Oxygen Vacancy-Mediated Synthesis of Inter-Atomically Ordered Ultrafine Pt-Alloy Nanoparticles for Enhanced Fuel Cell Performance.

Pt-based intermetallics are expected to be the highly active catalysts for oxygen reduction reaction (ORR) in proton-exchange membrane fuel cells but still face great challenges in controllable synthesis of interatomically ordered and ultrafine intermetallic nanoparticles. Here, we propose an oxygen vacancy-mediated atomic diffusion strategy by mechanical alloying to reduce the energy barrier of the transition from interatomic disordering to ordering, and to resist interparticulate sintering via strong M-O-C bonding. This synthesis results in a nanosized core/shell structure featuring an interatomically ordered PtM core and a Pt shell of two to three atomic layers in thickness and can be extended to the multicomponent PtM (M = Co, FeCo, FeCoNi, FeCoNiGa) systems. The electron enrichment in the Pt outer shell induced by the compressive strain leads to the enhanced antibonding orbital occupation below the Fermi level and accelerated OH* desorption kinetics. The optimized PtCo-O/C-6 catalyst presents excellent ORR activity (mass activity = 1.28 A mgPt-1 at 0.9 ViR-free, peak power densities = 2.38/1.25 W cm-2 in H2-O2/-air) and durability (∼1% activity loss in over 50 h in air condition) in fuel cells at a total Pt loading of 0.1 mgPt cm-2. Furthermore, we establish a systematic correlation to elucidate the formation mechanisms of highly ordered intermetallic catalysts underlying oxygen vacancies. This study provides a general approach for the large-scale production of highly ordered and nanosized Pt-dispersed intermetallic catalysts.

Piezoelectric-Enhanced Nanocatalysts Trigger Neutrophil N1 Polarization against Bacterial Biofilm by Disrupting Redox Homeostasis.

Strategies of manipulating redox signaling molecules to inhibit or activate immune signals have revolutionized therapeutics involving reactive oxygen species (ROS). However, certain diseases with dual resistance barriers to the attacks by both ROS and immune cells, such as bacterial biofilm infections of medical implants, are difficult to eradicate by a single exogenous oxidative stimulus due to the diversity and complexity of the redox species involved. Here, this work demonstrates that metal-organic framework (MOF) nanoparticles capable of disrupting the bacterial ROS-defense system can dismantle bacterial redox resistance and induce potent antimicrobial immune responses in a mouse model of surgical implant infection by simultaneously modulating redox homeostasis and initiating neutrophil N1 polarization in the infection microenvironment. Mechanistically, the piezoelectrically enhanced MOF triggers ROS production by tilting the band structure and acts synergistically with the aurintricarboxylic acid loaded within the MOF, which inhibits the activity of the cystathionine γ-cleaving enzyme. This leads to biofilm structure disruption and antigen exposure through homeostatic imbalance and synergistic activation of neutrophil N1 polarization signals. Thus, this study provides an alternative but promising strategy for the treatment of antibiotic-resistant biofilm infections.

High Fe-Loading Single-Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy.

The current single-atom catalysts (SACs) for medicine still suffer from the limited active site density. Here, we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron. The constructed iron SACs (h3-FNC) with a high metal loading of 6.27 wt% and an optimized adjacent Fe distance of ~ 4 Å exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects. Attractively, a "density effect" has been found at a high-enough metal doping amount, at which individual active sites become close enough to interact with each other and alter the electronic structure, resulting in significantly boosted intrinsic activity of single-atomic iron sites in h3-FNCs by 2.3 times compared to low- and medium-loading SACs. Consequently, the overall catalytic activity of h3-FNC is highly improved, with mass activity and metal mass-specific activity that are, respectively, 66 and 315 times higher than those of commercial Pt/C. In addition, h3-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion (O2·-) and glutathione (GSH) depletion. Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h3-FNCs in promoting wound healing. This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

Single-Atom Catalysts with Isolated Cu1-N4 Sites for Atopic Dermatitis Cascade Catalytic Therapy via Activating PPAR Signaling.

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu1-N4 sites anchored on carbon support (Cu1-N4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu1-N4 ISACs enable the sequential conversion of O2•- to H2O2 and then to harmless H2O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu1-N4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu1-N4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.

