Engineering asymmetric electronic structure of cobalt coordination on CoN_(3)S active sites for high performance oxygen reduction reaction

The efficacy of the oxygen reduction reaction(ORR) in fuel cells can be significantly enhanced by optimizing cobalt-based catalysts,which provide a more stable alternative to iron-based catalysts.However,their performance is often impeded by weak adsorption of oxygen species,leading to a 2e^(-)pathway that negatively affects fuel cell discharge efficiency.Here,we engineered a high-density cobalt active center catalyst,coordinated with nitrogen and sulfur atoms on a porous carbon substrate.Both experimental and theoretical analyses highlighted the role of sulfur atoms as electron donors,disrupting the charge symmetry of the original Co active center and promoting enhanced interaction with Co 3d orbitals.This modification improves the adsorption of oxygen and reaction intermediates during ORR,significantly reducing the production of hydrogen peroxide(H_(2)O_(2)).Remarkably,the optimized catalyst demonstrated superior fuel cell performance,with peak power densities of 1.32 W cm^(-2) in oxygen and 0.61 W cm^(-2) in air environments,respectively.A significant decrease in H_(2)O_(2) by-product accumulation was observed during the reaction process,reducing catalyst and membrane damage and consequently improving fuel cell durability.This study emphasizes the critical role of coordination symmetry in Co/N/C catalysts and proposes an effective strategy to enhance fuel cell performance.

Boost the Utilization of Dense FeN_(4) Sites for High-Performance Proton Exchange Membrane Fuel Cells

Iron-nitrogen-carbon(Fe-N-C)catalysts for the oxygen reduction reaction(ORR)in proton exchange membrane fuel cells(PEMFCs)have seriously been hindered by their poor ORR performance of Fe-N-C due to the low active site density(SD)and site utilization.Herein,we reported a melamine-assisted vapor deposition approach to overcome these hindrances.The melamine not only compensates for the loss of nitrogen caused by high-temperature pyrolysis but also effectively etches the carbon substrate,increasing the external surface area and mesoporous porosity of the carbon substrate.These can provide more useful area for subsequent vapor deposition on active sites.The prepared 0.20Mela-FeNC catalyst shows a fourfold higher SD value and site utilization than the FeNC without the treatment of melamine.As a result,0.20Mela-FeNC catalyst exhibits a high ORR activity with a half-wave potential(E_(1/2))of 0.861 V and 12-fold higher ORR mass activity than the FeNC in acidic media.As the cathode in a H_(2)-O_(2)PEMFCs,0.20Mela-FeNC catalyst demonstrates a high peak power density of 1.30 W cm^(-2),outstripping most of the reported Fe-N-C catalysts.The developed melamine-assisted vapor deposition approach for boosting the SD and utilization of Fe-N-C catalysts offers a new insight into high-performance ORR electrocatalysts.

Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors

P2X receptors are a family of extracellular ATP-gated trimeric cation channels that is widely distributed in human tissues. Quite some drug candidates targeting P2X receptors have entered into preclinical or main phases of clinical trials, but many of them failed due to low subtype-selectivity or species differences in pharmacological activities between human and experimental animals. Here, we identified the distinct inhibitory efficacies of NF110, a competitive inhibitor, between the rat(rP2X3) and human(hP2X3) P2X3 receptors. We demonstrated that this difference is determined by two amino acids located in the dorsal fin(DF) domain of P2X3 receptors. As revealed by mutagenesis, metadynamics, and covalent modification, NF110-mediated rP2X3 inhibition may be through a filling in the cavity formed by the DF,left flipper(LF) and lower body(LB) to partially, rather than fully, occupy the ATP-binding pocket.Moreover, substitution of residues located in the DF and/or LF domains of the rP2X2 receptor, a NF110-insensitive subtype, with the equivalent amino acids of rP2X3, bestowed the sensitivity of rP2X2 to NF110. The critical roles of the DF and LF domains in channel gating of P2X and low conservativity in residue sequences of those two domains raise the possibility that small molecules differentially interacting with the residues of the DF and LF domains of different P2X receptors may modulate channel's activity in a subtype-selective manner. However, the possible species-specificity of P2X inhibitors/modulators makes it more complex when interpreting the preclinical data into clinical researches.Nevertheless, our data provide new insights into the subtype-selectivity of competitive inhibitors and their distinct potencies in the human and experimental animals, both of which are extremely important in the drug discovery of P2X receptors.

