Adipocyte-derived exosomal miR-22-3p modulated by circadian rhythm disruption regulates insulin sensitivity in skeletal muscle cells.

Circadian rhythm disruption leads to dysregulation of lipid metabolism, which further drive the occurrence of insulin resistance (IR). Exosomes are natural carrier systems that advantageous for cell communication. In the present study, we aimed to explore whether and how the exosomal microRNAs (miRNAs) in circulation participate in modulating skeletal muscle IR induced by circadian rhythm disruption. In the present study, 24-h constant light (12-h light/12-h light, LL) was used to establish the mouse model of circadian rhythm disruption. Bmal1 interference was used to establish the cell model of circadian rhythm disruption. And in clinical experiments, we chose a relatively large group of rhythm disturbance-shift nurses. We showed that LL-induced circadian rhythm disruption led to increased body weight and visceral fat volume, as well as occurrence of IR in vivo. Furthermore, exosomal miR-22-3p derived from adipocytes in the context of circadian rhythm disruption induced by Bmal1 interference could be uptaken by skeletal muscle cells to promote IR occurrence in vitro. Moreover, miR-22-3p in circulation was positively correlated with the clinical IR-associated factors. Collectively, these data showed that exosomal miR-22-3p in circulation may act as potential biomarker and therapeutic target for skeletal muscle IR, contributing to the prevention of diabetes in the context of rhythm disturbance.

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1.

BACKGROUND: Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear. METHODS: The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells. RESULTS: POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance. CONCLUSION: Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.

Sub-3 nm Pt@Ru toward Outstanding Hydrogen Oxidation Reaction Performance in Alkaline Media.

Anion-exchange membrane fuel cells (AEMFCs) are promising alternative hydrogen conversion devices. However, the sluggish kinetics of the hydrogen oxidation reaction in alkaline media hinders further development of AEMFCs. As a synthesis method commonly used to prepare disordered PtRu alloys, the impregnation process is ingeniously designed herein to synthesize sub-3 nm Pt@Ru core-shell nanoparticles by sequentially reducing Pt and Ru at different annealing temperatures. This method avoids complex procedures and synthesis conditions for organic synthesis systems, and the atomic structure evolution of the synthesized core-shell nanoparticles can be tracked. The synthesized Pt@Ru electrocatalyst shows an ultrasmall average size of ∼2.5 nm and thereby a large electrochemical surface area (ECSA) of 166.66 m2 gPt+Ru-1. Exchange current densities (j0) normalized to the mass (Pt + Ru) and ECSA of this electrocatalyst are 8.0 and 5.8 times as high as those of commercial Pt/C, respectively. To the best of our knowledge, the achieved mass-normalized j0 measured by rotating disk electrodes is the highest reported so far. The membrane electrode assembly test of the Pt@Ru electrocatalyst shows a peak power density of 1.78 W cm-2 (0.152 mgPt+Ru cmanode-2), which is higher than that of commercial PtRu/C (1.62 W cm-2, 0.211 mgPt+Ru cmanode-2). The improvement of the intrinsic activity can be attributed to the electron transfer from the Ru shell to the Pt core, and the ultrafine particles further enhance the mass activity. This work reveals the feasibility of using simple impregnation to synthesize fine core-shell nanocatalysts and the importance of investigating the atomic structure of PtRu nanoparticles and other disordered alloys.

Identification and protective role of CD34+ stromal cells/telocytes in experimental autoimmune encephalomyelitis (EAE) mouse spleen.

Experimental autoimmune encephalomyelitis (EAE) is a classical animal model of human multiple sclerosis (MS) that is most commonly used to study the neuropathology and therapeutic effects of the disease. Telocytes (TCs) are a specialized type of interstitial or mesenchymal cell first identified by Popescu in various tissues and organs. However, the existence, distribution and role of CD34+ stromal cells (SCs)/TCs in the EAE-induced mouse spleen remain to be elucidated. We conducted immunohistochemistry, immunofluorescence (double staining for CD34 and c-kit, vimentin, F4/80, CD163, Nanog, Sca-1, CD31 or tryptase) and transmission electron microscopy experiments to investigate the existence, distribution and role of CD34+ SCs/TCs in the EAE-induced mouse spleen. Interestingly, immunohistochemistry, double-immunofluorescence, and transmission electron microscopy results revealed that CD34+ SCs/TCs were significantly upregulated in the EAE mouse spleen. Immunohistochemical or double-immunofluorescence staining of CD34+ SCs/TCs showed positive expression for CD34, c-kit, vimentin, CD34/vimentin, c-kit/vimentin and CD34/c-kit, and negative expression for CD31 and tryptase. Transmission electron microscopy (TEM) results demonstrated that CD34+ SCs/TCs established close connections with lymphocytes, reticular cells, macrophages, endothelial cells and erythrocytes. Furthermore, we also found that M1 (F4/80) or M2 (CD163) macrophages, and haematopoietic, pluripotent stem cells were markedly increased in EAE mice. Our results suggest that CD34+ SCs/TCs are abundant and may play a contributing role in modulating the immune response, recruiting macrophages and proliferation of haematopoietic and pluripotent stem cells following injury to promote tissue repair and regeneration in EAE mouse spleens. This suggests that their transplantation combined with stem cells might represent a promising therapeutic target for the treatment and prevention of multiple autoimmune and chronic inflammatory disorders.