Ultrasound-triggered and glycosylation inhibition-enhanced tumor piezocatalytic immunotherapy.

Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system to attack tumor cells. However, a high level of N-glycosylation can protect tumor cells, compromising the anticancer immunity of nanocatalytic immunotherapy. Here, we show a 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold for enhanced cancer piezocatalytic immunotherapy. After the implantation in the tumor, DBG generates both reactive oxygen species (ROS) and piezoelectric signals when excited with ultrasound irradiation, significantly promoting the activation of anticancer immunity. Meanwhile, 2-DG released from ROS-sensitive DBG disrupts the N-glycans synthesis, further overcoming the immunosuppressive microenvironment of tumors. The synergy effects of ultrasound-triggered and glycosylation inhibition enhanced tumor piezocatalytic immunotherapy are demonstrated on four mouse cancer models. A "hot" tumor-immunity niche is produced to inhibit tumor progress and lung metastasis and elicit strong immune memory effects. This work provides a promising piezocatalytic immunotherapy for malignant solid tumors featuring both low immunogenicity and high levels of N-glycosylation.

Nebulized Immunotherapy of Orthotopic Lung Cancer by Mild Magnetothermal-based Innate Immunity Activations.

Advances in adaptive immunity have greatly contributed to the development of cancer immunotherapy. However, its over-low efficacy and insufficient invasion of immune cells in the tumor tissue, and safety problems caused by cytokine storm, have seriously impeded further clinical application for solid tumor immunotherapy. Notably, the immune microenvironment of the lungs is naturally enriched with alveolar macrophages (AMs). Herein, we introduce a novel nebulized magnetothermal immunotherapy strategy to treat orthotopic lung cancer by using magnetothermal nanomaterial (Zn-CoFe2O4@Zn-MnFe2O4-PEG, named ZCMP), which can release iron ions via an acid/thermal-catalytic reaction to maximize the use of lung's immune environment through the cascade activations of AMs and natural killer (NK) cells. Nebulized administration greatly enhance drug bioavailability by localized drug accumulation at the lesion site. Upon mild magnetic hyperthermia, the released iron ions catalyze endogenous H2O2 decomposition to produce reactive oxygen species (ROS), which triggers the M1 polarization of AMs, and the resultant inflammatory cytokine IFN-ß, IL-1ß and IL-15 releases to activate c-Jun, STAT5 and GZMB related signaling pathways, promoting NK cells proliferation and activation. This innovative strategy optimally utilizes the lung's immune environment and shows excellent immunotherapeutic outcomes against orthotopic lung cancer.

Triple Regulations via Fe Redox Boosting Nitrate Reduction to Ammonia at Industrial Current Densities.

Electrochemical nitrate reduction reaction (NO3-RR) has promising prospects for green synthesis of ammonia and environmental remediation. However, the performance of catalysts at high current density usually suffers from the high energy barrier for the nitrate (NO3-) to nitrite (NO2-) and the competitive hydrogen evolution. Herein, we proposed a two-step relay mechanism through spontaneous redox reaction followed electrochemical reaction by introducing low-valence Fe species into Ni2P nanosheets to significantly enhance the NO3-RR performance at industrial current density. The existence of low-valence Fe species bypasses the NO3- to NO2- step through the spontaneous redox with NO3- to produce NO2- and Fe2O3, regulates the electronic structure of Ni2P to reduce the barrier of NO2- to NH3, thirdly prohibits the hydrogen evolution by consuming the excess active hydrogen through reduction of Fe2O3 to recover low-valence Fe species. The triple regulations via Fe redox during the two-step relay reactions guarantee the Fe-Ni2P@NF high ammonia yield of 120.1 mg h-1 cm-2 with Faraday efficiency of more than 90% over a wide potential window and a long-term stability of more than 130 h at ~1000 mA cm-2. This work provides a new strategy to realize the design and synthesis of nitrate reduction electrocatalysts at high current densities.

A MOF@MOF S-scheme Heterojunction with Lewis Acid-Base Sites Synergistically Boosts Cocatalyst-Free CO2 Cycloaddition.

