Sepsis-associated encephalopathy (SAE) is a life-threatening neuroinflammatory complication of sepsis for which effective treatment remains unavailable. A major challenge is that most therapeutics cannot efficiently cross the blood-brain barrier or simultaneously address the coupled pathological processes driving disease progression, namely microglial pyroptosis and impaired neurotrophic support. Here, we report an ultrasound-gated nanobubble platform designed for SAE that enables sequential pyroptosis blockade and mechanotransduction-mediated neurorepair. The platform consists of sphingosine-1-phosphate-functionalized, disulfiram-loaded nanobubbles (S1P@DSF-NBs), which actively accumulate in inflamed cerebral vasculature via the S1P-S1PR1 axis and serve as a localized reservoir for ultrasound-programmed intervention. Under a dual-ultrasound regimen, low-intensity pulsed ultrasound first induces stable nanobubble oscillation, mechanically activating Piezo1-dependent CREB-BDNF signaling in microglia to restore neurotrophic support. Subsequent high-intensity pulsed ultrasound triggers nanobubble destabilization and localized disulfiram release, leading to gasdermin D inhibition, suppression of pyroptosis, and attenuation of inflammatory amplification. In a murine SAE model, ultrasound-programmed S1P@DSF-NBs reduced systemic and hippocampal inflammation, decreased neuronal loss by 40 %, and improved cognitive performance by 2.24-fold, while reprogramming microglia toward a neuroprotective phenotype and disrupting the pyroptotic inflammatory cascade. These findings demonstrate that ultrasound-programmed nanobubble therapy can concurrently interrupt inflammatory injury and restore neuroprotective signaling in SAE. This work establishes an actively targeted, ultrasound-responsive biomaterials strategy for ultrasound-programmed intervention in SAE and offers a versatile framework for the treatment of other neuroinflammatory disorders.

This article used a combination of polylactic acid (PLA) and short carbon fiber-reinforced polyamide-12 composite material (CFRP) and melt deposition molding technology to prepare hexagonal porous structural panels with different rotation angles. Adopting a combination of quasi-static compression experiments and finite element simulation analysis. Explored the effects of different concentrations of dichloromethane solvents, corrosion times, and configuration angles on the compressive properties of porous structural panels made of PLA and CFRP materials. The results indicated that as the corrosion time increased, the corrosion rate decreased, and the higher the corrosion concentration, the faster the corrosion rate. PLA specimens had a higher corrosion rate at a concentration of 30 %, while CFRP specimens had a concentration of 50 %. In terms of failure mode, PLA specimens exhibited local damage at low corrosion concentrations, while maintaining structural integrity but causing local instability at high corrosion concentrations. As the corrosion concentration increased, the double shear band became more prominent and the structure became stable in CFRP specimens. From a configuration perspective, the low concentration 0 degrees configuration performed well, while the high concentration PLA specimens were less affected by it than CFRP specimens. This study revealed the differences in corrosion behavior between PLA and CFRP, as well as the time-decay laws of the two materials; it proposed the "double shear band strengthening effect" of CFRP in corrosive environments, which held potential applications in the anti-corrosion design of composite materials.

Covalent organic frameworks (COFs) have emerged as the promising electrochemiluminescence (ECL) emitters due to their distinct advantages of diverse linkages and building blocks, designable molecular structures, and excellent chemical stability. However, efficient charge transfer within COFs is limited by the strong polarity of imine bonds. Herein, we synthesize a fully it-conjugated donor-acceptor (D-A) COF (Py-Bpda-COF) by integrating cyano-vinylene linkages with electron-rich pyrene (D) and electron-deficient bipyridine (A) units. The obtained Py-Bpda-COF demonstrates strong anodic ECL emission and excellent ECL stability. Experimental results and theoretical calculations reveal that the synergistic effect of the strong intramolecular charge separation driving force (D-A structure) and the extended sp2-carbon networks (vinylene linkages) significantly enhances charge separation efficiency and accelerates the intramolecular charge transfer between D and A moieties, thereby facilitating the ECL emission. As expected, Py-Bpda-COF can achieve high ECL efficiency (13.34 %), which is 17.79-fold and 3.74-fold higher than Py-PB-COF and Py-Bpy-COF, respectively. As a proof of concept, we demonstrate the construction of an ECL biosensor for sensitive detection of long non-coding RNA (lncRNA) with a detection limit of 86.52 fM. This research provides a new approach for the synthesis of COFs with high ECL efficiency and the construction of novel ECL biosensors.

