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A new germacrane-type sesquiterpenoid (1) and a new alkamide (2), as well as six known compounds (3-8) were isolated from the capitula of Chrysanthemum morifolium cv. Fubaiju. The new structures were elucidated by comprehensive spectroscopic analysis and quantum chemical calculations. The known structures were characterised via 1D NMR data compared with the already existing literature data. Among the isolates, compound 5 showed inhibitory activity against human lung cancer A549 cells and human hepatoma HepG2 cells with the IC50 values of 19.50 ± 1.23 and 23.24 ± 1.30 µM, respectively, and compound 8 exhibited inhibitory effect on RSV infection with IC50 value of 12.50 ± 1.02 µM.

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The extracellular matrix (ECM) plays a crucial role in maintaining cell morphology and facilitating intercellular signal transmission within the human body. ECM has been extensively utilized for tissue injury repair. However, the consideration of factor gradients during ECM preparation has been limited. In this study, we developed a novel approach to generate sheet-like ECM with a continuous gradient of stromal cell-derived factor-1 (SDF1α). Briefly, we constructed fibroblasts to overexpress SDF1α fused with the collagen-binding domain (CBD-SDF1α), and cultured these cells on a slanted plate to establish a gradual density cell layer at the bottom surface. Subsequently, excess parental fibroblasts were evenly distributed on the plate laid flat to fill the room between cells. Following two weeks of culture, the monolayer cells were lyophilized to form a uniform ECM sheet possessing a continuous gradient of SDF1α. This engineered ECM material demonstrated its ability to guide oriented migration of human umbilical cord mesenchymal stem cells (hUCMSCs) on the ECM sheet. Our simple yet effective method holds great potential for advancing research in regenerative medicine.

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Bluetongue disease is an infectious disease transmitted by Culicoides as vectors, mainly infecting ruminants. Because ruminants play an important role in animal husbandry in China, the outbreak of bluetongue disease can cause serious economic losses. Maxent model was applied to predict the distribution of bluetongue in China based on the data derived from domestic and foreign academic literature databases including CNKI, Wanfang Database, PubMed, Web of Science and Google Scholar. The results showed that annual mean temperature (BIO1), precipitation in driest month (BIO14), sheep density (SD) and altitude (Elev) were the relevant variables of bioclimatic suitable zones for bluetongue disease. Precipitation in wettest month (BIO13), BIO1, BIO14, Elev were the main variables affecting the habitat of the bluetongue vector Culicoides. The most suitable climate for bluetongue infection occurs in southern China, central China and parts of Xinjiang. The suitable living areas of Culicoides are mainly located in southern, central and eastern China, and the overlap of the two suitable areas is high. The study suggested that southern, central, and eastern China are high-risk areas for bluetongue due to the significant overlap of suitable habitats for both the disease and its vector. Implementing effective surveillance and targeted control strategies in these regions is crucial for mitigating the impact of bluetongue disease.

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Background: Manual planning of scans in clinical magnetic resonance imaging (MRI) exhibits poor accuracy, lacks consistency, and is time-consuming. Meanwhile, classical automated scan plane positioning methods that rely on certain assumptions are not accurate or stable enough, and are computationally inefficient for practical application scenarios. This study aims to develop and evaluate an effective, reliable, and accurate deep learning-based framework that incorporates prior physical knowledge for automatic head scan plane positioning in MRI. Methods: A deep learning-based end-to-end automated scan plane positioning framework has been developed for MRI head scans. Our model takes a three-dimensional (3D) pre-scan image input, utilizing a cascaded 3D convolutional neural network to detect anatomical landmarks from coarse to fine. And then, with the determined landmarks, accurate scan plane localization can be achieved. A multi-scale spatial information fusion module was employed to aggregate high- and low-resolution features, combined with physically meaningful point regression loss (PRL) function and direction regression loss (DRL) function. Meanwhile, we simulate complex clinical scenarios to design data augmentation strategies. Results: Our proposed approach shows good performance on a clinically wide range of 229 MRI head scans, with a point-to-point absolute error (PAE) of 0.872 mm, a point-to-point relative error (PRE) of 0.10%, and an average angular error (AAE) of 0.502°, 0.381°, and 0.675° for the sagittal, transverse, and coronal planes, respectively. Conclusions: The proposed deep learning-based automated scan plane positioning shows high efficiency, accuracy and robustness when evaluated on varied clinical head MRI scans with differences in positioning, contrast, noise levels and pathologies.

