Tailoring atomically local electric field of NiFe layered double hydroxides with Ag dopants to boost oxygen evolution kinetics.

The demand for clean energy sources has driven focus towards advanced electrochemical systems. However, the sluggish kinetics of the oxygen evolution reaction (OER) constrain the energy conversion efficiency of relevant devices. Herein, a one-step method is reported to grow oxygen vacancies (Vo) rich NiFeAg layered double hydroxides nanoclusters on carbon cloth (Vo-NiFeAg-LDH/CC) for serving as the self-supporting electrode to catalyze OER. The OER performance of Vo-NiFeAg-LDH/CC has been remarkably enhanced through Ag and Vo co-modification compared with pristine NiFe-LDH, achieving a low Tafel slope of 49.7 mV dec-1 in 1 m KOH solution. Additionally, the current density of Vo-NiFeAg-LDH/CC is 3.23 times higher than that of the state-of-art IrO2 at 2 V under an alkaline flow electrolyzer setup. Theoretical calculations and experimental results collectively demonstrate that Ag dopant and Vo strengthen the O* adsorption with active sites, further promoting the deprotonation step from OH* to O* and accelerating the catalytic reaction. In a word, this work clarifies the structural correlation and synergistic mechanism of Ag dopant and Vo, providing valuable insights for the rational design of catalyst for renewable energy applications.

Effectiveness of repeated low-level red light in myopia prevention and myopia control.

BACKGROUND/AIMS: To compare the effects of repeated low-level red light (RLRL) treatment on axial length growth and refractive error changes in myopic and premyopic children. METHODS: Subjects were assigned randomly to four subgroups: myopia-RLRL group (M-RL), myopia-control group (M-C), premyopia-RLRL group (PM-RL) and premyopia-control group (PM-C). Subjects in the RLRL group completed a 12-month treatment composed of a 3 min RLRL treatment session twice daily, with an interval of at least 4 hours, for 7 days per week. Visits were scheduled before and at 1-month, 3-month, 6-month, 9-month and 12-month follow-up after the treatment. Repeated-measures analysis of variance was used to compare the spherical equivalent refractive errors (SE) and axial length (AL) changes between the groups across the treatment period. RESULTS: After 12 months of treatment, in the myopia group, SE and AL changes were -0.078±0.375 D and 0.033±0.123 mm for M-RL and -0.861±0.556 D and 0.415±0.171 mm for M-C; in the premyopia group, the progression of SE and AL was -0.181±0.417 D and 0.145±0.175 mm for PM-RL and -0.521±0.436 D and 0.292±0.128 mm for PM-C. PM-RL indicated a lower myopia incidence than PM-C (2.5% vs 19.4%). Additionally, the percentage of AL shortening in the M-RL was higher than that in the PM-RL before the 9-month follow-up. CONCLUSION: RLRL effectively delayed myopia progression in children with myopia and reduced the incidence of myopia in premyopic children. Moreover, RLRL exhibited a stronger impact on myopic children compared with premyopic individuals.

Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis.

Mesenchymal stem cells (MSCs) experience substantial viability issues in the stroke infarct region, limiting their therapeutic efficacy and clinical translation. High levels of deadly reactive oxygen radicals (ROS) and proinflammatory cytokines (PC) in the infarct milieu kill transplanted MSCs, whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs' viability. Based on the intrinsic hormesis effects in cellular biology, we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy. This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer. In this system, extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation. Meanwhile, the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing. The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days. This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

In-Situ Spontaneous Electropolymerization Enables Robust Hydrogel Electrolyte Interfaces in Aqueous Batteries.

Hydrogels hold great promise as electrolytes for emerging aqueous batteries, for which establishing a robust electrode-hydrogel interface is crucial for mitigating side reactions. Conventional hydrogel electrolytes fabricated by ex situ polymerization through either thermal stimulation or photo exposure cannot ensure complete interfacial contact with electrodes. Herein, we introduce an in situ electropolymerization approach for constructing hydrogel electrolytes. The hydrogel is spontaneously generated during the initial cycling of the battery, eliminating the need of additional initiators for polymerization. The involvement of electrodes during the hydrogel synthesis yields well-bonded and deep infiltrated electrode-electrolyte interfaces. As a case study, we attest that, the in situ-formed polyanionic hydrogel in Zn-MnO2 battery substantially improves the stability and kinetics of both Zn anode and porous MnO2 cathode owing to the robust interfaces. This research provides insight to the function of hydrogel electrolyte interfaces and constitutes a critical advancement in designing highly durable aqueous batteries.