Adeno-associated virus serotype 8 (AAV8) is a widely used gene therapy vector with the characteristics of high transduction efficiency and tissue specificity. Reliable detection of AAV8 is crucial for assessing therapeutic efficacy and tracking its in vivo distribution. Herein, we develop a nanobody-based electrochemiluminescence (ECL) imaging immunosensor based on integrating advanced functional materials with spatially resolved signal output for sensitive and visual detection of AAV8. This immunosensor employs a tetraphenylethylene-derived covalent organic framework (TC-COF) as the ECL emitter with the advantages of excellent chemical stability, structural rigidity, and aggregation-induced luminescence. Moreover, the gold-rhodium core-shell bimetallic nanoparticles (Au@Rh) are introduced as the efficient coreaction accelerators to promote the formation of triethylamine (TEA) radicals. Nanobodies serve as the high-affinity and low-steric-hindrance recognition elements with the advantages of enhanced epitope accessibility and stable surface immobilization. Both the Au@Rh and nanobodies contribute to good specificity and high sensitivity. Notably, this ECL immunosensor enables direct visualization of AAV8 binding events, and the pixel-based signal quantification ensures robust calibration and high reproducibility. This ECL immunosensor can achieve a wide linear detection range from 1 × 108 to 5 × 1011 vg/mL, with the limit of detection (LOD) reaching as low as 1 × 107.15 vg/mL. To the best of our knowledge, this work reports the first application of AAV8-specific nanobodies in an ECL biosensing platform. This study demonstrates a significant analytical advancement by integrating nanobody technology, COF-based luminescent materials, and catalytic nanoparticles into a robust and broadly applicable sensing platform for virus detection.

Electrochemiluminescence (ECL) has evolved into a powerful analytical technique due to its ultra-high sensitivity, low background noise, and precise electrochemical control. The development of efficient ECL emitters is central to advancing this technology for practical applications. Covalent organic frameworks (COFs) have recently emerged as promising candidates for constructing high-performance ECL systems. The tunable porosity, ordered π-conjugated structures, and versatile modular functionalities of COFs provide fast massive transport, effective electron transfer, rapid interfacial electrochemical reaction, and enhanced ECL emission performance. This review provides a comprehensive overview of the rational design strategies and structural engineering for COF-based ECL materials at the molecular level. Linkage chemistry, monomer selection (luminophores and π-conjugated non-ECL motifs), precise framework regulation, post-synthetic modification, composite formation, and other ECL enhancement strategies were discussed for developing COF-based ECL emitter. Both the incorporation of aggregation-induced emission and intramolecular charge transfer mechanisms are included to enhance ECL efficiency. Donor–acceptor conjugation, heteroatom element content, isomerism, substitution, and dimensional direction were regarded as effective strategies to regulate the electronic structure and band diagrams for designing high-performance ECL systems. The role of COFs as both active emitters and functional scaffolds for signal amplification is critically examined. Furthermore, their diverse analytical applications across biosensing, food safety, environmental monitoring, and chiral recognition are highlighted. By correlating structural features with ECL performance, this review offers insights into the design principles of next-generation reticular ECL materials and outlines future directions for their practical deployment in sensitive and selective sensing platforms.

The porphyrin-based hydrogen-bonded organic framework (HOF) offers a superior platform for decoding electrochemiluminescence (ECL) via controlling charge transfer due to its higher solubility, chemical stability, and tunable framework behavior. In this research, three kinds of HOFs including TDPP-HOF, TCPP-HOF, and TCNPP-HOF are synthesized based on a porphyrin tectonic plate decorated with 2,4-diaminotriazinyl (DAT), carboxyl, and nitrile moieties to study their ECL performances. The hydrazine as the coreactant can trigger TDPP-HOF at the low-excited positive potential to generate 15.8- and 112.9-fold enhancement in ECL signal than TCNPP-HOF and TCPP-HOF. Experimental results and density functional theory calculations verify that TDPP-HOF with a lower bandgap and a larger binding energy (ΔE) between coreactant and HOF is beneficial to intrareticular charge transfer (ICT), facilitating the enhancement of ECL performance. These results indicate that the peripheral substituents can establish a specialized outer-sphere microenvironment around the porphyrin center to tune both the HOF activity and the ECL performance. As a proof of concept, a simple TDPP-HOF-based ECL sensor is constructed to sensitively detect phenolic compounds. This research provides a new avenue for improving the ECL performance via modulating the outer-sphere microenvironment of HOFs.

