| 1. |
- Yen, Ying-Tzu, et al.
(författare)
-
Prominent Enhancement of Cisplatin Efficacy with Optimized Methoxy Poly(ethylene glycol)-Polycaprolactone Block Copolymeric Nanoparticles
- 2020
-
Ingår i: Journal of Biomedical Nanotechnology. - : AMER SCIENTIFIC PUBLISHERS. - 1550-7033 .- 1550-7041. ; 16:3, s. 335-343
-
Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum(II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDP-loaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HO-PCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.
|
|
| 2. |
- Abidine, Yara, et al.
(författare)
-
Cellular Chondroitin Sulfate and the Mucin-like Domain of Viral Glycoprotein C Promote Diffusion of Herpes Simplex Virus 1 While Heparan Sulfate Restricts Mobility
- 2022
-
Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:8
-
Tidskriftsartikel (refereegranskat)abstract
- The diffusion of viruses at the cell membrane is essential to reach a suitable entry site and initiate subsequent internalization. Although many viruses take advantage of glycosaminoglycans (GAG) to bind to the cell surface, little is known about the dynamics of the virus-GAG interactions. Here, single-particle tracking of the initial interaction of individual herpes simplex virus 1 (HSV-1) virions reveals a heterogeneous diffusive behavior, regulated by cell-surface GAGs with two main diffusion types: confined and normal free. This study reports that different GAGs can have competing influences in mediating diffusion on the cells used here: chondroitin sulfate (CS) enhances free diffusion but hinders virus attachment to cell surfaces, while heparan sulfate (HS) promotes virus confinement and increases entry efficiency. In addition, the role that the viral mucin-like domains (MLD) of the HSV-1 glycoprotein C plays in facilitating the diffusion of the virus and accelerating virus penetration into cells is demonstrated. Together, our results shed new light on the mechanisms of GAG-regulated virus diffusion at the cell surface for optimal internalization. These findings may be extendable to other GAG-binding viruses.
|
|
| 3. |
- Hao, Zhengming, et al.
(författare)
-
Converting n-Alkanol to Conjugated Polyenal on Cu(110) Surface at Mild Temperature
- 2022
-
Ingår i: The Journal of Physical Chemistry Letters. - : AMER CHEMICAL SOC. - 1948-7185. ; 13:14, s. 3276-3282
-
Tidskriftsartikel (refereegranskat)abstract
- Achieving C(sp(3))-H activation at a mild temperature is of great importance from both scientific and technologic points of view. Herein, on the basis of the on-surface synthesis strategy, we report the significant reduction of the C(sp(3))-H activation barrier, which results in the full C(sp(3))-H to C(sp(2))-H transformation of n-alkanol (octacosan-1-ol) at a mild temperature as low as 350 K on the Cu(110) surface, yielding the conjugated polyenal (octacosa-tridecaenal) as the final product. The reaction mechanism is revealed by the combined scanning tunneling microscope, density functional theory, and synchrotron radiation photoemission spectroscopy.
|
|
| 4. |
- Hao, Zhengming, et al.
(författare)
-
From n-alkane to polyacetylene on Cu (110): Linkage modulation in chain growth
- 2022
-
Ingår i: Science in China Series B. - : SCIENCE PRESS. - 1674-7291 .- 1869-1870. ; 65:4, s. 733-739
-
Tidskriftsartikel (refereegranskat)abstract
- Direct coupling or transformation of inert alkanes based on the selective C-H activation is of great importance for both chemistry and chemical engineering. Here, we report the coupling of polyenes that are transformed from n-dotriacontane (n-C32H66) through on-surface cascade dehydrogenation on Cu (110) surface, leading to the formation of polyacetylene (PA). Three distinct linkages have been resolved by scanning tunneling microscope (STM) and noncontact atomic force microscope (nc-AFM). Apart from the alpha-type linkage which is the stemless coupling of the terminal C-C double bond in trans-configuration, beta- and gamma-type linkages appear as knots or defects which are, in fact, the C-C couplings in cis-configurations. Interestingly, the "defects" can be effectively suppressed by adjusting the surface coverage, thus making it of general interest for uniform structure modulation.
|
|
| 5. |
- Li, Xuechao, et al.