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The CONSTANS/CONSTANS-Like (CO/COL) family has been shown to play important roles in flowering, stress tolerance, fruit development and ripening in higher plants. In this study, three COL genes, MiCOL6, MiCOL7A and MiCOL7B, which each contain only one CCT domain, were isolated from mango (Mangifera indica), and their functions were investigated. MiCOL7A and MiCOL7B were expressed mainly at 20 days after flowering (DAF), and all three genes were highly expressed during the flowering induction period. The expression levels of the three genes were affected by light conditions, but only MiCOL6 exhibited a clear circadian rhythm. Overexpression of MiCOL6 promoted earlier flowering, while overexpression of MiCOL7A or MiCOL7B delayed flowering compared to that in the control lines of Arabidopsis thaliana under long-day (LD) and short-day (SD) conditions. Overexpressing MiCOL6, MiCOL7A or MiCOL7B in transgenic plants increased superoxide dismutase (SOD) and proline levels, decreased malondialdehyde (MAD) levels, and improved survival under drought and salt stress. In addition, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses showed that the MiCOL6, MiCOL7A and MiCOL7B proteins interact with several stress- and flower-related proteins. This work demonstrates the functions of MiCOL6, MiCOL7A and MiCOL7B and provides a foundation for further research on the role of mango COL genes in flowering regulation and the abiotic stress response.

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As promising delivery systems, smart microcapsules have garnered significant attention owing to their targeted delivery loaded with diverse active materials. By precisely manipulating fluids on the micrometer scale, microfluidic has emerged as a powerful tool for tailoring delivery systems based on potential applications. The desirable characteristics of smart microcapsules are associated with encapsulation capacity, targeted delivery capability, and controlled release of encapsulants. In this review, we briefly describe the principles of droplet-based microfluidics for smart microcapsules. Subsequently, we summarize smart microcapsules as delivery systems for efficient encapsulation and focus on target delivery patterns, including passive targets, active targets, and microfluidics-assisted targets. Additionally, based on release mechanisms, we review controlled release modes adjusted by smart membranes and on/off gates. Finally, we discuss existing challenges and potential implications associated with smart microcapsules.

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Unraveling the configuration-activity relationship and synergistic enhancement mechanism (such as real active center, electron spin-state, and d-orbital energy level) for triatomic catalysts, as well as their intrinsically bifunctional oxygen electrocatalysis, is a great challenge. Here we present a triatomic catalyst (TAC) with a trinuclear active structure that displays extraordinary oxygen electrocatalysis for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), greatly outperforming the counterpart of single-atom and diatomic catalysts. The aqueous Zn-air battery (ZAB) equipped with a TAC-based cathode exhibits extraordinary rechargeable stability and ultrarobust cycling performance (1970 h/3940 cycles at 2 mA cm-2, 125 h/250 cycles at 10 mA cm-2 with negligible voltage decay), and the quasi-solid-state ZAB displays outstanding rechargeability and low-temperature adaptability (300 h/1800 cycles at 2 mA cm-2 at -60 °C), outperforming other state-of-the-art ZABs. The experimental and theoretical analyses reveal the symmetry-breaking CoN4 configuration under incorporation of neighboring metal atoms (Fe and Cu), which leads to d-orbital modulation, a low-shift d band center, weakened binding strength to the oxygen intermediates, and decreased energy barrier for bifunctional oxygen electrocatalysis. This rational tricoordination design as well as an in-depth mechanism analysis indicate that hetero-TACs can be promisingly applied in various electrocatalysis applications.