Cuproptosis, a copper-dependent cell death, emerges as a potential anticancer strategy but still faces challenges of systemic toxicity from exogenous copper supplementation, tumor adaptation via glutathione (GSH)-mediated detoxification, and compensatory copper-efflux upregulation. These limitations impede mitochondrial respiratory dysfunction and proteotoxic stress that are essential for cuproptosis, highlighting the demand for tumor-specific copper metabolic modulation. Here, we engineer multifunctional nanoliposomes (DSF/S1P/ISDN-Lipos) that hijack endogenous copper transport for spatially controlled tumor-specific cuproptosis induction while enabling real-time therapeutic monitoring via gas enhanced ultrasonography. Modularly assembled from tumor-targeting sphingosine-1-phosphate (S1P), GSH-responsive nitric oxide (NO) prodrug isosorbide dinitrate (ISDN), and copper-chelator disulfiram (DSF), this DSF/S1P/ISDN-Lipos first facilitates blood-brain tumor barrier traversal and glioblastoma-specific accumulation. Then, intratumorally GSH converts DSF to dithiocarbamate (DTC), chelating endogenous copper into Cu(DTC)2 complexes on the liposome surface. Following internalization, coreleased Cu(DTC)2 and ISDN-derived NO deplete GSH while suppressing ATP7B efflux pumps, amplifying copper overload to trigger lipoylated protein aggregation and Fe-S cluster degradation. Notably, NO-generated ultrasound contrast enables spatiotemporal mapping of copper transport dynamics. In vivo, DSF/S1P/ISDN-Lipos demonstrated favorable biosafety and significantly suppressed orthotopic glioblastoma growth. This work presents a theranostic approach for metal homeostasis regulation, where gas therapy synergizes with endogenous metallo-reprogramming to overcome adaptive resistance.

Microcystin-LR (MC-LR) is an algae toxin that poses a serious threat to human health because of its multiorgan toxicity, genotoxicity, and carcinogenicity. Herein, we develop an electrochemiluminescent (ECL) immunosensor for MC-LR detection on the basis of aggregation-induced ECL (AIECL)-assisted self-enhancement strategy. The probe used in this assay is prepared by simultaneously encapsulating AIEgens (namely 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene (H4TCBPE) and its coreactant 2-(dibutylamino)ethanol (DBAE)) into silica to form ternary H4TCBPE@SiO2-DBAE nanoparticles. DBAE can function as a catalyzer to accelerate the in situ formation of SiO2 matrix and an intracoreactant to react with H4TCBPE for the generation of an intense ECL emission as a result of shortened electron transfer pathway and decreased energy loss. We further prepare a biocompatible and electroactive Ti3C2Tx/MoS2/Au hybrid that acts as the immuosensing substrate to accelerate interfacial electron transfer and conjugate the captured antibody (Ab1). Both Ab1-coated Ti3C2Tx/MoS2/Au and antibody (Ab2)-labeled H4TCBPE@SiO2-DBAE can interact with target MC-LR to obtain a sandwich immunosensor. This immunosensor enables quantitative detection of MC-LR antigen with a detection limit of 31 fg/mL and a broad linear range from 50 fg/mL to 10 ng/mL. The proposed strategy opens up a new avenue to fabricating new self-enhanced ECL emitters for sensitive monitoring of environmental microcystins.

Reducible metal-oxide based nanozymes have received much attention in recent years due to their excellent and tunable enzyme-mimicking properties. Herein, porous CeO2 nanorods supported Pt-based nanozymes with specific content of oxygen vacancy (Ov) were synthesized by combining atomic layer deposition and te following hydrogen activation strategy, among which the Pt/CeO2-650R nanozymes with average particle size of 1.6 nm exhibit the optimized peroxidase activity in the typical H2O2-TMB reaction systems, whose specific activity is 3-fold higher than that of Pt/CeO2 counterparts. Besides, the reduced nanozymes also present excellent degra-dation and antibiosis properties. The activity enhancement is ascribed to the Pt-Ov synergy contributing to the stronger capability to generate active radical species. This work affords new insights for in-depth understanding metal-Ov synergy in nanozyme catalysis field.