(författare)
-
Direct transformation of n-alkane into all-trans conjugated polyene via cascade dehydrogenation
- 2021
-
Ingår i: National Science Review. - : Oxford University Press. - 2095-5138 .- 2053-714X. ; 8:10
-
Tidskriftsartikel (refereegranskat)abstract
- Selective C(sp(3))-H activation is of fundamental importance in processing alkane feedstocks to produce high-value-added chemical products. By virtue of an on-surface synthesis strategy, we report selective cascade dehydrogenation of n-alkane molecules under surface constraints, which yields monodispersed all-trans conjugated polyenes with unprecedented length controllability. We are also able to demonstrate the generality of this concept for alkyl-substituted molecules with programmable lengths and diverse functionalities, and more importantly its promising potential in molecular wiring.
|
|
| 6. |
- Liu, Lifeng
(författare)
-
Exploration of host cells during old world alphavirus infection : modulation of RNA granules and the PI3K/AKT pathway
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As obligate intracellular parasites, viruses have to explore and modulate cellular pathways for their survival. Mechanistic studies of virus–host interactions provide a better understanding of viral infection and cellular responses and help to identify potential targets for therapeutic intervention. Alphaviruses, a group of small enveloped viruses with positive-sense, single-stranded RNA genomes, are transmitted by mosquitoes and pose threats to human health. Semliki Forest virus (SFV) belongs to this group and has been extensively studied as a model virus for alphaviruses. Infection with alphaviruses, such as the important human pathogens chikungunya virus (CHIKV) or Ross River virus (RRV), is characterized by high fever, rash and debilitating joint pain, which can last for months or even years. The recent outbreaks and expanding spread of CHIKV in many tropical regions of the world as well as the continuous endemic of RRV in Australasia highlighted the significance of alphavirus research. Stress granules (SGs) are cytoplasmic aggregates of non-translated messenger ribonucleoprotein particles (mRNPs) that can be induced by many types of environmental stress, including viral infection. RNA processing bodies (P-bodies) are cytoplasmic aggregates of translationally silent mRNA and proteins involved in mRNA decay and translation repression. Unlike SGs, P-bodies are constitutively present in the cytoplasm under normal conditions. Both granules can actively respond to environmental stress and associate with each other under certain conditions. The PI3K–Akt–mTOR pathway plays important roles in regulating the transition between cell anabolism and catabolism, responding to changes in the cellular environment. Proper responses of SGs, P-bodies or the PI3K–Akt–mTOR pathway are seen as important adaption for cell survival under stress conditions. In this thesis, it was investigated how alphaviruses (more specifically, Old World alphaviruses such as SFV, CHIKV and RRV) exploit the SG nucleating protein G3BP, P-bodies and the PI3K–Akt–mTOR pathway upon infection. Previous studies have demonstrated that the alphavirus non-structural protein nsP3 binds to the SG nucleating protein G3BP via its two FGDF motifs to block SG induction. In paper I, we compared the two FGDF motifs in nsP3 with respect to their contribution to G3BP binding. The three-dimensional structure of G3BP1 bound to an SFV nsP3-derived peptide (nsP3-25, containing two FGDF motifs) revealed a poly-assembly of G3BP1 dimers inter-connected by nsP3-25. Both in vitro and in vivo binding studies demonstrated a hierarchical binding mode of the duplicate FGDF motifs to G3BP. SFV mutants lacking either of the FGDF motifs failed to bind levels of G3BP necessary for efficient replication, clearly demonstrating that both intact FGDF motifs are required for efficient virus replication. The hierarchical binding mode of two FGDF motifs was also observed for CHIKV nsP3. Growth curves showed that the two intact FGDF motifs are critical for viral replication. Mutation of both FGDF motifs was lethal to CHIKV. These results highlight a conserved molecular mechanism of virus-induced G3BP modulation. In paper II, we described that P-bodies are disassembled or reduced in number after infection with SFV or CHIKV in various cell lines. Disassembly