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Controllable regulations on the enzyme conformation to optimize catalytic performance are highly desired for the immobilized biocatalysts yet remain challenging. Covalent organic frameworks (COFs) possess confined channels with finely tunable pore environment, offering a promising platform for enzyme encapsulation. Herein, we covalently immobilized the cytochrome c (Cyt c) in the size‐matched channels of COFs with different contents of anchoring site, and significant enhancement of the stability and activity (≈600 % relative activity compared with free enzyme) can be realized by optimizing the covalent interactions. Structural analyses on the immobilized Cyt c suggest that covalent bonding could induce conformational perturbation resulting in more accessible active sites. The effectiveness of the covalent interaction modulation together with the tailorable confined channels of COFs offers promise to develop high‐performance biocatalysts.

Aim Given the fact that tumor-associated macrophage-derived extracellular vesicles (EVs) are attributable to tumor aggressiveness, this research intends to decode the mechanism of M2 macrophage-derived EVs in the differentiation and activities of pancreatic cancer (PaCa) stem cells via delivering microRNA (miR)-21-5p. Methods Polarized M2 macrophages were induced, from which EVs were collected and identified. miR-21-5p expression in M2 macrophage-derived EVs was tested. After cell sorting, CD24+CD44+EpCAM+ stem cells were co-cultured with M2 macrophages, in which miR-21-5p was upregulated or downregulated. The effects of M2 macrophage-derived EVs and miR-21-5p on Nanog/octamer-binding transcription factor 4 (Oct4) expression, sphere formation, colony formation, invasion and migration capacities, apoptosis, and in vivo tumorigenic ability were examined. Krüppel-like factor 3 (KLF3) expression and its interaction with miR-21-5p were determined. Results M2 macrophage-derived EVs promoted PaCa stem cell differentiation and activities. miR-21a-5p was upregulated in M2 macrophage-derived EVs. miR-21a-5p downregulation in M2 macrophage-derived EVs inhibited Nanog/Oct4 expression and impaired sphere-forming, colony-forming, invasion, migration, and anti-apoptosis abilities of PaCa stem cells in vitro and tumorigenic ability in vivo. miR-21-5p targeted KLF3 to mediate the differentiation and activities of PaCa stem cells, and KLF3 was downregulated in PaCa stem cells. Conclusion This work explains that M2 macrophage-derived exosomal miR-21a-5p stimulates differentiation and activity of PaCa stem cells via targeting KLF3, paving a novel way for attenuating PaCa stemness. Graphical abstract

Controllable regulations on the enzyme conformation to optimize catalytic performance are highly desired for the immobilized biocatalysts yet remain challenging. Covalent organic frameworks (COFs) possess confined channels with finely tunable pore environment, offering a promising platform for enzyme encapsulation. Herein, we covalently immobilized the cytochrome c (Cyt c) in the size‐matched channels of COFs with different contents of anchoring site, and significant enhancement of the stability and activity (≈600 % relative activity compared with free enzyme) can be realized by optimizing the covalent interactions. Structural analyses on the immobilized Cyt c suggest that covalent bonding could induce conformational perturbation resulting in more accessible active sites. The effectiveness of the covalent interaction modulation together with the tailorable confined channels of COFs offers promise to develop high‐performance biocatalysts.

Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) are representative crystalline porous polymers. Due to their high surface area, high porosity, open channels, abundant functional groups and easy functionalization, they show great applications in gas storage and separation, catalysis, energy storage, photovoltaic devices, etc. Amino acids are the basic structural units that constitute peptides and proteins, which not only have important biological functions, but also play an important role in industrial applications such as pharmaceutical production, biodegradable plastics, and chiral catalysts. The introduction of amino acids into MOFs and COFs could endow them with diverse and flexible frameworks, special pore environment, and chiral sites, improving their biocompatibility and degradability to some extent and enriching their functions and applications. This review focuses on the progress of the amino acid functionalized MOFs and COFs, including their synthetic strategies, such as employing amino acids and their derivatives as building unit, covalent modification of amino acids onto the framework, and utilizing amino acids as modulators. The advantages and disadvantages of these strategies are compared and their challenges are discussed. In addition, we also introduce their applications in chiral separation, catalysis, adsorption and proton conduction. Finally, we summarize the current challenges in the preparation of amino acid functionalized crystalline porous polymers and outlook the future research direction in this field. Keywords crystalline porous polymer; metal-organic frameworks; covalent organic frameworks; amino acid; functionalization 1 引言 晶态多孔聚合物是一类具有丰富结构和官能团、高 结晶度、 高比表面积、 发达孔道结构的功能多孔材料, 展 现出良好的应用前景, 近年来该领域取得了长足的发 展 [1]. 其中, 金属有机框架(metal-organic frameworks, MOFs)或称多孔配位聚合物(porous coordination polymers, PCPs), 是由金属离子/团簇和有机配体组装形成 的无机有机杂化多孔材料 [2] ; 共价有机框架(covalent organic frameworks, COFs)是由有机构筑单元通过共价 键组装而成的晶态多孔材料 [3]. 与传统的多孔材料相比, 晶态多孔聚合物具有以下特点: (1)丰富可设计的组成和 结构, 在网状化学的设计理念下可通过调控构筑单元及 其连接方式构筑具有不同结构特征的框架结构; (2)规整 有序的孔道结构, 且可对其孔径、形状、化学环境进行 调控; (3)易于官能化, 可通过官能化的构筑单元或合成 后修饰的策略实现骨架的功能化 [1a]. 因此, 此类材料在