A large conserved family of small-molecule carboxyl methyltransferases identified from microorganisms.

Small-molecule carboxyl methyltransferases (CbMTs) constitute a small proportion of the reported methyltransferases, but they have received extensive attention due to their important physiological functions. Most of the small-molecule CbMTs isolated to date originate from plants and are members of the SABATH family. In this study, we identified a type of CbMT (OPCMT) from a group of Mycobacteria, which has a distinct catalytic mechanism from the SABATH methyltransferases. The enzyme contains a large hydrophobic substrate-binding pocket (~400 Å3) and utilizes two conserved residues, Thr20 and Try194, to retain the substrate in a favorable orientation for catalytic transmethylation. The OPCMT_like MTs have a broad substrate scope and can accept diverse carboxylic acids enabling efficient production of methyl esters. They are widely (more than 10,000) distributed in microorganisms, including several well-known pathogens, whereas no related genes are found in humans. In vivo experiments implied that the OPCMT_like MTs was indispensable for M. neoaurum, suggesting that these proteins have important physiological functions.

Oxygen vacancy chemistry in oxide cathodes.

Secondary batteries are a core technology for clean energy storage and conversion systems, to reduce environmental pollution and alleviate the energy crisis. Oxide cathodes play a vital role in revolutionizing battery technology due to their high capacity and voltage for oxide-based batteries. However, oxygen vacancies (OVs) are an essential type of defect that exist predominantly in both the bulk and surface regions of transition metal (TM) oxide batteries, and have a crucial impact on battery performance. This paper reviews previous studies from the past few decades that have investigated the intrinsic and anionic redox-mediated OVs in the field of secondary batteries. We focus on discussing the formation and evolution of these OVs from both thermodynamic and kinetic perspectives, as well as their impact on the thermodynamic and kinetic properties of oxide cathodes. Finally, we offer insights into the utilization of OVs to enhance the energy density and lifespan of batteries. We expect that this review will advance our understanding of the role of OVs and subsequently boost the development of high-performance electrode materials for next-generation energy storage devices.

Symmetry-Breaking of Nanoparticle Surface Function Via Conformal DNA Design.

Asymmetric surface functionalization of complex nanoparticles to control their directional self-assembly remains a considerable challenge. Here, we demonstrated a conformal DNA design strategy for flexible remodeling of the surface of complex nanoparticles, taking Au nanobipyramids (AuNBPs) as a model. We sheathed one or both tips of AuNBPs into conformal DNA origami with an exceptionally accurate orientation control. Such asymmetrically and symmetrically distributed surface patches possess regioselective, sequence, and site-specific DNA binding capabilities. As a result, we realized a series of prototypical multicomponent "colloidal molecules" made of AuNBPs and Au nanospheres (AuNSs) with defined directionality and number of "bonding valence" as well as 1D and 3D hierarchical assemblies, e.g., inverse core-satellites of AuNBPs and AuNSs, side-by-side and tip-to-tip linear assemblies of AuNBPs, and 3D helical superstructures of AuNBPs with tunable twists. These findings inspire new opportunities for nanoparticle surface engineering and the high-order self-assembly of nanoarchitectures with higher complexity and broadened functionalities.

Amorphization Activated Multimetallic Pd Alloys for Boosting Oxygen Reduction Catalysis.

Amorphous nanomaterials have drawn extensive attention owing to their unique features, while amorphization on noble metal nanomaterials still remains formidably challenging. Herein, we demonstrate a universal strategy to synthesize amorphous Pd-based nanomaterials from unary to quinary metals through the introduction of phosphorus (P). The amorphous Pd-based nanoparticles (NPs) exhibit generally promoted oxygen reduction reaction (ORR) activity and durability compared with their crystalline counterparts. Significantly, the quinary P-PdCuNiInSn NPs, benefiting from the amorphous structure and multimetallic component effect, exhibit mass activities as high as 1.04 A mgPd-1 and negligible activity decays of 1.8% among the stability tests, which are much better than values for original Pd NPs (0.134 A mgPd-1 and 28.4%). Experimental and theoretical analyses collectively reveal that the synergy of P-induced amorphization and the expansion of metallic components can considerably lower the free energy changes in the rate-determined step, thereby explaining the positive correlation with the catalytic activity.

Strain-Triggered Distinct Oxygen Evolution Reaction Pathway in Two-Dimensional Metastable Phase IrO2 via CeO2 Loading.

A strain engineering strategy is crucial for designing a high-performance catalyst. However, how to control the strain in metastable phase two-dimensional (2D) materials is technically challenging due to their nanoscale sizes. Here, we report that cerium dioxide (CeO2) is an ideal loading material for tuning the in-plane strain in 2D metastable 1T-phase IrO2 (1T-IrO2) via an in situ growth method. Surprisingly, 5% CeO2 loaded 1T-IrO2 with 8% compressive strain achieves an overpotential of 194 mV at 10 mA cm-2 in a three-electrode system. It also retained a high current density of 900 mA cm-2 at a cell voltage of 1.8 V for a 400 h stability test in the proton-exchange membrane device. More importantly, the Fourier transform infrared measurements and density functional theory calculation reveal that the CeO2 induced strained 1T-IrO2 directly undergo the *O-*O radical coupling mechanism for O2 generation, totally different from the traditional adsorbate evolution mechanism in pure 1T-IrO2. These findings illustrate the important role of strain engineering in paving up an optimal catalytic pathway in order to achieve robust electrochemical performance.

