al.
(author)
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Patient-specific flow simulation of the left ventricle from 4D echocardiography - feasibility and robustness evaluation
- 2015
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In: 2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS). - : IEEE. - 9781479981823
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Conference paper (peer-reviewed)abstract
- In recent years, computational fluid dynamics (CFD) simulations on in-silico models of the heart have provided a valuable insight into cardiac hemodynamic behaviour. However, so far most models have been either based on simplified geometries or on imaging acquisitions with relatively low temporal resolution. It has been suggested that models based entirely on subject-specific ultrasonic images should be used to capture transient flow changes. Therefore, the aim of this study is to present a pathway from routine 4D echocardiography to a patient-specific flow simulation of the left ventricle (LV), evaluating the model robustness and clinical feasibility. The created pathway consisted of initial LV segmentation and mitral/aortic valve positioning, being subsequently used as input for the CFD simulations (based on solving the Navier-Stokes equation using an Arbitrary Lagrangian-Eulerian approach). The output consisted of 4D blood flow velocities and relative pressures in the entire LV. On five subjects, the model robustness was evaluated with regards to variations in singular boundary conditions. The clinical feasibility of the output was compared to clinical PW Doppler measurements and, as a proof-of-concept, synthetic contrast enhanced ultrasound images were simulated on the flow field using the COLE-method. Results indicated a relatively robust model, with variations in regional flow of approximately 5.1/6.2% and 9.7/7.0% for healthy and pathological subject respectively (end diastole/end systole). Furthermore, showing similar behaviour to clinical Doppler measurements the technique serves as a promising tool for future clinical investigations. Additionally, the ability of simulating synthetic ultrasound images further underlines the applicability of the pathway, being potentially useful in studies on improved echocardiographic image analysis.
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| 14. |
- Lei, Jian, et al.
(author)
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Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis
- 2020
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10
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Journal article (peer-reviewed)abstract
- The pathological mechanism of Kashin-Beck disease (KBD), an endemic osteoarthritic disease, remains to be poorly understood. This study was designed to identify signaling pathways and crucial proteins involved in the pathological mechanism of KBD compared with osteoarthritis (OA). The knee cartilage samples were collected from gender- and age-matched KBD (n = 9) and OA (n = 9) patients. After pre-processing, samples were labeled with Tamdem Mass Tags 6plex multiplex kit, and analyzed by liquid chromatography-tandem mass spectrometry. Proteomic results were analyzed with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI). The differential abundance proteins from KBD and OA were validated using western blot analysis. As a result, A total number of 375 proteins were identified to have differential abundance between KBD and OA, of which 121 and 254 proteins were observed to be up-regulated or down-regulated in KBD group. GO analysis shows that the differential abundant proteins are associated with cell junction and signal transducer activity from extracellular to intracellular. KEGG pathways enrichment and PPI network indicate four major pathways, including extracellular matrix -receptor interaction, focal adhesion, phosphatidylinositol 3-kinase (PI3K)-Protein kinase B (Akt), and Ras signaling pathways were involved in the degeneration of cartilage. Moreover, integrins, laminins, NF-κB and other regulative molecules were found as crucial proteins. In conclusion, our results demonstrated that compared with OA, the differential abundance proteins and signaling pathways may contribute to the occurrence and development of joint damage in KBD. Further investigation of their regulative roles and interaction may provide new insights into the pathological mechanisms and therapeutic targets for KBD.
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| 15. |
- Liu, Junwei, et al.
(author)
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Polymer synergy for efficient hole transport in solar cells and photodetectors
- 2023
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In: Energy & Environmental Science. - : ROYAL SOC CHEMISTRY. - 1754-5692 .- 1754-5706.
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Journal article (peer-reviewed)abstract
- Hole transport materials (HTMs) have greatly advanced the progress of solution-based electronic devices in the past few years. Nevertheless, most devices employing dopant-free organic HTMs can only deliver inferior performance. In this work, we introduced a novel "polymer synergy" strategy to develop versatile dopant-free polymer HTMs for quantum dot/perovskite solar cells and photodetectors. With this synergy strategy, the optical, electrical and aggregation properties of polymer HTMs can be modulated, resulting in complementary absorption, high hole mobility, favorable energy landscape and moderate aggregation. Moreover, a clear orientational transition was observed for the developed HTMs with a 9-fold increase in the face-on/edge-on ratio, providing a highway-like carrier transport for electronic devices, as revealed by in situ characterization and ultrafast transient absorption. With these benefits, the photovoltaic and photodetection performance of quantum dot devices were boosted from 11.8% to 13.5% and from 2.95 x 10(12) to 3.41 x 10(13) Jones (over a 10-fold increase), respectively. Furthermore, the developed polymer HTMs can also significantly enhance the photovoltaic and photodetection performance of perovskite devices from 15.1% to 22.7% and from 2.7 x 10(12) to 2.17 x 10(13)Jones with the same device structure, indicating their great application potential in the emerging optoelectronics.
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| 16. |
- Qiu, Bo, et al.