Constructing high-efficiency catalysts with high activity and selectivity is the long-term pursuit in heterogeneous catalysis field. Metal-oxygen vacancy (Ov) synergy provides a promising route to realizing the goal. In this study, the Pt/CoOx catalysts with Pt-Ov dual sites are designed by atomic layer deposition (ALD) for selective hydrogenation of cinnamaldehyde, and the Ov property, Pt size and the spatial relationship of Pt and CoOx can be well modulated. Experimental and theoretical investigations indicate that the substrate and hydrogen can be activated on Ov and Pt nanoparticles, respectively. The Ov introduced by ALD not only preferentially activates C=O bond of CALD to achieve high selectivity to CALA, but also enhances the ability to dissociate hydrogen on Pt nanoparticles through Pt-Ov electron transfer. Importantly, the optimized Pt40/CoOx-Ov catalysts with suitable Ov coordination and Pt sizes (2.5 nm) show lower adsorption energy for reactant molecules, obtaining significantly enhanced activity with a turnover frequency value of 202.5 mol(CALD).mol(Pt)(-1).min(-1) and obviously improved selectivity of desired products (93 %). This work offers a fundamental understanding of Pt-Ov synergy toward hydrogenation of unsaturated compounds.

Construction and optimization of stable atomically dispersed metal sites on SiO2 surfaces are important yet challenging topics. In this work, we developed the amino group-assisted atomic layer deposition strategy to deposit the atomically dispersed Pt on SiO2 support for the first time, in which the particle size and ratio of Pt entities from single atom (Pt1) to atomic cluster (Pt n ) and nanoparticle (Pt p ) on the SiO2 surface were well modulated. We demonstrated the importance of dual-site synergy for optimizing the activity of single-atom catalysts. The Pt1+n /SiO2-N catalysts with the coexistence of Pt1 and Pt n showed excellent activity and optimized selectivity (99% for haloanilines) in halonitrobenzenes hydrogenation, while Pt1/SiO2-N catalysts were almost inactive in the reaction. Mechanism investigation indicates that the Pt n site is beneficial for H2 dissociation, and the Pt1 site is energetically favorable for adsorption of the nitro group to complete the selective hydrogenation, which synergistically contributes to the optimized catalytic performances. This study provides a new strategy for constructing atomically dispersed metal species over the SiO2 support and demonstrates the significance of the synergy of dual active sites for enhancing the catalytic efficiency.

Integrating different reaction sites, such as single atom (SA), nanocluster (NC), and oxygen vacancy (Ov), in a specific photocatalyst affords a new prospect to break through the limitations of SA catalysis. However, the intrinsic influence mechanisms of cocatalyst size and Ov on the photocatalytic performance and synergy are still not well unraveled. Herein, we report the synthesis and investigation of atomically dispersed Pt-based photocatalysts surface-confined in Ov-containing porous TiO2 nanoflowers via atomic layer deposition. The SA-NC coexisting PtSA+NC@TiO2 photocatalysts exhibit optimized hydrogen evolution activity (2260 h(-1)), which is 3.6-fold higher than that of Pt-SA@TiO2 counterparts. Moreover, the activity can be further remarkably enhanced to 3645 h(-1) by engineering the cocatalyst size and Ov concentration. We identify the ad-/desorption sites of the reacting molecules and unravel the synergistic catalytic mechanisms of the active speciesthrough characterizations and density functional theory calculations: Pt NC is responsible for the adsorption-dissociation of H2O molecules preferentially adsorbed on Ti sites and meanwhile lowers the d-band center of Pt SA responsible for the desorption of H-2 molecules, and the adjacent Ov can stabilize the cocatalysts and modify the electronic energy distribution of Pt NC, achieving the optimized adsorption state toward the *OH intermediate. The present multiple-site engineering concept and mechanistic insights are expected to shed light on the rational design of atomically dispersed photocatalysts.

Nanozymes are nanomaterials with natural enzyme characteristics, which are expected to be potential substitutes of traditional enzymes. In this study, the 1Al/MIL-100(Fe) nanozymes with excellent peroxidase-like activity were synthesized by the ultrathin modification (one-cycle Al2O3) strategy of atomic layer deposition, whose peroxidase-like activity is almost doubled compared with MIL-100(Fe) nanozymes. Investigation of the catalytic mechanism indicates that the increased amount of hydroxyl radical is responsible for the much-enhanced peroxidase-like activity of 1Al/MIL-100(Fe) nanozymes. Furthermore, the catalytic effect of the designed nanozymes is inhibited by glutathione through consuming the oxidized 3,3',5,5'-tetramethylbenzidine in the reaction system. The 1Al/MIL-100(Fe) nanozymes also achieve the sensitive and selective detection of glutathione, which have an excellent linear response to glutathione concentration in the range 0.01-1000 mu M with a detection limit of 2.2 nM. The ultrathin modification strategy can be potentially extended to synthesize other high-efficiency nanozyme materials.