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy.

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

Surface-tethered ROS-responsive micelle backpacks for boosting mesenchymal stem cell vitality and modulating inflammation in ischemic stroke treatment.

Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.

Nitrogen-doped porous carbon encapsulates multivalent cobalt-nickel as oxygen reduction reaction catalyst for zinc-air battery.

In this study, we present a bimetallic ion coexistence encapsulation strategy employing hexadecyl trimethyl ammonium bromide (CTAB) as a mediator to anchor cobalt-nickel (CoNi) bimetals in nitrogen-doped porous carbon cubic nanoboxes (CoNi@NC). The fully encapsulated and uniformly dispersed CoNi nanoparticles with the improved density of active sites help to accelerate the oxygen reduction reaction (ORR) kinetics and provide an efficient charge/mass transport environment. Zinc-air battery (ZAB) equipped CoNi@NC as cathode exhibits an open-circuit voltage of 1.45 V, a specific capacity of 870.0 mAh g-1, and a power density of 168.8 mW cm-2. Moreover, the two CoNi@NC-based ZABs in series display a stable discharge specific capacity of 783.0 mAh g-1, as well as a large peak power density of 387.9 mW cm-2. This work provides an effective way to tune the dispersion of nanoparticles to boost active sites in nitrogen-doped carbon structure, and enhance the ORR activity of bimetallic catalysts.

Cooperation between Dual Metal Atoms and Nanoclusters Enhances Activity and Stability for Oxygen Reduction and Evolution.

We have achieved the synthesis of dual-metal single atoms and atomic clusters that co-anchor on a highly graphitic carbon support. The catalyst comprises Ni4 (and Fe4) nanoclusters located adjacent to the corresponding NiN4 (and FeN4) single-atom sites, which is verified by systematic X-ray absorption characterization and density functional theory calculations. A distinct cooperation between Fe4 (Ni4) nanoclusters and the corresponding FeN4 (NiN4) atomic sites optimizes the adsorption energy of reaction intermediates and reduces the energy barrier of the potential-determining steps. This catalyst exhibits enhanced oxygen reduction and evolution activity and long-cycle stability compared to counterparts without nanoclusters and commercial Pt/C. The fabricated Zn-air batteries deliver a high power density and long-term cyclability, demonstrating their prospects in energy storage device applications.

Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke.

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

Oxidation State Engineering in Octahedral Ni by Anchored Sulfate to Boost Intrinsic Oxygen Evolution Activity.

Promoting the electron occupancy of active sites to unity is an effective method to enhance the oxygen evolution reaction (OER) performance of spinel oxides, but it remains a great challenge. Here, an in situ approach is developed to modify the valence state of octahedral Ni cations in NiFe2O4 inverse spinel via surface sulfates (SO42-). Different from previous studies, SO42- is directly anchored on the spinel surface instead of forming from uncontrolled conversion or surface reconstruction. Experiment and theoretical calculations reveal the precise adsorption sites and spatial arrangement for SO42- species. As a main promoting factor, surface SO42- effectively converts the crystal field stable Ni state (t2g6eg2) to the near-unity eg electron state (t2g6eg1). Moreover, the inevitable oxygen vacancies (Vo) further optimize the energy barrier of the potential-determining step (from OH* to O*). This co-modification strategy enhances turnover frequency-based electrocatalytic activity about two orders higher than the control sample without surface sulfates. This work may provide insight into the OER activity enhancement mechanism by the oxyanion groups.

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma.

The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.

Doughty-electronegative heteroatom-induced defective MoS2 for the hydrogen evolution reaction.

Producing hydrogen through water electrolysis is one of the most promising green energy storage and conversion technologies for the long-term development of energy-related hydrogen technologies. MoS2 is a very promising electrocatalyst which may replace precious metal catalysts for the hydrogen evolution reaction (HER). In this work, doughty-electronegative heteroatom defects (halogen atoms such as chlorine, fluorine, and nitrogen) were successfully introduced in MoS2 by using a large-scale, green, and simple ball milling strategy to alter its electronic structure. The physicochemical properties (morphology, crystallization, chemical composition, and electronic structure) of the doughty-electronegative heteroatom-induced defective MoS2 (N/Cl-MoS2) were identified using SEM, TEM, Raman, XRD, and XPS. Furthermore, compared with bulk pristine MoS2, the HER activity of N/Cl-MoS2 significantly increased from 442 mV to 280 mV at a current of 10 mA cm-2. Ball milling not only effectively reduced the size of the catalyst material, but also exposed more active sites. More importantly, the introduced doughty-electronegative heteroatom optimized the electronic structure of the catalyst. Therefore, the doughty-electronegative heteroatom induced by mechanical ball milling provides a useful reference for the large-scale production of green, efficient, and low-cost catalyst materials.