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Pork is one of the most commonly consumed meats, and its safety has always been a concern. Recently, safety incidents caused by chemical or biological contamination such as drug residues, heavy metals, and pathogenic microorganisms in pork have been reported, and the safety of pork is a cause for concern. Salmonella spp. is one of the important foodborne pathogens that threaten human health. Pork is a high-risk vector food for Salmonella spp. infection. The assessment of the safety risk of Salmonella spp. in pork is conducive to the prevention of related foodborne diseases. In this paper, risk assessment models for Salmonella spp. in meat were developed. The quantitative risk assessment model for Salmonella spp. based on the pork supply chain showed that the annual number of cases of salmonellosis due to pork consumption in China is approximately 27 per 10,000 males and 24 per 10,000 females. Sensitivity analysis showed that the main factors affecting the risk of Salmonella spp. in pork were the display temperature, display time, and Salmonella spp. contamination concentration in pork at the sale.

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AIM: Aggravated neuronal loss, caused mainly by neuronal apoptosis, is observed in the brain of patients with Alzheimer's disease (AD) and animal models of AD. A truncated form of Dual-specific and tyrosine phosphorylation-regulated protein kinase 1A (Dyrk1A) plays a vital role in AD pathogenesis. Downregulation of anti-apoptotic Bcl-xL is tightly correlated with neuronal loss in AD. However, the molecular regulation of neuronal apoptosis and Bcl-x expression by Dyrk1A in AD remains largely elusive. Here, we aimed to explore the role and molecular mechanism of Dyrk1A in apoptosis. METHODS: Cell Counting Kit-8 (CCK8), flow cytometry, and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to check apoptosis. The cells, transfected with Dyrk1A or/and ASF with Bcl-x minigene, were used to assay Bcl-x expression by RT-PCR and Western blots. Co-immunoprecipitation, autoradiography, and immunofluorescence were conducted to check the interaction of ASF and Dyrk1A. Gene set enrichment analysis (GSEA) of apoptosis-related genes was performed in mice overexpressing Dyrk1A (TgDyrk1A) and AD model 5xFAD mice. RESULTS: Dyrk1A promoted Bcl-xS expression and apoptosis. Splicing factor ASF promoted Bcl-x exon 2b inclusion, leading to increased Bcl-xL expression. Dyrk1A suppressed ASF-mediated Bcl-x exon 2b inclusion via phosphorylation. The C-terminus deletion of Dyrk1A facilitated its binding and kinase activity to ASF. Moreover, Dyrk1a1-483 further suppressed the ASF-mediated Bcl-x exon 2b inclusion and aggravated apoptosis. The truncated Dyrk1A, increased Bcl-xS, and enrichment of apoptosis-related genes was observed in the brain of 5xFAD mice. CONCLUSIONS: We speculate that increased Dyrk1A and truncated Dyrk1A may aggravate neuronal apoptosis by decreasing the ratio of Bcl-xL/Bcl-xS via phosphorylating ASF in AD.

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Long-term exposure to pesticides is associated with the incidence of cancer. With the exponential increase in the number of new pesticides being synthesized, it becomes more and more important to evaluate the toxicity of pesticides by means of simulated calculations. Based on existing data, machine learning methods can train and model the predictions of the effects of novel pesticides, which have limited available data. Combined with other technologies, this can aid the synthesis of new pesticides with specific active structures, detect pesticide residues, and identify their tolerable exposure levels. This article mainly discusses support vector machines, linear discriminant analysis, decision trees, partial least squares, and algorithms based on feedforward neural networks in machine learning. It is envisaged that this article will provide scientists and users with a better understanding of machine learning and its application prospects in pesticide toxicity assessment.

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Norovirus (NoV) and hepatitis A virus (HAV) pose a considerable health risk worldwide. In recent years, many cases of virus infection caused by virus-contaminated strawberries have occurred worldwide. This study applied a critical control point system to analyze the main hazards during the production and marketing of strawberries imported into China and explore the key control points in the whole process. To further evaluate the risks in the supply chain, the established quantitative microbial risk assessment (QMRA) was used to determine the probability that residents would be infected with viruses after consuming imported strawberries. It was found that the risk of virus contamination from imported strawberries was low, and the virus contamination mainly results from water resources and personnel. This research helps the regulatory authorities formulate strategies to ensure the long-term microbial safety of imported strawberries. In addition, the methods may prove useful in evaluating the risks of other agricultural produce.