In this paper, polylactic acid materials combined with fused deposition molding technology were used to prepare porous structural panels. A combination of quasi-static compression experiment and finite element simulation analysis was adopted to explore effect of pitting time and concentration of dichloromethane solvent on the compression properties of porous structural panels. Results showed that surface of 100% solvent became smooth and flat, while surface of 80% solvent only formed a dense covering film. When specimens continues to suffer from corrosion, the single-layer specimens changed its deformation directions to a certain extent, while the instability of the two layers bolted porous structural panels gradually decreased when the corrosion damage increased. Mass concentration of 90% was the critical point for local mechanical performance of specimens.

Although metal single-atom (SA)-based nanomaterials are explored as sonosensitizers for sonodynamic therapy (SDT), they normally exhibit poor activities and need to combine with other therapeutic strategies. Herein, the deposition of metal SAs on oxygen vacancy (OV)-rich WO3- x nanosheets to generate a synergistic effect for efficient SDT is reported. Crystalline WO3 and OV-rich WO3- x nanosheets are first prepared by simple calcination of the WO3·H2O nanosheets under an air and N2 atmosphere, respectively. Pt, Cu, Fe, Co, and Ni metal SAs are then deposited on WO3- x nanosheets to obtain metal SA-decorated WO3- x nanocomposites (M-WO3- x). Importantly, the Cu-WO3- x sonosensitizer exhibits a much higher activity for ultrasound (US)-induced production of reactive oxygen species than that of the WO3- x and Cu SA-decorated WO3, which is also higher than other M-WO3- x nanosheets. Both the experimental and theoretical results suggest that the excellent SDT performance of the Cu-WO3- x nanosheets should be attributed to the synergistic effect between Cu SAs and WO3- x OVs. Therefore, after polyethylene glycol modification, the Cu-WO3- x can quickly kill cancer cells in vitro and effectively eradicate tumors in vivo under US irradiation. Transcriptome sequencing analysis and further molecular validation suggest that the Cu-WO3- x-mediated SDT-activated apoptosis and TNF signaling pathways are potential drivers of tumor apoptosis induction.

We present a dimensional regulating charge transfer strategy to achieve an enhanced electrochemiluminescence (ECL) by constructing a one-dimensional pyrene-based covalent organic framework (1D-COF). The dual-chain-like edge architecture in 1D-COF facilitates the stabilization of aromatic backbones, the enhancement of electronic conjugations, and the decrease of energy loss. The 1D-COF generates enhanced anodic (92.5-fold) and cathodic (3.2-fold) signals with tripropylamine (TPrA) and K2S2O8 as the anodic and cathodic coreactants, respectively, compared with 2D-COF. The anodic and cathodic ECL efficiencies of 1D-COF are 2.08- and 3.08-fold higher than those of 2D-COF, respectively. According to density functional theory (DFT), the rotational barrier energy (Delta E) of 1D-COF enhances sharply with the increase of dihedral angle, suggesting that the architecture in 1D-COF restrains the intramolecular spin of aromatic chains, which facilitates the decrease of nonradiative transitions and the enhancement of ECL. Furthermore, 1D-COF can be used to construct an ECL biosensor for sensitive detection of dopamine.

Fluorogenic RNA aptamers are valuable tools for cell imaging, but they still suffer from shortcomings such as easy degradation, limited photostability, and low fluorescence enhancement. Molecular crowding conditions enable the stabilization of the structure, promotion of folding, and improvement of activity of functional RNA. Based on artificial RNA condensates, here we present a versatile platform to improve fluorogenic RNA aptamer properties and develop sensors for target analyte imaging in living cells. Using the CUG repeat as a general tag to drive phase separation, various fluorogenic aptamer-based RNA condensates (FLARE) were prepared. We show that the molecular crowding of FLARE can improve the enzymatic resistance, thermostability, photostability, and binding affinity of fluorogenic RNA aptamers. Moreover, the FLARE systems can be modularly engineered into sensors (FLARES), which demonstrate enhanced brightness and sensitivity compared to free sensors dispersed in homogeneous solution. This scalable design principle provides new insights into RNA aptamer property regulation and cellular imaging.