(author)
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Enhanced gut microbiota delivery of a model probiotic (Faecalibacterium prausnitzii) : Layer-by-layer encapsulation using riboflavin-conjugated sodium alginate and glycol chitosan
- 2024
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In: Food Hydrocolloids. - : Elsevier. - 0268-005X .- 1873-7137. ; 154
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Journal article (peer-reviewed)abstract
- Faecalibacterium prausnitzii (F. prausnitzii) exhibits a variety of biological functions that make it suitable for use as a next-generation probiotic. However, its high sensitivity to oxygen and digestive fluids currently limits its application. Riboflavin is known to support the growth of F. prausnitzii in oxygen environments, but it is important that it is in close proximity to the probiotics. Layer-by-layer assembly can be used to form protective coatings around probiotics, which can protect them from adverse environmental conditions. Moreover, riboflavin can be conjugated to these coatings, thereby increasing its efficacy by bringing it close to probiotic surfaces. In this study, we therefore evaluated the potential of electrostatic layer-by-layer assembly to protect F. prausnitzii by coating them with riboflavin-alginate and glycol-chitosan layers. Initially, we showed that riboflavin could be successfully conjugated to alginate, with a grafting ratio of around 4.35%. Then, the layer-by-layer method was used to coat F. prausnitzii using cationic glycol chitosan and anionic riboflavin-alginate. The coating formed was found to have a thickness of approximately 18.5 nm. Encapsulation did not adversely affect the growth of F. prausnitzii, but it significantly enhanced its resistance to oxygen and digestive fluids. The encapsulated probiotic was shown to have enhanced mucoadhesive properties using an in vitro intestinal monolayer model. Furthermore, the encapsulated probiotics colonized the colons of rats for longer than nonencapsulated ones. These results show that coating F. prausnitzii with riboflavin-rich biopolymer layers improves its resistance to oxygen and digestive fluids, and enhances its mucoadhesion and colonization properties, which should enhance its potential as an orally administered probiotic.
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| 17. |
- Tian, Shangjie, et al.
(author)
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Magnetic topological insulator MnBi6 Te10 with a zero-field ferromagnetic state and gapped Dirac surface states
- 2020
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In: Physical Review B. - 2469-9950. ; 102:3
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Journal article (peer-reviewed)abstract
- Magnetic topological insulators (TIs) with nontrivial topological electronic structure and broken time-reversal symmetry exhibit various exotic topological quantum phenomena. The realization of such exotic phenomena at high temperature is one of the central topics in this area. We reveal that MnBi6Te10 is a magnetic TI with an antiferromagnetic ground state below 10.8 K whose nontrivial topology is manifested by Dirac-like surface states. The ferromagnetic axion insulator state with Z4=2 emerges once spins are polarized at a field as low as 0.1 T, accompanied with saturated anomalous Hall resistivity up to 10 K. Such a ferromagnetic state is preserved even with an external field down to zero at 2 K. Theoretical calculations indicate that the few-layer ferromagnetic MnBi6Te10 is also topologically nontrivial with a nonzero Chern number. Angle-resolved photoemission spectroscopy experiments further reveal three types of Dirac surface states arising from different terminations on the cleavage surfaces, one of which has insulating behavior with an energy gap of ∼28 meV at the Dirac point. These outstanding features suggest that MnBi6Te10 is a promising system to realize various topological quantum effects at zero field and high temperature.
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| 18. |
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| 19. |
- Zhang, Chujun, et al.
(author)
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A disorder-free conformation boosts phonon and charge transfer in an electron-deficient-core-based non-fullerene acceptor
- 2020
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In: Journal of Materials Chemistry A. - : ROYAL SOC CHEMISTRY. - 2050-7488 .- 2050-7496. ; 8:17, s. 8566-8574
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Journal article (peer-reviewed)abstract
- Electron acceptors with a chemical structure of A-DA D-A (in which A denotes an acceptor moiety and D a donor moiety) are rapidly gaining prominence in organic solar cells (OSCs). In OSCs containing these acceptors, record power conversion efficiencies (PCEs) exceeding 16% are now widely reported. Despite encouraging advances related to new material designs and PCEs, the fundamental interplay between molecular structure and device performance still requires further understanding. Here, we choose two model A-DA D-A type acceptors, Y3 and Y18, that have almost identical structures, and examine how the presence of two extra alkyl chains (attached to the periphery of the DA D core) in Y18 impacts on its solid state properties and device performance. These properties include: (i) charge transport; (ii) heat transfer; and (iii) electronic disorder. We found that bulk-heterojunction (BHJ) OSCs that use Y3 and Y18 have markedly different PCEs of similar to 13 and 16%, respectively. Correspondingly, the BHJ containing Y18 possesses more efficient phonon transfer and charge transport and suppressed electronic disorder. Among these properties, the extremely low Urbach energy (E-U) of 23 meV in Y18 stands out because this is even below the thermal energy (similar to 26 meV), which sets the electronic disorder limit at room temperature. With all these contrasting results, a simple molecular model can be rationalized in which the extra alkyl chains in Y18 help to suppress the formation of rotamers, endowing it with a disorder free molecular conformation and remarkable solid state properties. This work provides not only a new physical understanding of the effect of alkyl chains in organic semiconductors, but also new ideas for the synthesis of novel materials that can be adopted for use in high-performance OSCs.
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| 20. |
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