Synergistic Linker and Linkage of Covalent Organic Frameworks for Enhancing Gold Capture.

The tunable pore walls and skeletons render covalent organic frameworks (COFs) as promising absorbents for gold (Au) ion. However, most of these COFs suffered from low surface areas hindering binding sites exposed and weak binding interaction resulting in sluggish kinetic performance. In this study, COFs have been constructed with synergistic linker and linkage for high-efficiency Au capture. The designed COFs (PYTA-PZDH-COF and PYTA-BPDH-COF) with pyrazine or bipyridine as linkers showed high surface areas of 1692 and 2076 m2 g‒1, providing high exposed surface areas for Au capture. In addition, the Lewis basic nitrogen atoms from the linkers and linkages are easily hydronium, which enabled to fast trap Au via coulomb force. The PYTA-PZDH-COF and PYTA-BPDH-COF showed maximum Au capture capacities of 2314 and 1810 mg g-1, higher than other reported COFs. More importantly, PYTA-PZDH-COF are capable of rapid adsorption kinetics with achieving 95% of maximum binding capacity in 10 min. The theoretical calculation revealed that the nitrogen atoms in linkers and linkages from both COFs are simultaneously hydronium, and then the protonated PYTA-PZDH-COF are more easily binding the AuCl4 ‒, further accelerating the binding process. This study gives the a new insight to design COFs for ion capture.

Ionic Covalent Organic Frameworks in Adsorption and Catalysis.

The ion extraction and electro/photo catalysis are promising methods to address environmental and energy issues. Covalent organic frameworks (COFs) are a class of promising template to construct absorbents and catalysts because of their stable frameworks, high surface areas, controllable pore environments, and well-defined catalytic sites. Among them, ionic COFs as unique class of crystalline porous materials, with charges in the frameworks or along the pore walls, have shown different properties and resulting performance in these applications with those from charge-neutral COFs. In this review, current research progress based on the ionic COFs for ion extraction and energy conversion, including cationic/anionic materials and electro/photo catalysis is reviewed in terms of the synthesis strategy, modification methods, mechanisms of adsorption and catalysis, as well as applications. Finally, we demonstrated the current challenges and future development of ionic COFs in design strategies and applications.

Upregulation of CIRP by its agonist prevents the development of heart failure in myocardial infarction rats.

BACKGROUND: Downregulated expression of cold-inducible RNA binding protein (CIRP), a stress-response protein, has been demonstrated in the hearts of patients with heart failure (HF). However, whether CIRP plays a critical role in the pathogenesis of HF remains unknown. Zr17-2 is a recently identified CIRP agonist, which can enhance the expression of CIRP in hearts. Herein, we evaluated the effects of zr17-2 on the development of HF in a rat model of myocardial infarction (MI). METHODS: Male SD rats were pretreated with CIRP agonist zr17-2 or vehicle saline for 6 consecutive days, followed by MI induction. 1-week post-MI, cardiac function, and structural and molecular changes were determined by echocardiography and molecular biology methods. RESULTS: Excitingly, we found that pretreatment with zr17-2 significantly attenuated MI-induced cardiac dysfunction and dilation, coupled with reduced infarction size and cardiac remodeling. In addition, increased inflammatory response in the peri-infarcted heart including macrophage infiltration and the expression of inflammatory genes were all significantly decreased by zr17-2 pretreatment, suggesting an anti-inflammatory effect of zr17-2. Moreover, zr17-2 pretreatment also upregulated the antioxidant genes (e.g. NQO-1, Nrf2, and HO-1) level in the hearts. In isolated cultured cardiomyocytes, pretreatment with zr17-2 markedly attenuated cell injury and apoptosis induced by oxidative injury, along with elevation of Nrf2-related antioxidant genes and CIRP. However, silencing CIRP abolished zr17-2's antioxidant effects against oxidative injury, confirming that zr17-2's role is dependent on CIRP. CONCLUSION: Collectively, our study suggests CIRP plays a crucial role in the development of HF and a beneficial effect of CIRP agonist in preventing MI-induced HF, possibly via anti-inflammatory and anti-oxidant pathways.

Elaborate Modulating Binding Strength of Intermediates via Three-component Covalent Organic Frameworks for CO2 Reduction Reaction.

