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1.
Biomaterials ; 293: 121982, 2023 02.
Article in English | MEDLINE | ID: mdl-36640555

ABSTRACT

Human pluripotent stem cell-derived hepatocytes (hPSC-Heps) may be suitable for treating liver diseases, but differentiation protocols often fail to yield adult-like cells. We hypothesised that replicating healthy liver niche biochemical and biophysical cues would produce hepatocytes with desired metabolic functionality. Using 2D synthetic hydrogels which independently control mechanical properties and biochemical cues, we found that culturing hPSC-Heps on surfaces matching the stiffness of fibrotic liver tissue upregulated expression of genes for RGD-binding integrins, and increased expression of YAP/TAZ and their transcriptional targets. Alternatively, culture on soft, healthy liver-like substrates drove increases in cytochrome p450 activity and ureagenesis. Knockdown of ITGB1 or reducing RGD-motif-containing peptide concentration in stiff hydrogels reduced YAP activity and improved metabolic functionality; however, on soft substrates, reducing RGD concentration had the opposite effect. Furthermore, targeting YAP activity with verteporfin or forskolin increased cytochrome p450 activity, with forskolin dramatically enhancing urea synthesis. hPSC-Heps could also be successfully encapsulated within RGD peptide-containing hydrogels without negatively impacting hepatic functionality, and compared to 2D cultures, 3D cultured hPSC-Heps secreted significantly less fetal liver-associated alpha-fetoprotein, suggesting furthered differentiation. Our platform overcomes technical hurdles in replicating the liver niche, and allowed us to identify a role for YAP/TAZ-mediated mechanosensing in hPSC-Hep differentiation.


Subject(s)
Hepatocytes , Oligopeptides , Humans , Colforsin/metabolism , Colforsin/pharmacology , Cell Differentiation , Oligopeptides/pharmacology , Oligopeptides/metabolism , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P-450 Enzyme System/pharmacology , Hydrogels/chemistry
2.
ACS Appl Mater Interfaces ; 13(14): 16507-16515, 2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33784811

ABSTRACT

The adsorption process is widely used for the treatment of wastewater containing organic pollutants. We fabricated highly branched pillar[5]arene-based porous aromatic frameworks (PAFs), PAF-P5, for the adsorption and removal of organic pollutants (short-chain alkyl derivatives 1-3 and pesticide molecules 4-6) from water with high removal efficiency (RE). However, PAF-P5 was incapable of adsorbing aromatic organic dyes 7-9. Adsorption kinetic studies indicated that the adsorption is mainly driven by strong host-guest interactions between 1-3 and the pillar[5]arene units in PAF-P5, while 4-6 only weakly interacted with the pillar[5]arene units in PAF-P5. Moreover, chemically breaking down the pillar[5]arene rings in PAF-P5 caused changes in the pore size, the microenvironment inside of the pores, and the frame morphology, and the resultant frameworks, PAF-DeP5, exhibited poor adsorption toward 1-6 but adsorbed 7-9 possibly through physical adsorption as implied by fitting the experimental data into the adsorption kinetic models.

3.
Chemistry ; 26(10): 2269-2275, 2020 Feb 17.
Article in English | MEDLINE | ID: mdl-31845388

ABSTRACT

Graphyne, a theorized carbon allotrope possessing only sp- and sp2 -hybridized carbon atoms, holds great potentials in many fields, especially in catalysis and energy-transfer/storage devices. Using a bottom-up strategy, we synthesized a new N-doped graphyne analogue, triazine- and 1,4-diethynylbenzene-based graphyne TA-BGY, in solution in gram-scale. The unique sp/sp2 carbon-conjugated TA-BGY possesses an extended porous network structure with a BET surface area of approximately 300 m2 g-1 . Owing to its low optical band gap (1.44 eV), TA-BGY was expected to have many applications, which were exemplified by the photodegradation of methyl orange and photocatalytic bacterial inactivation.


Subject(s)
Coloring Agents/chemistry , Graphite/chemistry , Triazines/chemistry , Azo Compounds/chemistry , Catalysis , Escherichia coli/drug effects , Graphite/chemical synthesis , Graphite/pharmacology , Light , Photolysis/radiation effects , Porosity , Quantum Theory
4.
Org Biomol Chem ; 17(18): 4600-4604, 2019 05 08.
Article in English | MEDLINE | ID: mdl-31016307

ABSTRACT

Synthetic investigation of the systematic replacement of alkoxy groups in pillar[5]arene by cyano ones was carried out. 2nCN-pillar[5]arenes (n = 1, 2, 3, 4 or 5) bearing different numbers of cyano functions on their rims were successfully prepared for the first time. Single-crystal X-ray diffraction studies showed that the nCN-pillar[5]arenes had unique conformations in the solid states. Besides, host-guest property studies of those nCN-pillar[5]arenes and 1,4-dicyanobutane showed the functionization number-related host-guest interaction varieties.

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