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Investigating brain activity is essential for exploring taste-experience related cues. The paper aimed to explore implicit (unconscious) emotional or physiological responses related to taste experiences using scalp electroencephalogram (EEG). We performed implicit measures of tastants of differing perceptual types (bitter, salty, sour and sweet) and intensities (low, medium, and high). The results showed that subjects were partially sensitive to different sensory intensities, i.e., for high intensities, taste stimuli could induce activation of different rhythm signals in the brain, with α and θ bands possibly being more sensitive to different taste types. Furthermore, the neural representations and corresponding sensory qualities (e.g., "sweet: pleasant" or "bitter: unpleasant") of different tastes could be discriminated at 250-1,500 ms after stimulus onset, and different tastes exhibited distinct temporal dynamic differences. Source localization indicated that different taste types activate brain areas associated with emotional eating, reward processing, and motivated tendencies, etc. Overall, our findings reveal a larger sophisticated taste map that accounted for the diversity of taste types in the human brain and assesses the emotion, reward, and motivated behavior represented by different tastes. This study provided basic insights and a perceptual foundation for the relationship between taste experience-related decisions and the prediction of brain activity.

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Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.

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Elevational gradients provide an excellent opportunity to assess biodiversity patterns and community structure. Previous studies mainly focus on higher elevations or are limited to small areas in mountainous regions. Little information can be found on amphibian biodiversity in middle- and low-elevational areas, hence our study was devoted to filling up the current gaps in these research areas. To understand the variability of biodiversity of amphibian species in the Fujian Junzifeng National Nature Reserve in eastern China, our study included taxonomic and phylogenetic components to describe the various patterns of regional and elevational distribution. The results showed that (1) most of the taxonomic and phylogenetic diversity metrics were correlated; with regard to the surveyed area, Faith's phylogenetic diversity index (PD) and net relatedness index (NRI) were positively correlated with the Shannon-Wiener index (H'), Margalef index (DMG), and species richness (S), while negatively with the Pielou index; whereas for elevation, only the Pielou index was positively correlated with the nearest taxon index (NTI), but negatively with other indices; (2) taxonomic and phylogenetic diversities did not differ among the three survey locations but differed significantly along the elevational gradient; Simpson index, H', S, and DMG had a hump-shaped relationship with elevations, and PD decreased gradually with the increase in elevation, whereas NRI and NTI sharply increased at the elevation above 900 m; (3) the species range size and the corresponding midpoint of amphibians were affected by a strong phylogenetic signal, which supports the elevational Rapoport's rule upon removal of Pachytriton brevipes and Boulenophrys sanmingensis from the study.

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Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide-optimized and EVs-delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)-triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short-acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.

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Calcium-activated chloride channels (CaCCs) are chloride channels that are regulated according to intracellular calcium ion concentrations. The channel protein ANO1 is widely present in cells and is involved in physiological activities including cellular secretion, signaling, cell proliferation and vasoconstriction and diastole. In this study, the ANO1 inhibitors were investigated with machine learning and molecular simulation. Two-dimensional structure-activity relationship (2D-SAR) and three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for the qualitative and quantitative prediction of ANO1 inhibitors. The results showed that the prediction accuracies of the model were 85.9% and 87.8% for the training and test sets, respectively, and 85.9% and 87.8% for the rotating forest (RF) in the 2D-SAR model. The CoMFA and CoMSIA methods were then used for 3D QSAR modeling of ANO1 inhibitors, respectively. The q2 coefficients for model cross-validation were all greater than 0.5, implying that we were able to obtain a stable model for drug activity prediction. Molecular docking was further used to simulate the interactions between the five most promising compounds predicted by the model and the ANO1 protein. The total score for the docking results between all five compounds and the target protein was greater than 6, indicating that they interacted strongly in the form of hydrogen bonds. Finally, simulations of amino acid mutations around the docking cavity of the target proteins showed that each molecule had two or more sites of reduced affinity following a single mutation, indicating outstanding specificity of the screened drug molecules and their protein ligands.

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The frequently mutated phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene is associated with multiple tumors and endocytosis of viruses. Identification of muted nucleotides at the hotspot can help in finding the susceptible people who are vulnerable to cancers and viruses. Herein, a simple enzyme-free colorimetric method is developed for the quick detection of PIK3CA gene mutations. The main mechanism lies in the dissimilar interactions between praseodymia nanorods and different nucleotides, as well as the underlying oxidase-mimicking characteristics of praseodymia. With rational designs of probes and processes, this method has great potential for expanded applications in the screening of mutations in other genes of interest.