of P-bodies occurs at an early stage (3–4h) post infection and is independent of viral structural protein expression. Similar to SGs, P-bodies could not be re-introduced by a second stress (sodium arsenite) in infected cells. However, formation of SGs or communication between P-bodies and SGs is not necessary for P-body disassembly, since P-bodies were still disassembled to a similar extent upon infection of cells incapable of forming SGs. Studies of the translation status by ribopuromycylation showed that P-body disassembly is independent of host translation shutoff, which requires the phosphorylation of the eukaryotic initiation factor eIF2a in cells infected with SFV or CHIKV. By labelling newly synthesized RNA with bromo-UTP, we observed that the timing of host transcription shutoff correlated with P-body disassembly, occurring at the same stage (3–4h) after infection. However, inhibition of transcription with actinomycin D (ActD) failed to disassemble P-bodies as efficiently as the viruses did. Interestingly, the block of nuclear import in non-infected cells with importazole led to an efficient P-body loss. These results reveal that P-bodies are disassembled independently of SG formation at early stages of Old World alphavirus infection and that nuclear import is involved in the dynamics of P-bodies. Infection with SFV hyperactivates the PI3K–Akt–mTOR pathway. In paper III, we show that a tyrosine residue in the sequence context YEPM in nsP3 of SFV is pivotal for this phenotype. When cells were infected with SFV carrying mutations that affect this motif, such as the replacement of the YEPM tyrosine by phenylalanine (SFV-YF), Akt activation was significantly reduced and delayed in comparison to wildtype SFV infection. Ectopically expressed nsP3 of SFV-WT but not SFV-YF activated the pathway, but only when provided with a membrane anchor. Co-immunoprecipitation experiments revealed that nsP3 of SFV-WT, but not SFV-YF, bound to the regulatory subunit p85 of PI3K, dependent on both the tyrosine of nsP3 and the SH2 domains of p85, which specifically interact with phosphorylated tyrosines in YXXM motifs. This indicates tyrosine phosphorylation of SFV nsP3. A similar YETM motif was identified and characterized in RRV nsP3. Similar to SFV, RRV-WT hyperactivated the PI3K–Akt–mTOR pathway while the mutant RRV-YF, in which the YXXM tyrosine in nsP3 was replaced by phenylalanine, failed to do so.. Complementary experiments showed that infection of cells with SFV or RRV reprograms cellular metabolism and that mutation of the critical tyrosine residue attenuates the virus in cell culture and, in case of RRV, also in mice. These results reveal that the hyperactivation of the PI3K–Akt–mTOR pathway by SFV and RRV, mediated by the interaction of nsP3 and p85, contributes to virus pathogenicity. Taken together, the data from papers I, II and III highlight and characterize three mechanisms by which Old World alphaviruses subvert cells – interactions with the SG nucleating protein G3BP, P-bodies and the PI3K–Akt–mTOR pathway, respectively. These viral subversion mechanisms are largely independent of each other and represent three different modes by which Old World alphaviruses ensure efficient virus growth.
|
|
| 7. |
|
|
| 8. |
- Nan, Pan, et al.
(författare)
-
Design of the laser gun bullets based on microcontroller
- 2018
-
Ingår i: ICEMI 2017 - Proceedings of IEEE 13th International Conference on Electronic Measurement and Instruments. - : Institute of Electrical and Electronics Engineers Inc.. - 9781509050345 ; , s. 68-72
-
Konferensbidrag (refereegranskat)abstract
- Police lab for testing requirements bullet speed, we designed a microcontroller based on the laser gun. The microcontroller as the core for speedometer, with laser detection plate module, thermal Printer module, display and buttons module, USB data interface module, wireless modules and stable voltage module, it can measure the speed of a series of work by Ligation of these modules. First, fired projectiles for testing by the laser detection plate module. Then, Transfer the detected data into the microcontroller. In the microcontroller detection data is processed and then printed out by thermal printer. Via USB data interface for data uploaded to a computer to save. While on the steps required to be operated by the controller. © 2017 IEEE.
|
|
| 9. |
- Song, Luying, et al.