An efficient nickel hydrogen oxidation catalyst for hydroxide exchange membrane fuel cells.

The hydroxide exchange membrane fuel cell (HEMFC) is a promising energy conversion technology but is limited by the need for platinum group metal (PGM) electrocatalysts, especially for the hydrogen oxidation reaction (HOR). Here we report a Ni-based HOR catalyst that exhibits an electrochemical surface area-normalized exchange current density of 70 µA cm-2, the highest among PGM-free catalysts. The catalyst comprises Ni nanoparticles embedded in a nitrogen-doped carbon support. According to X-ray and ultraviolet photoelectron spectroscopy as well as H2 chemisorption data, the electronic interaction between the Ni nanoparticles and the support leads to balanced hydrogen and hydroxide binding energies, which are the likely origin of the catalyst's high activity. PGM-free HEMFCs employing this Ni-based HOR catalyst give a peak power density of 488 mW cm-2, up to 6.4 times higher than previous best-performing analogous HEMFCs. This work demonstrates the feasibility of efficient PGM-free HEMFCs.

Functional Regulation and Stability Engineering of Three-Dimensional Covalent Organic Frameworks.

ConspectusAs one of the most attractive members in the porous materials family, covalent organic frameworks (COFs) have been reported thousands of times since their first discovery in 2005, covering their design, synthesis, and applications. However, an overwhelming majority of these COFs are based on two-dimensional (2D) topologies while three-dimensional (3D) COFs are numbered fewer than 100 up to date. In fact, baring enhanced specific surface area, interconnected channels, well-exposed functional moieties, and highly adjustable structures, 3D COFs are often more competitive in various application fields like adsorption, separation, chemical sensing, and heterogeneous catalysis compared with their 2D counterparts. However, significant crystallization problems and poor chemical stabilities, which might be attributed to the highly void frameworks and the absence of π-π stacking, have raised severe limitations over the research and application of 3D COFs. To solve these problems, more elaborate synthesis regulations or more moderate functionalization conditions are required. More importantly, the strategies for enhancing chemical stabilities of 3D COFs are of vital importance for their further development and practical applications.In this Account, we review the design principles, functional approaches, and stability regulation methods toward functional 3D COFs. We begin the discussion with some essential elements in the construction of 3D COF structures, including topologies, interpenetrations, linkages, and synthetic methods. After that, we focus on several strategies for the functionalization of 3D COFs, including in situ approaches (utilizing in situ generated COF linkages as the active sites), bottom-up synthesis (embedding functional moieties from predesigned building blocks), and postsynthesis modification (covalent modification or metalation of pristine frameworks). At last, we highlight some approaches toward the durable amplification of 3D COFs, which is highly important for framework functionalization and practical application. This target could be achieved through not only the introduction of some extra strengthening force, such as hydrophobic effects, coulomb repulsion, and steric hindrance effects, but also the utilization of robust linkages, which could enhance the stability from material nature.Due to their high surface area, various interpenetrated channels, multifarious functionalities, and promising stabilities, 3D COFs demonstrated excellent performance and have great potential in a wide range of application fields including adsorption and separation, heterogeneous catalysis, energy storage, and so on. Although the development of these materials has been limited by serious crystallization problems and stability restriction, great efforts have been devoted by researchers in the past decade, and a mass of strategies have been developed in synthesis control, functionalization regulation, and stability enhancement for 3D COFs. We expect 3D COFs to be practically utilized in the future with further advances in the design, preparation, and functionalization of these materials.