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The rapid development of portable and wearable electronics has given rise to new challenges and provoked research in flexible, lightweight, and affordable energy storage devices. Flexible solid-state metal-air batteries (FSSMABs) are considered promising candidates, owing to their large energy density, mechanical flexibility, and durability. However, the practical applications of FSSMABs require further improvement to meet the demands of long-term stability, high power density, and large operating voltage. This Review presents a detailed discussion of innovative electrocatalysts for the air cathode, followed by a sequential overview of high-performance solid-state electrolytes and metal anodes, and a summary of the current challenges and future perspectives of FSSMABs to promote practical application and large-scale commercialization in the near future.

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MicroRNA (miRNA)-based therapies have shown great potential in the repair of spinal cord injury (SCI). MicroRNA 21 (miR21) has been proven to have an essential protective effect on SCI. However, there are some challenges for miRNAs application due to their easy degradation and ineffective cell penetration. As natural vesicles, exosomes were considered ideal carriers for miRNAs delivery for their advantages of low immunogenicity, inherent stability and tissue/cell penetration. However, poor targeting and the low capacity of specific miRNAs impede their practical applications. This study aims to develop a type of genetically engineered miR21-loaded exosomes that can be entrapped in collagen-I (Col-I) scaffold to repair SCI. The collagen-binding domain (CBD)-fused lysosome-associated membrane glycoprotein 2b (Lamp2b) protein (CBD-LP) and miR21 were overexpressed in host HEK293T (293T) cells that were used to produce engineered miR21-loaded exosomes. The CBD peptide fused in Lamp2b on the exosome surface can stably tether exosomes to Col-I scaffold, facilitate the retention of miR21-loaded exosomes in lesion sites, promote the sustained release of miR21 to cells. Finally, a functionalized Col-I scaffold biomaterial enriched with miR21-loaded exosomes was developed and it could benefit the repair of SCI. STATEMENT OF SIGNIFICANCE: MiRNA-based therapeutics have promising potential in spinal cord injury (SCI) repair. However, easy degradation and ineffective cell penetration impede miRNAs application. Exosomes are natural vehicles for miRNAs delivery but face the challenge of diffusion in vivo. Here, the collagen-binding domain (CBD)-fused Lamp2b and miR21 were overexpressed in HEK293T cells to produce miR21-loaded and CBD-modified exosomes (CBD-LP-miR21-EXOs). The CBD modified on the exosome surface can stably tether exosomes to collagen-I scaffold to form functionalized CBD-LP-miR21-EXO-Col scaffold that can facilitate the retention of miR21-loaded exosomes, promote the sustained release of miR21 to cells and finally benefit SCI repair. Furthermore, this type of functionalized collagen-I materials can be widely applied for other tissue injury repairs by enriching the CBD-LP-EXOs loaded with appropriate miRNAs.

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The efficiency of direct methanol fuel cell (DMFC) is largely determined by the activity and durability of methanol oxidation reaction (MOR) catalysts. Herein, we present a CO-resilient MOR catalyst of palladium-tin nano-alloy anchored on Se-doped MXene (PdSn0.5 /Se-Ti3 C2 ) via a progressive one-step electrochemical deposition strategy. MOR mass activity resulting from Pd/Se-Ti3 C2 catalyst (1046.2 mA mg-1 ) is over 2-fold larger than that of Pd/Ti3 C2 , suggesting that the introduction of Se atoms on MXene might accelerate the reaction kinetics. PdSn0.5 /Se-Ti3 C2 with Se-doping progress of MXene and the cooperated Pd-Sn sites has a superior MOR mass activity (4762.8 mA mg-1 ), outperforming many other reported Pd-based catalysts. Both experimental results and theoretical calculation reveal that boosted electron interaction of metal crystals with Se-doped MXene and optimized distribution of Pd-Sn sites can modulate the d band center, reduce adsorption energies of CO* at Pd site and enhance OH* generation at Sn site, resulting in highly efficient removal of CO intermediates by reaction with neighboring OH species on adjacent Sn sites.