The photocatalytic cycloaddition reaction between CO2 and epoxide is one of the most promising green routes for CO2 utilization, for which high performance photocatalysts are intensely desired. Herein, we have constructed an S-scheme heterojunction of MIL-125@ZIF-67 modified by amino groups, which achieves a cyclic carbonate yield of as high as 99 % without employing any co-catalyst, outperforming the previously reported photocatalysts. In-situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and in-situ electron paramagnetic resonance (EPR) spectroscopy reveal the important role of photogenerated electron migration from Lewis acid (Co) sites to the O atom of epoxide in triggering its ring-opening (the rate-determining step of CO2 cycloaddition reaction) under the assistance of photogenerated hole. Synergistically and concurrently, the Lewis base (amino groups) sites activate CO2 to CO2*, facilitating the following CO2 cycloaddition. Such a synergistic effect provides a most favorable approach to design efficient heterogeneous photocatalysts with dual/multiple-active sites for CO2 cycloaddition reaction.

Magnetothermal-activated gene editing strategy for enhanced tumor cell apoptosis.

Precise and effective initiation of the apoptotic mechanism in tumor cells is one of the most promising approaches for the treatment of solid tumors. However, current techniques such as high-temperature ablation or gene editing suffer from the risk of damage to adjacent normal tissues. This study proposes a magnetothermal-induced CRISPR-Cas9 gene editing system for the targeted knockout of HSP70 and BCL2 genes, thereby enhancing tumor cell apoptosis. The magnetothermal nanoparticulate platform is composed of superparamagnetic ZnCoFe2O4@ZnMnFe2O4 nanoparticles and the modified polyethyleneimine (PEI) and hyaluronic acid (HA) on the surface, on which plasmid DNA can be effectively loaded. Under the induction of a controllable alternating magnetic field, the mild magnetothermal effect (42℃) not only triggers dual-genome editing to disrupt the apoptosis resistance mechanism of tumor cells but also sensitizes tumor cells to apoptosis through the heat effect itself, achieving a synergistic therapeutic effect. This strategy can precisely regulate the activation of the CRISPR-Cas9 system for tumor cell apoptosis without inducing significant damage to healthy tissues, thus providing a new avenue for cancer treatment.

Construction of an electron-transfer channel via Cu-O-Ni to inhibit the overoxidation of Ni for durable methanol oxidation at industrial current density.

The electrocatalytic methanol oxidation reaction (MOR) is a viable approach for realizing high value-added formate transformation from biomass byproducts. However, usually it is restricted by the excess adsorption of intermediates (COad) and overoxidation of catalysts, which results in low product selectivity and inactivation of the active sites. Herein, a novel Cu-O-Ni electron-transfer channel was constructed by loading NiCuO x on nickel foam (NF) to inhibit the overoxidation of Ni and enhance the formate selectivity of the MOR. The optimized NiCuO x -2/NF demonstrated excellent MOR catalytic performance at industrial current density (E 500 = 1.42 V) and high faradaic efficiency of ∼100%, as well as durable formate generation up to 600 h at ∼500 mA cm-2. The directional electron transfer from Cu to Ni and enhanced lattice stability could alleviate the overoxidation of Ni(iii) active sites to guarantee reversible Ni(ii)/Ni(iii) cycles and endow NiCuO x -2/NF with high stability under increased current density, respectively. An established electrolytic cell created by coupling the MOR with the hydrogen evolution reaction could produce H2 with low electric consumption (230 mV lower voltage at 400 mA cm-2) and concurrently generated the high value-added product of formate at the anode.

Membrane-Free Electrocatalytic Co-Conversions of PBS Waste Plastics and Maleic Acid into High-Purity Succinic Acid Solid.

Plastic pollution, an increasingly serious global problem, can be addressed through the full lifecycle management of plastics, including plastics recycling as one of the most promising approaches. System design, catalyst development, and product separation are the keys in improving the economics of electrocatalytic plastics recycling. Here, a membrane-free co-production system was devised to produce succinic acid (SA) at both anode and cathode respectively by the co-electrolysis of polybutylene succinate (PBS) waste plastics and biomass-derived maleic acid (MA) for the first time. To this end, Cr3+-Ni(OH)2 electrocatalyst featuring much enhanced 1,4-butanediol (BDO) oxidation reaction (BOR) activity has been synthesized and the role of doped Cr has been revealed as an "electron puller" to accelerate the rate-determining step (RDS) in the Ni2+/Ni3+ cycling. Impressively, an extra-high SA production rate of 3.02 g h-1 and ultra-high apparent Faraday efficiency towards SA (FEapparent=181.5 %) have been obtained. A carbon dioxide-assisted sequential precipitation approach has been developed to produce high-purity SA and byproduct NaHCO3 solids. Preliminary techno-economic analysis demonstrates that the reported system is economically profitable and promising for future industrial applications.