Degradable Hybrid CuS Nanoparticles for Imaging-Guided Synergistic Cancer Therapy via Low-Power NIR-II Light Excitation

Near-infrared(NIR)-II light-excitable photonic agents capable of generating tumor hyperthermia and cytotoxic free radicals are promising for synergistic phototherapy of tumors.However,the lack of NIR-II excitable agents makes it challenging to achieve combinational tumor phototherapy.Here,the authors have reported on a tumor-targeting and degradable hybrid copper sulfide(CuS)nanoparticle(AIBA@CuS-FA)via loading a hydrophilic Azo initiator(AIBA)into an amphiphilic lipid-encapsulating CuS nanoparticle.AIBA@CuS-FA shows high photothermal conversion efficiency(PCE≈47.5%)at 1064 nm,enabling heat production to trigger tumor hyperthermia and thermal decomposition of AIBA into cytotoxic free alkyl radicals upon irradiation with a 1064-nm laser under low-power density(0.5 W/cm2).Moreover,alkyl radicals can drive degradation of AIBA@CuS-FA and embedded CuS nanodisks,releasing Cu^(2+)ions that can catalyze a Fenton-like reaction for hydroxyl radical(•OH)production to promote tumor therapy.Findings demonstrate promise for combinational photothermal therapy(PTT),oxygen-independent alkyl radical therapy,and chemodynamic therapy(CDT)of tumors.

Responsive Trimodal Probes for In Vivo Imaging of Liver Inflammation by Coassembly and GSH-Driven Disassembly

Noninvasive in vivo imaging of hepatic glutathione(GSH)levels is essential to early diagnosis and prognosis of acute hepatitis.Although GSH-responsive fluorescence imaging probes have been reported for evaluation of hepatitis conditions,the low penetration depth of light in liver tissue has impeded reliable GSH visualization in the human liver.We present a liver-targeted and GSH-responsive trimodal probe(GdNPs-Gal)for rapid evaluation of lipopolysaccharide-(LPS-)induced acute liver inflammation via noninvasive,real-time in vivo imaging of hepatic GSH depletion.GdNPs-Gal are formed by molecular coassembly of a GSH-responsive Gd(III)-based MRI probe(1-Gd)and a liver-targeted probe(1-Gal)at a mole ratio of 5/1(1-Gd/1-Gal),which shows high r_(1) relaxivity with low fluorescence and fluorine magnetic resonance spectroscopic(^(19)F-MRS)signals.Upon interaction with GSH,1-Gd and 1-Gal are cleaved and GdNPs-Gal rapidly disassemble into small molecules 2-Gd,2-Gal,and 3,producing a substantial decline in r_(1) relaxivity with compensatory enhancements in fluorescence and ^(19)F-MRS.By combining in vivo magnetic resonance imaging(^(1)H-MRI)with ex vivo fluorescence imaging and ^(19)F-MRS analysis,GdNPs-Gal efficiently detect hepatic GSH using three independent modalities.We noninvasively visualized LPS-induced liver inflammation and longitudinally monitored its remediation in mice after treatment with an anti-inflammatory drug,dexamethasone(DEX).Findings highlight the potential of GdNPs-Gal for in vivo imaging of liver inflammation by integrating molecular coassembly with GSH-driven disassembly,which can be applied to other responsive molecular probes for improved in vivo imaging.