Heterogeneous Ni3P/Ni nanoparticles with optimized Ni active sites anchored in N-doped mesoporous nanofibers for boosting pH-universal hydrogen evolution.

Developing low-cost, environmentally friendly and efficient non-precious metal electrocatalysts as alternatives to noble metals for the hydrogen evolution reaction (HER) is highly essential for the sustainable advancement of green hydrogen energy. Herein, a novel heterostructured Ni3P/Ni nanoparticle anchored in nitrogen-doped mesoporous carbon nanofibers (Ni3P/Ni@N-CNFs) is prepared by a facile solid-phase calcination protocol. The results demonstrated that benefiting from the intensive electronic coupling effect at the interface of the Ni3P/Ni heterostructure, the electron configuration of the Ni active site is optimized and thus the favorable HER activity. Furthermore, the N-doped carbon nanofiber scaffold with an extensive mesoporous structure endows Ni3P/Ni@N-CNFs with abundant electrochemically active sites together with excellent conductivity and stability, contributing to fast electron/mass transport. As expected, the resultant Ni3P/Ni@N-CNF electrocatalyst exhibited exceptional HER catalytic properties under universal pH conditions, driving a current density of 10 mA cm-2 at pretty low overpotentials of 121 mV, 145 mV and 187 mV in acidic, basic and neutral solutions, respectively, and retaining the catalytic stability for over 60 h. This intriguing work represents a fresh perspective for designing and exploiting highly advanced phosphide electrocatalysts for green hydrogen fuel production.

Vitality-Enhanced Dual-Modal Tracking System Reveals the Dynamic Fate of Mesenchymal Stem Cells for Stroke Therapy.

Mesenchymal stem cell (MSC) therapy via intravenous transplantation exhibits great potential for brain tissue regeneration, but still faces thorny clinical translation challenges as the unknown dynamic fate leads to the contentious therapeutic mechanism and the poor MSC viability in harsh lesions limits therapeutic efficiency. Here, a vitality-enhanced dual-modal tracking system is designed to improve engraftment efficiency and is utilized to noninvasively explore the fate of intravenous transplanted human umbilical cord-derived MSCs during long-term treatment of ischemic stroke. Such a system is obtained by bioorthogonally conjugating magnetic resonance imaging (MRI) contrast and near-infrared fluorescence (NIRF) imaging nanoparticles to metabolic glycoengineered MSCs with a lipoic acid-containing extracellular antioxidative protective layer. The dynamic fates of MSCs in multi-dimensional space-time evolution are digitally detailed for up to 28 days using MRI and NIRF imaging equipment, and the protective layer greatly shields MSCs from reactive oxygen spices (ROS) degradation, enhances MSC survival, and engraftment efficiency. Additionally, it is observed that the bioengineered MSCs exhibit dynamic intelligent responses corresponding to microenvironment remodeling and exert enhanced therapeutic effects. This dual-modal tracking system enables long-term tracking of MSCs while improving their viability at the lesion sites, which may serve as a valuable tool for expediting the clinical translation of MSC therapy.

Metformin and histone deacetylase inhibitor based anti-inflammatory nanoplatform for epithelial-mesenchymal transition suppression and metastatic tumor treatment.

Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy.

Neutrophil-Biomimetic "Nanobuffer" for Remodeling the Microenvironment in the Infarct Core and Protecting Neurons in the Penumbra via Neutralization of Detrimental Factors to Treat Ischemic Stroke.