Allicin‒Decorated FeO1-xOH Nanocatalytic Medicine for Fe2+/Fe3+ Cycling‒Promoted Efficient and Sustained Tumor Regression.

In the tumor treatment by Fenton reaction‒based nanocatalytic medicines, the gradual consumption of Fe(II) ions greatly reduces the production of hydroxyl radicals, one of the most active reactive oxygen species (ROS), leading to much deteriorated therapeutic efficacy. Meanwhile, the ROS consumption caused by the highly expressed reduced glutathione (GSH) in the tumor microenvironment further prevents tumor apoptosis. Therefore, using the highly expressed GSH in tumor tissue to promote the Fe(III) reduction to Fe(II) can not only weaken the resistance of tumor to ROS attack, but also generate enough Fe(II) to accelerate the Fenton reaction. In view of this, an allicin‒modified FeO1-xOH nanocatalyst possessing varied valence states (II, III) has been designed and synthesized. The coexistence of Fe(II)/Fe(III) enables the simultaneous occurrence of Fenton reaction and GSH oxidation, and the Fe(III) reduction by GSH oxidation results in the promoted cyclic conversion of Fe ions in tumor and positive catalytic therapeutic effects. Moreover, allicin capable of regulating cell cycle and suppressing tumor growth is loaded on FeO1-xOH nanosheets to activate immune response against tumors and inhibit tumor recurrence, finally achieving the tumor regression efficiently and sustainably. This therapeutic strategy provides an innovative approach to formulate efficient antitumor nanomedicine for enhanced tumor treatment.

Anode-Electrolyte Interfacial Acidity Regulation Enhances Electrocatalytic Performances of Alcohol Oxidations.

The local acidity at the anode surface during electrolysis is apparently stronger than that in bulk electrolyte due to the deprotonation from the reactant, which leads to the deteriorated electrocatalytic performances and product distributions. Here, an anode-electrolyte interfacial acidity regulation strategy has been proposed to inhibit local acidification at the surface of anode and enhance the electrocatalytic activity and selectivity of anodic reactions. As a proof of the concept, CeO2-x Lewis acid component has been employed as a supporter to load Au nanoparticles to accelerate the diffusion and enrichment of OH- toward the anode surface, so as to accelerate the electrocatalytic alcohol oxidation reaction. As the result, Au/CeO2-x exhibits much enhanced lactic acid selectivity of 81 % and electrochemical activity of 693 mA⋅cm-2 current density in glycerol oxidation reaction compared to pure Au. Mechanism investigation reveals that the introduced Lewis acid promotes the mass transport and concentration of OH- on the anode surface, thus promoting the generation of lactic acid through the simultaneous enhancements of Faradaic and non-Faradaic processes. Attractively, the proposed strategy can be used for the electro-oxidation performance enhancements of a variety of alcohols, which thereby provides a new perspective for efficient alcohol electro-oxidations and the corresponding electrocatalyst design.

Biomimetic-Structured Cobalt Nanocatalyst Suppresses Aortic Dissection Progression by Catalytic Antioxidation.

As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.

Electrocatalytic ORR-coupled ammoximation for efficient oxime synthesis.

State-of-the-art technology for cyclohexanone oxime production typically demands elevated temperature and pressure, along with the utilization of expensive hydroxylamine sulfate or oxidants. Here, we propose an electrochemistry-assisted cascade strategy for the efficient cyclohexanone ammoximation under ambient conditions by using in situ cathode-generated green oxidants of reactive oxygen species (ROS) such as OOH* and H2O2. This electrochemical reaction can take place at the cathode, achieving over 95% yield, 99% selectivity of cyclohexanone oxime, and an electron-to-oxime (ETO) efficiency of 96%. Mechanistic analysis reveals that, in addition to the direct ammoximation by in situ-generated OOH* by electrocatalytic ORR, Ti-MOR also play a major role in capturing OOH* directly and converting the in situ-generated H2O2 to OOH*, thus accelerating the ORR-coupled cascade production of cyclohexanone oxime. This work paves a mild, economical, and sustainable energy-efficient electrocatalytic route for the oxime production using oxygen, ammonium bicarbonate, and cyclohexanone.