Covalent organic frameworks (COFs) are crystalline porous polymers with the characteristics of a large specific surface area, controllable pore structures, high stability, and low mass density. Herein, we demonstrate the development of an exogenous coreactant-free electrochemiluminescent sensor based on a hydrazone-linked COF for sensing glucose. We synthesized a TFPPy-DMeTHz-COF with the hydrazone bond as the linkage and 2,5-dimethoxyterephthalohydrazide (DMeTHz) and 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) as the monomers. The obtained TFPPy-DMeTHz-COF exhibits high electrochemiluminescence (ECL) efficiency (21.7%) without either the addition of any coreactants or the removal of dissolved O2, and the ECL signal intensity of the TFPPy-DMeTHz-COF is 6.6 and 113-fold higher than those of TFPPy and DMeTHz, respectively. The enhanced ECL emission of the TFPPy-DMeTHz-COF is induced by OH- in PBS, and the ECL signal exhibits linear dependence on the pH value in the range from 3 to 10. When glucose is present, the addition of glucose oxidase (GOx) to the O2-containing solution generates gluconic acid, and the resultant gluconic acid can induce the decrease of the pH value and the quenching of the ECL emission of the TFPPy-DMeTHz-COF. This exogenous coreactant-free electrochemiluminescent sensor exhibits good selectivity, excellent stability, and high sensitivity with a limit of detection (LOD) of 0.031 μM, and it can accurately detect glucose in human serum.

N6-Methyladenosine (m6A) is the most pervasive and evolutionarily conserved epitranscriptomic modification in long noncoding RNA (lncRNA), and its dysregulation may induce aberrant transcription and translation programs. Herein, we demonstrate the methylation-powered assembly of a single quantum dot (QD)-based fluorescence resonance energy transfer (FRET) nanosensor for antibody- and enzyme-free monitoring of locus-specific m6A in clinical tissues. The m6A-sensitive DNAzyme VMC10 is employed to identify a specific m6A site in lncRNA, and it catalyzes the hydrolytic cleavage of unmethylated lncRNA. The cleaved lncRNA fails to trigger the subsequent catalytic hairpin assembly (CHA) reaction due to the energy barrier. In contrast, when m6A-lncRNA is present, the methyl group in m6A protects lncRNA from VMC10-mediated cleavage. With the aid of an assistant probe, the retained intact m6A-lncRNA is released from the VMC10/lncRNA complex and subsequently triggers the CHA reaction, generating abundant AF647/biotin dual-labeled duplexes. The assembly of AF647/biotin dual-labeled duplexes onto 605QD results in efficient FRET between 605QD and AF647. The FRET signal can be simply quantified by single-molecule detection. Notably, this assay can be implemented in an antibody-free and enzyme-free manner. This nanosensor can sensitively quantify target m6A with a detection limit of 0.47 fM, and it can discriminate as low as a 0.001% m6A level from excess coexisting counterparts. Importantly, this nanosensor can monitor the cellular m6A level with single-cell sensitivity and profile target m6A expression in breast cancer and healthy para-cancerous tissues, providing a powerful tool for studying the physiological and pathological functions of m6A.

In the energy transition context, the design and synthesis of high-performance Pt-based photocatalysts with low Pt content and ultrahigh atom-utilization efficiency for hydrogen production are essential. Herein, a facile approach for decorating atomically dispersed Pt cocatalysts having single-atom (SA) and atomic cluster (C) dual active sites on CdS nanorods (PtSA+C /CdS) via atomic layer deposition is reported. The size of the cocatalyst and the spatial intimacy of the cocatalyst active sites are precisely engineered at the atomic scale. The PtSA+C /CdS photocatalysts show the optimized photocatalytic hydrogen evolution activity, achieving a reaction rate of 80.4 mmol h-1 g-1 , which is 1.6- and 7.3-fold higher than those of the PtSA /CdS and PtNP /CdS photocatalysts, respectively. Thorough characterization and theoretical calculations reveal that the enhanced photocatalytic activity is due to a remarkable synergy between SAs and atomic clusters as dual active sites, which are responsible for water adsorption-dissociation and hydrogen desorption, respectively. A similar synergetic effect is found in a representative Pt/TiO2 system, indicating the generality of the strategy. This study demonstrates the significance of the synergy between active sites for enhancing the reaction efficiency, opening a new avenue for the rational design of atomically dispersed photocatalysts with high efficiency.