Design and Synthesis of a Zeolitic Organic Framework.

The development of novel zeolite-like materials with large channel windows and high stability is of importance but remains a tremendous challenge. Herein, we report the first example of a 3D covalent organic framework with zeolitic network, namely the zeolitic organic framework (ZOF). By combining two kinds of tetrahedral building blocks with fixed or relatively free bond angles, ZOF-1 with the zeolitic crb net has been successfully synthesized. Its structure was determined by the single-crystal 3D electron diffraction technique. Remarkably, ZOF-1 shows high chemical stability, large pore size (up to 16 Å), and excellent specific surface area (≈2785 m2 g-1 ), which is superior to its analogues with the same network, including traditional aluminosilicate zeolites and zeolitic imidazole frameworks. This study thus opens a new avenue to construct zeolite-like materials with pure organic frameworks and will promote their potential applications in adsorption and catalysis for macromolecules.

Three-Dimensional Triptycene-Functionalized Covalent Organic Frameworks with hea Net for Hydrogen Adsorption.

Owing to the finite building blocks and difficulty in structural identification, it remains a tremendous challenge to elaborately design and synthesize three-dimensional covalent organic frameworks (3D COFs) with predetermined topologies. Herein, we report the first two cases of 3D COFs with the non-interpenetrated hea net, termed JUC-596 and JUC-597, by using the combination of tetrahedral and triangular prism building units. Due to the presence of triptycene functional groups and fluorine atoms, JUC-596 exhibits an exceptional performance in the H2 adsorption up to 305 cm3 g-1 (or 2.72 wt%) at 77 K and 1 bar, which is higher than previous benchmarks from porous organic materials reported so far. Furthermore, the strong interaction between H2 and COF materials is verified through the DFT theoretical calculations. This work represents a captivating example of rational design of functional COFs based on a reticular chemistry guide and demonstrates its promising application in clean energy storage.

Gating Effects for Ion Transport in Three-Dimensional Functionalized Covalent Organic Frameworks.

The development of bioinspired nano/subnano-sized (<2 nm) ion channels is still considered a great challenge due to the difficulty in precisely controlling pore's internal structure and chemistry. Herein, for the first time, we report that three-dimensional functionalized covalent organic frameworks (COFs) can act as an effective nanofluidic platform for intelligent modulation of the ion transport. By strategic attachment of 12-crown-4 groups to the monomers as ion-driver door locks, we demonstrate that gating effects of functionalized COFs can be activated by lithium ions. The obtained materials exhibit an outstanding selective ion transmission performance with a high gating ratio (up to 23.6 for JUC-590), which is among the highest values in metal ion-activated solid-state nanochannels reported so far. Furthermore, JUC-590 offers high tunability, selectivity, and recyclability of ion transport proved by the experimental and simulated studies.

Involvement of miR-27a-3p in diabetic nephropathy via affecting renal fibrosis, mitochondrial dysfunction, and endoplasmic reticulum stress.

Diabetic nephropathy (DN) is acknowledged as a serious chronic complication of diabetes mellitus. Nevertheless, its pathogenesis is complicated and unclear. Thus, in this study, the role of miR-27a-3p-prohibitin/TMBIM6 signaling axis in the progression of DN was elucidated. Type 2 diabetic db/db mice and high glucose (HG)-challenged HK-2 cells were used as in vivo and in vitro models. Our results showed that miR-27a-3p was upregulated and prohibitin or transmembrane BAX inhibitor motif containing 6 (TMBIM6) was downregulated in the kidney tissues of db/db mice and HG-treated HK-2 cells. Silencing miR-27a-3p enhanced the expression of prohibitin and TMBIM6 in the kidney tissues and HK-2 cells. Inhibition of miR-27a-3p improved functional injury, as evidenced by decreased blood glucose, urinary albumin, serum creatinine, and blood urea nitrogen levels. MiR-27a-3p silencing ameliorated renal fibrosis, reflected by reduced profibrogenic genes (e.g., transforming growth factor ß1, fibronectin, collagen I and III, and α-smooth muscle actin). Furthermore, inhibition of miR-27a-3p relieved mitochondrial dysfunction in the kidney of db/db mice, including upregulation of mitochondrial membrane potential, complex I and III activities, adenosine triphosphate, and mitochondrial cytochrome C, as well as suppressing reactive oxygen species production. In addition, miR-27a-3p silencing attenuated endoplasmic reticulum (ER) stress, reflected by reduced expression of p-IRE1α, p-eIF2α, XBP1s, and CHOP. Mechanically, we identified prohibitin and TMBIM6 as direct targets of miR-27a-3p. Inhibition of miR-27a-3p protected HG-treated HK-2 cells from apoptosis, extracellular matrix accumulation, mitochondrial dysfunction, and ER stress by regulating prohibitin or TMBIM6. Taken together, we reveal that miR-27a-3p-prohibitin/TMBIM6 signaling axis regulates the progression of DN, which can be a potential therapeutic target.