(författare)
-
Synthesis of Two-Dimensional Metal-Organic Frameworks via Dehydrogenation Reactions on a Cu(111) Surface
- 2020
-
Ingår i: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 124:23, s. 12390-12396
-
Tidskriftsartikel (refereegranskat)abstract
- Metal-organic frameworks prepared on surfaces (SMOFs) have been considered to have potential applications in various research fields. Traditionally, the SMOFs are prepared by coadsorbing organic ligands and metal atoms on surfaces. In this article, we successfully construct the SMOFs via the dehydrogenation reactions of aromatic amines on the Cu(111) surfaces. The dehydrogenated nitrogen radicals interact with the copper adatoms, forming the N-Cu-N bonds. Combining with the scanning tunneling microscopy and the density functional theory calculations, we obtain the structural models of the SMOFs.
|
|
| 10. |
- Sultana, M. Afifa, et al.
(författare)
-
Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii Infection
- 2017
-
Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 85:10
-
Tidskriftsartikel (refereegranskat)abstract
- The obligate intracellular parasite Toxoplasma gondii can actively infect any nucleated cell type, including cells from the immune system. The rapid transfer of T. gondii from infected dendritic cells to effector natural killer (NK) cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection. However, subversion of NK cell functions, such as cytotoxicity or production of proinflammatory cytokines, such as gamma interferon (IFN-γ), upon parasite infection might also be beneficial to the parasite. In the present study, we investigated the effects of T. gondii infection on NK cells. In vitro, infected NK cells were found to be poor at killing target cells and had reduced levels of IFN-γ production. This could be attributed in part to the inability of infected cells to form conjugates with their target cells. However, even upon NK1.1 cross-linking of NK cells, the infected NK cells also exhibited poor degranulation and IFN-γ production. Similarly, NK cells infected in vivo were also poor at killing target cells and producing IFN-γ. Increased levels of transforming growth factor β production, as well as increased levels of expression of SHP-1 in the cytosol of infected NK cells upon infection, were observed in infected NK cells. However, the phosphorylation of STAT4 was not altered in infected NK cells, suggesting that transcriptional regulation mediates the reduced IFN-γ production, which was confirmed by quantitative PCR. These data suggest that infection of NK cells by T. gondii impairs NK cell recognition of target cells and cytokine release, two mechanisms that independently could enhance T. gondii survival.
|
|
| 11. |
- Wrande, Marie, et al.
(författare)
-
Replication of Salmonella enterica serovar Typhimurium in RAW264.7 Phagocytes Correlates With Hypoxia and Lack of iNOS Expression
- 2020
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Salmonella infection associates with tissue hypoxia, while inducible nitric oxide synthase (iNOS), relying for its activity on molecular oxygen, stands as a central host defence measure in murine salmonellosis. Here, we have detailed hypoxia and iNOS responses of murine macrophage-like RAW264.7 cells upon infection with Salmonella enterica serovar Typhimurium. We noted that only a proportion of the infected RAW264.7 cells became hypoxic or expressed iNOS. Heavily infected cells became hypoxic, while in parallel such cells tended not to express iNOS. While a proportion of the infected RAW264.7 cells revealed shutdown of protein synthesis, this was only detectable after 12 h post infection and after iNOS expression was induced in the cell culture. Our data implicate an intrinsic heterogeneity with regard to hypoxia and iNOS expression in a cell culture-based infection setting.
|
|
| 12. |
- Zhou, Shuai, et al.
(författare)
-
The calculation of InGaN quantum dot formation mechanism on GaN pyramid
- 2015
-
Ingår i: Superlattices and Microstructures. - : Elsevier. - 0749-6036 .- 1096-3677. ; 84, s. 72-79
-
Tidskriftsartikel (refereegranskat)abstract
- An equilibrium approach is used to calculate the free energy and composition distribution of InGaN/GaN quantum dot located on the InGaN/GaN pyramid. The energy balance method is adopted to predict critical conditions for quantum dot formation. We find that the formation of QD depends strongly on the size of pyramid top surface. The results can fit our experiment qualitatively.
|
|
