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1.
Org Biomol Chem ; 22(29): 5999-6003, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38993018

RESUMO

An unusual spiroannulation/cycloisomerization cascade of 3-(2-ethynylaryl)-N-tosylaziridines with indoles enabled by cooperative gold/scandium catalysis is presented, which facilitates the synthesis of 5H-benzo[b]carbazoles in moderate to excellent yields. This protocol features a broad substrate scope and good functional-group compatibility. Additionally, the resulting 5H-benzo[b]carbazoles exhibit good fluorescence properties, demonstrating the synthetic practicality of this method. Moreover, control experiments were performed to illustrate the reaction mechanism.

2.
Curr Opin Cell Biol ; 88: 102377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823338

RESUMO

Nonvesicular lipid transport among different membranes or membrane domains plays crucial roles in lipid homeostasis and organelle biogenesis. However, the forces that drive such lipid transport are not well understood. We propose that lipids tend to flow towards the membrane area with a higher membrane protein density in a process termed lipid osmosis. This process lowers the membrane tension in the area, resulting in a membrane tension difference called osmotic membrane tension. We examine the thermodynamic basis and experimental evidence of lipid osmosis and osmotic membrane tension. We predict that lipid osmosis can drive bulk lipid flows between different membrane regions through lipid transfer proteins, scramblases, or similar barriers that selectively pass lipids but not membrane proteins. We also speculate on the biological functions of lipid osmosis. Finally, we explore other driving forces for lipid transfer and describe potential methods and systems to further test our theory.


Assuntos
Osmose , Animais , Humanos , Membrana Celular/metabolismo , Membrana Celular/química , Metabolismo dos Lipídeos , Transporte Biológico , Lipídeos/química
3.
bioRxiv ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38260424

RESUMO

Nonvesicular lipid transport among different membranes or membrane domains plays crucial roles in lipid homeostasis and organelle biogenesis. However, the forces that drive such lipid transport are not well understood. We propose that lipids tend to flow towards the membrane area with a higher membrane protein density in a process termed lipid osmosis. This process lowers the membrane tension in the area, resulting in a membrane tension difference called osmotic membrane tension. We examine the thermodynamic basis and experimental evidence of lipid osmosis and osmotic membrane tension. We predict that lipid osmosis can drive bulk lipid flows between different membrane regions through lipid transfer proteins, scramblases, or other similar barriers that selectively pass lipids but not membrane proteins. We also speculate on the biological functions of lipid osmosis. Finally, we explore other driving forces for lipid transfer and describe potential methods and systems to further test our theory.

4.
bioRxiv ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38895381

RESUMO

Cellular mechanotransduction, a process central to cell biology, embryogenesis, adult physiology and multiple diseases, is thought to be mediated by force-driven changes in protein conformation that control protein function. However, methods to study proteins under defined mechanical loads on a biochemical scale are lacking. We report the development of a DNA based device in which the transition between single-stranded and double-stranded DNA applies tension to an attached protein. Using a fragment of the talin rod domain as a test case, negative-stain electron microscopy reveals programmable extension while pull down assays show tension-induced binding to two ligands, ARPC5L and vinculin, known to bind to cryptic sites inside the talin structure. These results demonstrate the utility of the DNA clamp for biochemical studies and potential structural analysis.

5.
Int J Biol Macromol ; 277(Pt 4): 134513, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111468

RESUMO

The early diagnosis and real-time monitoring of bacterial infections are of great significance for the establishment of integrated diagnosis and treatment systems. In this study, a pH-responsive smart hydrogel patch system, named CABP, was developed to monitor and treat wound infections. CABP has a sandwich structure, with non-woven fabric/chitosan (NF/CS) as the intermediate skeleton layer, Agarose/chitosan/Bromothymol Blue (AG/CS/BTB) hydrogel as the detection layer, and Agarose/chitosan/phthalocyanine (AG/CS/Pc) hydrogel as the treatment layer. When Staphylococcus aureus (S. aureus) infection occurs, the pH of the environment decreases, which triggers the CABP to change from its original blue color to yellow, achieving an intuitive visual transformation. Moreover, the hydrogel patch showed a significant inhibition rate of up to 99.99971 % against S. aureus under 660 nm light radiation, showing a good photodynamic therapy (PDT)/ chemotherapy (CT) synergistic effect. In addition, CABP showed excellent antibacterial and wound healing effects on S. aureus infection in a full-layer skin defect experiment. In short, the patch system is simple to prepare and easy to use, and can provide important research value for the integrated diagnosis and treatment system in biomedical applications.

6.
bioRxiv ; 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38766144

RESUMO

Nucleoporins (nups) in the central channel of nuclear pore complexes (NPCs) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptors (NTRs) with bound cargos. The complex molecular interactions between nups and NTRs have been thought to underlie the gatekeeping function of the NPC. Recent studies have shown considerable variation in NPC diameter but how altering NPC diameter might impact the selective barrier properties remains unclear. Here, we build DNA nanopores with programmable diameters and nup arrangement to mimic NPCs of different diameters. We use hepatitis B virus (HBV) capsids as a model for large-size cargos. We find that Nup62 proteins form a dynamic cross-channel meshwork impermeable to HBV capsids when grafted on the interior of 60-nm wide nanopores but not in 79-nm pores, where Nup62 cluster locally. Furthermore, importing substantially changes the dynamics of Nup62 assemblies and facilitates the passage of HBV capsids through NPC mimics containing Nup62 and Nup153. Our study shows the transport channel width is critical to the permeability of nup barriers and underscores the role of NTRs in dynamically remodeling nup assemblies and mediating the nuclear entry of viruses.

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