The catalytic performance for electrocatalytic CO2 reduction reaction (CO2RR) depends on the binding strength of the reactants and intermediates. Covalent organic frameworks (COFs) have been adopted to catalyze CO2RR, and their binding abilities are tuned via constructing donor-acceptor (DA) systems. However, most DA COFs have single donor and acceptor units, which caused wide-range but lacking accuracy in modulating the binding strength of intermediates. More elaborate regulation of the interactions with intermediates are necessary and challenge to construct high-efficiency catalysts. Herein, the three-component COF with D-A-A units was first constructed by introducing electron-rich diarylamine unit, electron-deficient benzothiazole and Co-porphyrin units. Compared with two-component COFs, the designed COF exhibit elevated electronic conductivity, enhanced reducibility, high efficiency charge transfer, further improving the electrocatalytic CO2RR performance with the faradic efficiency of 97.2 % at -0.8 V and high activity with the partial current density of 27.85 mA cm-2 at -1.0 V which exceed other two-component COFs. Theoretical calculations demonstrate that catalytic sites in three-component COF have suitable binding ability of the intermediates, which are benefit for formation of *COOH and desorption of *CO. This work offers valuable insights for the advancement of multi-component COFs, enabling modulated charge transfer to improve the CO2RR activity.

3D Crown Ether Covalent Organic Framework as Interphase Layer toward High-Performance Lithium Metal Batteries.

The practical application of lithium (Li) metal batteries is inhibited by accumulative Li dendrites and continuous active Li consumption during cycling, which results in a low Coulombic efficiency and short lifetime. Constructing artificial solid-electrolyte interphase (SEI) layer in Li anode, such as 2D covalent organic frameworks (COFs), is an effective strategy to restrain the formation of Li dendrites and improve cycling performance. However, the exploration of 3D COFs as protecting layers is rarely reported, because of the preconception that the interconnect pores in 3D COFs eventually cause Li dendrites in disordered direction. 3D crown ether-based COF with ffc topology as interphase layer, in which the crown ether units are arranged in parallel and vertical orientation along the electrode, is demonstrated. The strong coupling effect between the crown ether and Li+ accelerates Li+ diffusion kinetics and enables homogeneous Li+ flux, resulting in a high Li+ transference number of 0.85 and smooth Li deposition in 3D direction. Li/COF-Cu cells display a lower Li-nucleation overpotential (17.4 mV) and high average Coulombic efficiency of ≈98.6% during 340 cycles with COF incorporation. This work gives a new insight into designing COFs for energy storage systems.

Solvent Effects on Metal-free Covalent Organic Frameworks in Oxygen Reduction Reaction.

Binding water molecules to polar sites in covalent organic frameworks (COFs) is inevitable, but the corresponding solvent effects in electrocatalytic process have been largely overlooked. Herein, we investigate the solvent effects on COFs for catalyzing the oxygen reduction reaction (ORR). Our designed COFs incorporated different kinds of nitrogen atoms (imine N, pyridine N, and phenazine N), enabling tunable interactions with water molecules. These interactions play a crucial role in modulating electronic states and altering the catalytic centers within the COFs. Among the synthesized COFs, the one with pyridine N atoms exhibits the highest activity, with characterized by a half-wave potential of 0.78 V and a mass activity of 0.32 A mg-1, which surpass those from other metal-free COFs. Theoretical calculations further reveal that the enhanced activity can be attributed to the stronger binding ability of *OOH intermediates to the carbon atoms adjacent to the pyridine N sites. This work sheds light on the significance of considering solvent effects on COFs in electrocatalytic systems, providing valuable insights into their design and optimization for improved performance.

Charging modulation of the pyridine nitrogen of covalent organic frameworks for promoting oxygen reduction reaction.

Covalent organic frameworks (COFs) are ideal templates for constructing metal-free catalysts for the oxygen reduction reaction due to their highly tuneable skeletons and controllable porous channels. However, the development of highly active sites within COFs remains challenging due to their limited electron-transfer capabilities and weak binding affinities for reaction intermediates. Herein, we constructed highly active catalytic centres by modulating the electronic states of the pyridine nitrogen atoms incorporated into the frameworks of COFs. By incorporating different pyridine units (such as pyridine, ionic pyridine, and ionic imidazole units), we tuned various properties including dipole moments, reductive ability, hydrophilicity, and binding affinities towards reaction intermediates. Notably, the ionic imidazole COF (im-PY-BPY-COF) exhibited greater activity than the neutral COF (PY-BPY-COF) and ionic pyridine COF (ion-PY-BPY-COF). Specifically, im-PY-BPY-COF demonstrated a half-wave potential of 0.80 V in 0.1 M KOH, outperforming other metal-free COFs. Theoretical calculations and in situ synchrotron radiation Fourier transform infrared spectroscopy confirmed that the carbon atoms in the ionic imidazole rings improved the activity by facilitating binding of the intermediate OOH* and promoting the desorption of OH*. This study provides new insights into the design of highly active metal-like COF catalysts.