High level of detrimental factors including reactive oxygen species (ROS) and inflammatory cytokines accumulated in the infarct core and their erosion to salvageable penumbra are key pathological cascades of ischemia-reperfusion injury in stroke. Few neuroprotectants can remodel the hostile microenvironment of the infarct core for the failure to interfere with dead or biofunctionally inactive dying cells. Even ischemia-reperfusion injury is temporarily attenuated in the penumbra by medications; insults of detrimental factors from the core still erode the penumbra continuously along with drug metabolism and clearance. Herein, a strategy named "nanobuffer" is proposed to neutralize detrimental factors and buffer destructive erosion to the penumbra. Inspired by neutrophils' tropism to the infarct core and affinity to inflammatory cytokines, poly(lactic-co-glycolic acid) (PLGA) nanoparticles are coated with neutrophil membrane to target the infarct core and absorb inflammatory cytokines; α-lipoic acid is decorated on the surface and cannabidiol is loaded for ROS scavenging and neuroprotection, respectively, to construct the basic unit of the nanobuffer. Such a nanobuffer exerts a comprehensive effect on the infarct area via detrimental factor neutralization and cannabidiol-induced neuroprotection. Besides, the nanobuffer can possibly be enhanced by dynamic ROP (ring-opening-polymerization)-induced membrane cross-fusion among closely adjacent units in vivo. Systematic evaluations show significant decrease of detrimental factors in the core and the penumbra, reduced infarct volume, and improved neurological recovery compared to the untreated group of stroke rats.

Biaxially Strained MoS2 Nanoshells with Controllable Layers Boost Alkaline Hydrogen Evolution.

Strain in layered transition-metal dichalcogenides (TMDs) is a type of effective approach to enhance the catalytic performance by activating their inert basal plane. However, compared with traditional uniaxial strain, the influence of biaxial strain and the TMD layer number on the local electronic configuration remains unexplored. Herein, via a new in situ self-vulcanization strategy, biaxially strained MoS2 nanoshells in the form of a single-crystalline Ni3 S2 @MoS2 core-shell heterostructure are realized, where the MoS2 layer is precisely controlled between the 1 and 5 layers. In particular, an electrode with the bilayer MoS2 nanoshells shows a remarkable hydrogen evolution reaction activity with a small overpotential of 78.1 mV at 10 mA cm-2 , and negligible activity degradation after durability testing. Density functional theory calculations reveal the contribution of the optimized biaxial strain together with the induced sulfur vacancies and identify the origin of superior catalytic sites in these biaxially strained MoS2 nanoshells. This work highlights the importance of the atomic-scale layer number and multiaxial strain in unlocking the potential of 2D TMD electrocatalysts.

Atomically Dispersed Co2 -N6 and Fe-N4 Costructures Boost Oxygen Reduction Reaction in Both Alkaline and Acidic Media.

Polynary transition-metal atom catalysts are promising to supersede platinum (Pt)-based catalysts for oxygen reduction reaction (ORR). Regulating the local configuration of atomic catalysts is the key to catalyst performance enhancement. Different from the previously reported single-atom or dual-atom configurations, a new type of ternary-atom catalyst, which consists of atomically dispersed, nitrogen-coordinated Co-Co dimers, and Fe single sites (i.e., Co2 -N6 and Fe-N4 structures) that are coanchored on highly graphitized carbon supports is developed. This unique atomic ORR catalyst outperforms the catalysts with only Co2 -N6 or Fe-N4 sites in both alkaline and acid conditions. Density functional theory calculations clearly unravels the synergistic effect of the Co2 -N6 and Fe-N4 sites, which can induce higher filling degree of Fe-d orbitals and favors the binding capability to *OH intermediates (the rate determining step). This ternary-atom catalyst may be a promising alternative to Pt to drive the cathodic ORR in zinc-air batteries.

Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of "micro-thrombi", and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.

Perovskite-Type Solid Solution Nano-Electrocatalysts Enable Simultaneously Enhanced Activity and Stability for Oxygen Evolution.

A trade-off between catalytic activity and structural stability generally exists in oxygen evolution electrocatalysis, especially in acidic environment. This dilemma limits the development of higher-performance electrocatalysts that are required by next-generation electrochemical technologies. Here it is demonstrated that the inverse catalytic activity-structural stability relation can be broken by alloying catalytically inert strontium zirconate with the other catalytically active perovskite, strontium iridate. This strategy results in an alloyed perovskite electrocatalyst with simultaneously improved iridium mass activity and structural stability, by about five times, for the oxygen evolution reaction under acidic conditions. The experimental and theoretical results suggest that the alloying strategy generates multiple positive effects, mainly including the reduction of catalyst size, the decrease of catalyst covalency, and the weakening of surface oxygen-binding ability. The synergistic optimization of bulk and surface properties, as a result, enhances the intrinsic activity and availability of surface iridium sites, whilst significantly inhibiting the surface cation corrosion during electrocatalysis.