Three-Dimensional Triptycene-Based Covalent Organic Frameworks with ceq or acs Topology.

The growth of three-dimensional covalent organic frameworks (3D COFs) with new topologies is still considered as a great challenge due to limited availability of high-connectivity building units. Here we report the design and synthesis of 3D triptycene-based COFs, termed JUC-568 and JUC-569, following the deliberate symmetry-guided design principle. By combining a triangular prism (6-connected) node with a planar triangle (3-connected) or another triangular prism node, the targeted COFs adopt non-interpenetrated ceq or acs topology, respectively. Both materials show permanent porosity and impressive performance in the adsorption of CO2 (∼98 cm3/g at 273 K and 1 bar), CH4 (∼48 cm3/g at 273 K and 1 bar), and especially H2 (up to 274 cm3/g or 2.45 wt % at 77 K and 1 bar), which is highest among porous organic materials reported to date. This research thus provides a promising strategy for diversifying 3D COFs based on complex building blocks and promotes their potential applications in energy storage and environment-related fields.

3D Thioether-Based Covalent Organic Frameworks for Selective and Efficient Mercury Removal.

Developing functionalized 3D covalent organic frameworks (3D COFs) is critical to broaden their potential applications. However, the introduction of specific functionality in 3D COFs remains a great challenge because most of the functional groups are not compatible with the synthesis conditions. Herein, for the first time 3D thioether-based COFs (JUC-570 and JUC-571) for mercury (Hg2+ ) removal from aqueous solution is reported. These 3D thioether-based COFs prepared by the bottom-up approach display high Hg2+ uptakes (972 mg g-1 for JUC-570 and 970 mg g-1 for JUC-571 at pH = 5), fast adsorption kinetics (distribution coefficient Kd value of 2.29 × 107  mL g-1 for JUC-570 and 2.07 × 107  mL g-1 for JUC-571), and favorable selectivity. In particular, JUC-570 is periodically decorated with isopropyl groups around imine bonds that markedly improve its chemical stability and effectively prevent the pore collapse, and thus endows high Hg2+ adsorption capacity (619 mg g-1 ) and excellent cycle performance even at pH = 1. This study not only puts forward a new route to construct stable functionalized 3D COFs, but also promotes their potential applications in areas related to the environment.

3D Hydrazone-Functionalized Covalent Organic Frameworks as pH-Triggered Rotary Switches.

The property expansion of 3D functionalized covalent organic frameworks (COFs) is important for developing their potential applications. Herein, the first case of 3D hydrazone-decorated COFs as pH-triggered molecular switches is reported, and their application in the stimuli-responsive drug delivery system is explored. These functionalized COFs with hydrazone groups on the channel walls are obtained via a multi-component bottom-up synthesis strategy. They exhibit a reversible E/Z isomerization at various pH values, confirmed by UV-vis absorption spectroscopy and proton conduction. Remarkably, after loading cytarabine (Ara-C) as a model drug molecule, these pH-responsive COFs show an excellent and intelligent sustained-release effect with an almost fourfold increase in the Ara-C release at pH = 4.8 than at pH = 7.4, which will effectively improve drug-targeting. Thus, these results open a way toward designing 3D stimuli-responsive functionalized COF materials and promote their potential application as drug carriers in the field of disease treatment.

Three-Dimensional Radical Covalent Organic Frameworks as Highly Efficient and Stable Catalysts for Selective Oxidation of Alcohols.

With excellent designability, large accessible inner surface, and high chemical stability, covalent organic frameworks (COFs) are promising candidates as metal-free heterogeneous catalysts. Here, we report two 3D radical-based COFs (JUC-565 and JUC-566) in which radical moieties (TEMPO) are uniformly decorated on the channel walls via a bottom-up approach. Based on grafted functional groups and suitable regular channels, these materials open up the application of COFs as highly efficient and selective metal-free redox catalysts in aerobic oxidation of alcohols to relevant aldehydes or ketones with outstanding turn over frequency (TOF) up to 132 h-1 , which has exceeded other TEMPO-modified catalytic materials tested under similar conditions. These stable COF-based catalysts could be easily recovered and reused for multiple runs. This study promotes potential applications of 3D functional COFs anchored with stable radicals in organic synthesis and material science.