Alkadiyne-Pyrene Conjugated Frameworks with Surface Exclusion Effect for Ultrafast Seawater Desalination.

Billions of populations are suffering from the supply-demand imbalance of clean water, resulting in a global sustainability crisis. Membrane desalination is a promising method to produce fresh water from saline waters. However, conventional membranes often encounter challenges related to low water permeation, negatively impacting energy efficiency and water productivity. Herein, we achieve ultrafast desalination over the newly developed alkadiyne-pyrene conjugated frameworks membrane supported on a porous copper hollow fiber. With membrane distillation, the membrane exhibits nearly complete NaCl rejection (>99.9%) and ultrahigh fluxes (∼500 L m-2 h-1) from the seawater salinity-level NaCl solutions, which surpass the commercial polymeric membranes with at least 1 order of magnitude higher permeability. Experimental and theoretical investigations suggest that the large aspect ratio of membrane pores and the high evaporation area contribute to the high flux, and the graphene-like hydrophobic surface of conjugated frameworks exhibits complete salt exclusion. The simulations also confirm that the intraplanar pores of frameworks are impermeable for water and ions.

Modulating Skeletons of Covalent Organic Framework for High-Efficiency Gold Recovery.

Covalent organic frameworks (COFs) have attracted considerable attention as adsorbents for capturing and separating gold from electronic wastes. To enhance the binding capture efficiency, constructing hydrogen-bond nanotraps along the pore walls was one of the most widely adopted approaches. However, the development of absorbing skeletons was ignored due to the weak binding ability of the gold salts (Au). Herein, we demonstrated skeleton engineering to construct highly efficiently absorbs for Au capture. The strong electronic donating feature of diarylamine units enhanced the electronic density of binding sites (imine-linkage) and thus resulted in high capacities over 1750 mg g-1 for all three COFs. Moreover, the absorbing performance was further improved via the ionization of diarylamine units. The ionic COF achieved 90 % of the maximal adsorption capacity, 1.63 times of that from the charge-neutral COF within ten minutes, and showed remarkable uptakes of 1834 mg g-1 , exceptional selectivity (97.45 %) and cycling stability. The theoretical calculation revealed the binding sites altering from imine bonds to ionic amine sites after ionization of the frameworks, which enabled to bind the AuCl4 - via coulomb force and contributed to enhanced absorbing kinetics. This work inspires us to design molecular/ionic capture based on COFs.

Quantitative Construction of Boronic-Ester Linkages in Covalent Organic Frameworks for the Carbon Dioxide Reduction.

Covalent organic frameworks (COFs) have been utilized for catalyzing the reduction of carbon dioxide (CO2RR) due to their atomic metal centers and controllable pore channels, which are facilitated by different covalent bonds. However, the exploration of boron-based linkages in these catalytic COFs has been limited owing to potential instability. Herein, we present the construction of boronic ester-linked COFs through nucleophilic substitution reactions in order to catalyze the CO2 RR. The inclusion of abundant fluorine atoms within the frameworks enhances their hydrophobicity and subsequently improves water tolerance and chemical stability of COFs. The content of boron atoms in the COF linkages was carefully controlled, with COFs featuring a higher density of boron atoms exhibiting increased electronic conductivity, enhanced reductive ability, and stronger binding affinity towards CO2 . Consequently, these COFs demonstrate improved activity and selectivity. The optimized COFs achieve the highest activity, achieving a turnover frequency of 1695.3 h-1 and a CO selectivity of 95.0 % at -0.9 V. Operando synchrotron radiation measurements confirm the stability of Co (II) atoms as catalytically active sites. By successfully constructing boronic ester-linked COFs, we not only address potential instability concerns but also achieve exceptional catalytic performance for CO2 RR.

Confined Synthesis of Dual-Atoms Within Pores of Covalent Organic Frameworks for Oxygen Reduction Reaction.

Dual-atom catalysts exhibit higher reactivity and selectivity than the single-atom catalysts. The pyrolysis of bimetal salt precursors is the most typical method for synthesizing dual-atomic catalysts; however, the finiteness of bimetal salts limits the variety of dual-atomic catalysts. In this study, a confined synthesis strategy for synthesizing dual-atomic catalysts is developed. Owing to the in situ synthesis of zeolitic imidazolate frameworks in the pores of covalent organic frameworks (COFs), the migration and aggregation of metal atoms are suppressed adequately during the pyrolysis process. The resultant catalyst contains abundant Zn─Co dual atomic sites with 2.8 wt.% Zn and 0.5 wt.% Co. The catalyst exhibits high reactivity toward oxygen reduction reaction with a half-wave potential of 0.86 V, which is superior to that of the commercial Pt/C catalyst. Theoretical calculations reveal that the Zn atoms in the Zn─Co dual atomic sites promote the formation of intermediate OOH*, and thus contribute to high catalytic performance. This study provides new insights into the design of dual-atom catalysts using COFs.

Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury.

Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by γδ T cells. FMT regulated γδ T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17+ γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.

Construction of Core-Shelled Covalent/Metal-Organic Frameworks for Oxygen Evolution Reaction.

Oxygen evolution reaction (OER) is the half-reaction in zinc-air batteries and water splitting. Developing highly efficient catalysts toward OER is a challenge due to the difficulty of removing four electrons from two water molecules. Covalent organic frameworks (COFs) provide the new chance to construct the highly active catalysts for OER, because they have controlled skeletons, porosities, and well-defined catalytic sites. In this work, core-shell hybrids of COF and metal-organic frameworks (MOFs) have first demonstrated to catalyze the OER. The synergetic effects between the COF-shell and MOF-core render the catalyst with higher activity than those from the COF and MOF. And the catalyst achieved an overpotential of 328 mV, with a Tafel slope of 43.23 mV dec-1 in 1 m KOH. The theoretical calculation revealed that the high activity is from the Fe sites in the catalyst, which has suitable binding ability of reactant intermediate (OOH* ), and thus contributed high activity. This work gives a new insight to designing COFs in electrochemical energy storage and conversion systems.

Conditional knockout of PDK1 in osteoclasts suppressed osteoclastogenesis and ameliorated prostate cancer-induced osteolysis in murine model.

BACKGROUND: The development and maintenance of normal bone tissue is maintained by balanced communication between osteoblasts and osteoclasts. The invasion of cancer cells disrupts this balance, leading to osteolysis. As the only bone resorbing cells in vivo, osteoclasts play important roles in cancer-induced osteolysis. However, the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in osteoclast resorption remains unclear. METHODS: In our study, we used a receptor activator of nuclear factor-kappa B (RANK) promoter-driven Cre-LoxP system to conditionally delete the PDK1 gene in osteoclasts in mice. We observed the effect of osteoclast-specific knockout of PDK1 on prostate cancer-induced osteolysis. Bone marrow-derived macrophage cells (BMMs) were extracted and induced to differentiate osteoclasts in vitro to explore the role of PDK1 in osteoclasts. RESULTS: In this study, we found that PDK1 conditional knockout (cKO) mice exhibited smaller body sizes when compared to the wild-type (WT) mice. Moreover, deletion of PDK1 in osteoclasts ameliorated osteolysis and rPDK1educed bone resorption markers in the murine model of prostate cancer-induced osteolysis. In vivo, we discovered that osteoclast-specific knockout of suppressed RANKL-induced osteoclastogenesis, bone resorption function, and osteoclast-specific gene expression (Ctsk, TRAP, MMP-9, NFATc1). Western blot analyses of RANKL-induced signaling pathways showed that conditional knockout of PDK1 in osteoclasts inhibited the early nuclear factor κB (NF-κB) activation, which consequently suppressed the downstream induction of NFATc1. CONCLUSION: These findings demonstrated that PDK1 performs an important role in osteoclastogenesis and prostate cancer-induced osteolysis by modulating the PDK1/AKT/NF-κB signaling pathway.

Modulating the Density of Catalytic Sites in Multiple-Component Covalent Organic Frameworks for Electrocatalytic Carbon Dioxide Reduction.

It is generally assumed that the more metal atoms in covalent organic frameworks (COFs) contribute to higher activity toward electrocatalytic carbon dioxide reduction (CO2RR) and hindered us in exploring the correlation between the density of catalytic sites and catalytic performances. Herein, we have constructed quantitative density of catalytic sites in multiple COFs for CO2RR, in which the contents of phthalocyanine (H2Pc) and nickel phthalocyanine (NiPc) units were preciously controlled. With a molar ratio of 1/1 for the H2Pc and NiPc units in COFs, the catalyst achieved the highest selectivity with a carbon monoxide Faradaic efficiency (FECO) of 95.37% and activity with a turnover frequency (TOF) of 4713.53 h-1. In the multiple H2Pc/NiPc-COFs, the electron-donating features of the H2Pc units provide electron transport to the NiPc centers and thus improved the binding ability of CO2 and intermediates on the NiPc units. The theoretical calculation further confirmed that the H2Pc units donated their electrons to the NiPc units in the frameworks, enhanced the electron density of the Ni sites, and improved the binding ability with Lewis acidic CO2 molecules, thereby boosting the CO2RR performance. This study provides us with new insight into the design of highly active catalysts in electrocatalytic systems.