Electrocatalytic functional group conversion-based carbon resource upgrading.

The conversions of carbon resources, such as alcohols, aldehydes/ketones, and ethers, have been being one of the hottest topics most recently for the goal of carbon neutralization. The emerging electrocatalytic upgrading has been regarded as a promising strategy aiming to convert carbon resources into value-added chemicals. Although exciting progress has been made and reviewed recently in this area by mostly focusing on the explorations of valuable anodic oxidation or cathodic reduction reactions individually, however, the reaction rules of these reactions are still missing, and how to purposely find or rationally design novel but efficient reactions in batches is still challenging. The properties and transformations of key functional groups in substrate molecules play critically important roles in carbon resources conversion reactions, which have been paid more attention to and may offer hidden keys to achieve the above goal. In this review, the properties of functional groups are addressed and discussed in detail, and the reported electrocatalytic upgrading reactions are summarized in four categories based on the types of functional groups of carbon resources. Possible reaction pathways closely related to functional groups will be summarized from the aspects of activation, cleavage and formation of chemical bonds. The current challenges and future opportunities of electrocatalytic upgrading of carbon resources are discussed at the end of this review.

An explainable long short-term memory network for surgical site infection identification.

BACKGROUND: Currently, surgical site infection surveillance relies on labor-intensive manual chart review. Recently suggested solutions involve machine learning to identify surgical site infections directly from the medical record. Deep learning is a form of machine learning that has historically performed better than traditional methods while being harder to interpret. We propose a deep learning model, a long short-term memory network, for the identification of surgical site infection from the medical record with an attention layer for explainability. METHODS: We retrieved structured data and clinical notes from the University of Utah Health System's electronic health care record for operative events randomly selected for manual chart review from January 2016 to June 2021. Surgical site infection occurring within 30 days of surgery was determined according to the National Surgical Quality Improvement Program definition. We trained the long short-term memory model along with traditional machine learning models for comparison. We calculated several performance metrics from a holdout test set and performed additional analyses to understand the performance of the long short-term memory, including an explainability analysis. RESULTS: Surgical site infection was present in 4.7% of the total 9,185 operative events. The area under the receiver operating characteristic curve and sensitivity of the long short-term memory was higher (area under the receiver operating characteristic curve: 0.954, sensitivity: 0.920) compared to the top traditional model (area under the receiver operating characteristic curve: 0.937, sensitivity: 0.736). The top 5 features of the long short-term memory included 2 procedure codes and 3 laboratory values. CONCLUSION: Surgical site infection surveillance is vital for the reduction of surgical site infection rates. Our explainable long short-term memory achieved a comparable area under the receiver operating characteristic curve and greater sensitivity when compared to traditional machine learning methods. With explainable deep learning, automated surgical site infection surveillance could replace burdensome manual chart review processes.

Pd/NiMoO4/NF electrocatalysts for the efficient and ultra-stable synthesis and electrolyte-assisted extraction of glycolate.

Electrocatalytic conversion of organic small molecules is a promising technique for value-added chemical productions but suffers from high precious metal consumption, poor stability of electrocatalysts and tedious product separation. Here, a Pd/NiMoO4/NF electrocatalyst with much lowered Pd loading amount (3.5 wt.%) has been developed for efficient, economic, and ultra-stable glycolate synthesis, which shows high Faradaic efficiency (98.9%), yield (98.8%), and ultrahigh stability (1500 h) towards electrocatalytic ethylene glycol oxidation. Moreover, the obtained glycolic acid has been converted to value-added sodium glycolate by in-situ acid-base reaction in the NaOH electrolyte, which is atomic efficient and needs no additional acid addition for product separation. Moreover, the weak adsorption of sodium glycolate on the catalyst surface plays a significant role in avoiding excessive oxidation and achieving high selectivity. This work may provide instructions for the electrocatalyst design as well as product separation for the electrocatalytic conversions of alcohols.

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy.

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.