Three-Dimensional Mesoporous Covalent Organic Frameworks through Steric Hindrance Engineering.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with large pores and high surface areas is of great importance for various applications. However, it remains a major challenge due to the frequent structural interpenetration and pore collapse after the removal of guest species situated in the pores. Herein, we report for the first time a series of 3D mesoporous COFs through a general method of steric hindrance engineering. By placing methoxy and methyl groups strategically on the monomers, we can obtain non-interpenetrated 3D COFs of diamondoid structures with permanent mesopores (up to 26.5 Å) and high surface areas (>3000 m2 g-1), which are far superior to those of reported conventional COFs with the same topology. This work thus opens a new avenue to create 3D large-pore COFs for potential applications in adsorption and separation of large inorganic, organic, and biological molecules.

Three-Dimensional Large-Pore Covalent Organic Framework with stp Topology.

Three-dimensional (3D) covalent organic frameworks (COFs) are excellent crystalline porous polymers for numerous potential applications, but their building units and topological nets have been limited. Herein we report the design and synthesis of the first 3D large-pore COF with the stp topology constructed from a 6-connected triptycene-based monomer. The new COF (termed JUC-564) has a high specific surface area (up to 3300 m2 g-1), the largest pore size among 3D COFs (43 Å), and record-breaking low density among crystalline materials reported to date (0.108 g cm-3). The large pore size of JUC-564 was confirmed by the incorporation of a protein. This study expands the structural varieties of 3D COFs based on the deliberate symmetry-guided design principle as well as their applications for adsorption and separation of large biological molecules.

Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice.

Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3ß (pSer9-GSK3ß) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.

Three-Dimensional Chemically Stable Covalent Organic Frameworks through Hydrophobic Engineering.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with high chemical stability is of critical importance for their practical use. In this work, it is demonstrated that the stability of 3D COFs can be improved by periodic decoration of isopropyl groups on their backbones. Owing to the strong hydrophobicity of the alkyl groups, the resultant COFs show high crystallinity, permanent pores, and exceptional stability in harsh environments, such as strong acids (3 m HCl or 3 m H2 SO4 for one week), a strong base (20 m NaOH for one week), and boiling water (100 °C for one month). Furthermore, these highly stable and hydrophobic COFs display excellent oil/water separation performance with >99 % separation efficiency over a wide pH range. This work demonstrates the use of alkyl decoration in 3D COFs to tune their chemical stability and expand their potential applications.

Solvent-Free Secondary Growth of Highly b-Oriented MFI Zeolite Films from Anhydrous Synthetic Powder.

Up to date, zeolite films have been mainly fabricated by in situ crystallization, secondary growth in a solution/hydrogel, or occasionally by vapor phase transformation of dry gel. Here we demonstrate for the first time a solvent-free secondary growth method for b-oriented silica MFI zeolite films using the synthetic powder from ground anhydrous raw solids in the presence of NH4F. Typically, precisely b-oriented MFI zeolite films are synthesized from seed layers of highly b-oriented MFI zeolite crystals in the synthetic powder of 1SiO2:0.035TPABr:0.05NH4F at 175 °C for 6 h. If needed, b-oriented MFI zeolite multilayer films can be acquired by changing the synthesis time or the amount of NH4F in the synthetic powder. Compared with the traditional hydrothermal synthesis, the approach developed here may provide a new avenue for fabricating high quality zeolite films/membranes.

Three-dimensional Salphen-based Covalent-Organic Frameworks as Catalytic Antioxidants.

The development of three-dimensional (3D) functionalized covalent-organic frameworks (COFs) is of critical importance for expanding their potential applications. However, the introduction of functional groups in 3D COFs remains largely unexplored. Herein, we report the first example of 3D Salphen-based COFs (3D-Salphen-COFs) and their metal-containing counterparts (3D-M-Salphen-COFs). These Salphen-based COFs exhibit high crystallinity and specific surface area in addition to excellent chemical stability. Furthermore, the Cu(II)-Salphen COF displays high activity in the removal of superoxide radicals. This study not only presents a new pathway to construct 3D functionalized COFs but also promotes their applications in biology and medicine.