Post-synthetic modification of covalent organic frameworks for CO2 electroreduction.

To achieve high-efficiency catalysts for CO2 reduction reaction, various catalytic metal centres and linker molecules have been assembled into covalent organic frameworks. The amine-linkages enhance the binding ability of CO2 molecules, and the ionic frameworks enable to improve the electronic conductivity and the charge transfer along the frameworks. However, directly synthesis of covalent organic frameworks with amine-linkages and ionic frameworks is hardly achieved due to the electrostatic repulsion and predicament for the strength of the linkage. Herein, we demonstrate covalent organic frameworks for CO2 reduction reaction by modulating the linkers and linkages of the template covalent organic framework to build the correlation between the catalytic performance and the structures of covalent organic frameworks. Through the double modifications, the CO2 binding ability and the electronic states are well tuned, resulting in controllable activity and selectivity for CO2 reduction reaction. Notably, the dual-functional covalent organic framework achieves high selectivity with a maximum CO Faradaic efficiency of 97.32% and the turnover frequencies value of 9922.68 h-1, which are higher than those of the base covalent organic framework and the single-modified covalent organic frameworks. Moreover, the theoretical calculations further reveal that the higher activity is attributed to the easier formation of immediate *CO from COOH*. This study provides insights into developing covalent organic frameworks for CO2 reduction reaction.

CTRP5 Attenuates Doxorubicin-Induced Cardiotoxicity Via Inhibiting TLR4/NLRP3 Signaling.

BACKGROUND: C1q/tumor necrosis factor-related protein 5 (CTRP5) has been reported to be a crucial regulator in cardiac ischemia/reperfusion (I/R) injury. Nevertheless, the potential role of CTRP5 in doxorubicin (DOX)-induced cardiotoxicity and the potential mechanisms remain largely unclear. METHODS: We overexpressed CTRP5 in the hearts using an adeno-associated virus 9 (AAV9) system through tail vein injection. C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity for 4 weeks. Subsequently, cardiac staining and molecular biological analysis were performed to analyze the morphological and biochemical effects of CTRP5 on the cardiac injury. H9c2 cells were used for validation in vitro. RESULTS: CTRP5 expression was down-regulated after DOX treatment both in vivo and in vitro. CTRP5 overexpression significantly attenuated DOX-induced cardiac injury, cardiac dysfunction, inhibited oxidative stress and inflammatory response. Mechanistically, CTRP5 overexpression markedly decreased the protein expression of toll-like receptor 4 (TLR4), NLRP3, cleaved caspase-1 and caspase-1, indicating TLR/NLRP3 signaling contributes to the cardioprotective role of CTRP5 in DOX-induced cardiotoxicity. CONCLUSIONS: Together, our findings demonstrated that CTRP5 overexpression could protect the heart from oxidative stress and inflammatory injury induced by DOX through inhibiting TLR4/NLRP3 signaling, suggesting that CTRP5 might be a potential therapeutic target in the prevention of DOX-induced cardiotoxicity.

Catalytic Linkage Engineering of Covalent Organic Frameworks for the Oxygen Reduction Reaction.

Metal-free covalent organic frameworks (COFs) have been employed to catalyze the oxygen reduction reaction (ORR). To achieve high activity and selectivity, various building blocks containing heteroatoms and groups linked by imine bonds were used to create catalytic COFs. However, the roles of linkages of COFs in ORR have not been investigated. In this work, the catalytic linkage engineering has been employed to modulate the catalytic behaviors. To create single catalytic sites while avoiding other possible catalytic sites, we synthesized COFs from benzene units linked by various bonds, such as imine, amide, azine, and oxazole bonds. Among these COFs, the oxazole-linkage in COFs enables to catalyze the ORR with the highest activity, which achieved a half-wave potential of 0.75 V and a limited current density of 5.5 mA cm-2 . Moreover, the oxazole-linked COF achieved a conversion frequency (TOF) value of 0.0133 S-1 , which were 1.9, 1.3, and 7.4-times that of azine-, amide- and imine-COFs, respectively. The theoretical calculation showed that the carbon atoms in oxazole linkages facilitated the formation of OOH* and promoted protonation of O* to form the OH*, thus advancing the catalytic activity. This work guides us on which linkages in COFs are suitable for ORR.