Synergistic Effects of PtRhNiFeCu High Entropy Alloy Nanocatalyst for Hydrogen Evolution and Oxygen Reduction Reactions.

The unique properties of high entropy alloy (HEA) catalysts, particularly their severe lattice distortion and the synergistic effect of multiple components, endow them with exceptional multifunctional catalytic performance. Herein, it is revealed for the first time, that the ultrasmall PtRhNiFeCu HEA nanoparticles catalyst shows outstanding catalytic activity for both hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). The catalyst exhibits an impressively low overpotential of 13 mV at 10 mA cm-2, a Tafel slope of 29.6 mV dec-1, and high mass activity of 7.6 A mgPt -1 at -50 mV in alkaline media, and long-term stability of at least 20 h. Moreover, the catalyst also demonstrates effective catalytic activity for acidic ORR with a commendable performance of 1.23 A mgPt -1, much exceeding the commercial Pt/C catalyst. Density functional theory (DFT) calculations unveil that the efficient electrocatalytic performance for HER and ORR can be primarily attributed to the synergistic effect between components tailors and optimizes the electronic structure of PtRhNiFeCu/C HEA, which not only enhances the HER activity through increasing water capture capability, decreasing energetic barrier for water dissociation, and optimizing hydrogen absorption but also initiates non-platinum active sites with high ORR activity, achieving the improved ORR performance.

Compressive Strain in Platinum-Iridium-Nickel Zigzag-Like Nanowire Boosts Hydrogen Catalysis.

Strain effect in the structurally defective materials can contribute to the catalysis optimization. However, it is challenging to achieve the performance improvement by strain modulation with the help of geometrical structure because strain is spatially dependent. Here, a new class of compressively strained platinum-iridium-metal zigzag-like nanowires (PtIrM ZNWs, M = nickel (Ni), cobalt (Co), iron (Fe), zinc (Zn) and gallium (Ga)) is reported as the efficient alkaline hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) catalysts. Particularly, the optimized PtIrNi ZNWs with 3% compressive strain (cs-PtIrNi ZNWs) can achieve the highest HER/HOR performances among all the catalysts investigate. Their HOR mass and specific activities are 3.2/14.4 and 2.6/32.7 times larger than those of PtIrNi NWs and commercial Pt/C, respectively. Simultaneously, they can exhibit the superior stability and high CO resistance for HOR. Further, experimental and theoretical studies collectively reveal that the compressive strain in cs-PtIrNi ZNWs effectively weakens the adsorption of hydroxyl intermediate and modulates the electronic structure, resulting in the weakened hydrogen binding energy (HBE) and moderate hydroxide binding energy (OHBE), beneficial for the improvement of HOR performance. This work highlights the importance of strain tuning in enhancing Pt-based nanomaterials for hydrogen catalysis and beyond.

Modulating 3d Charge State via Halogen Ions in Neighboring Molecules of Metal-Organic Frameworks for Improving Water Oxidation.

Modulating the coordination environment of the metal active center is an effective method to boost the catalytic performances of metal-organic frameworks (MOFs) for oxygen evolution reaction (OER). However, little attention has been paid to the halogen effects on the ligands engineering. Herein, a series of MOFs X─FeNi-MOFs (X = Br, Cl, and F) is constructed with different coordination microenvironments to optimize OER activity. Theoretical calculations reveal that with the increase in electronegativity of halogen ions in terephthalic acid molecular (TPA), the Bader charge of Ni atoms gets larger and the Ni-3d band center and O-2p bands move closer to the Fermi level. This indicates that an increase in ligand negativity of halogen ions in TPA can promote the adsorption ability of catalytic sites to oxygen-containing intermediates and reduce the activation barrier for OER. Experimental also demonstrates that F─FeNi-MOFs exhibit the highest catalytic activity with an ultralow overpotential of 218 mV at 10 mA cm-2, outperforming most otate-of-the-art Fe/Co/Ni-based MOFs catalysts, and the enhanced mass activity by seven times compared with that for the sample before ligands engineering. This work opens a new avenue for the realization of the modulation of NiFe─O bonding by halogen ion in TPA and improves the OER performance of MOFs.

Tuning Crystal Phase of Palladium-Selenium Nanowires for Enhanced Ethylene Glycol Electrocatalytic Oxidation.

Alcohol electrooxidation is pivotal for a sustainable energy economy. However, designing efficient electrocatalysts for this process is still a formidable challenge. Herein, palladium-selenium nanowires featuring distinct crystal phases: monoclinic Pd7Se2 and tetragonal Pd4.5Se for ethylene glycol electrooxidation reaction (EGOR) are synthesized. Notably, the supported monoclinic Pd7Se2 nanowires (m-Pd7Se2 NWs/C) exhibit superior EGOR activity, achieving a mass activity (MA) and specific activity (SA) of 10.4 A mgPd -1 (18.7 mA cm-2), which are 8.0 (6.7) and 10.4 (8.2) times versus the tetragonal Pd4.5Se and commercial Pd/C and surpass those reported in the literature. Furthermore, m-Pd7Se2 NWs/C displays robust catalytic activity for other alcohol electrooxidation. Comprehensive characterization and density functional theory (DFT) calculations reveal that the enhanced electrocatalytic performance is attributed to the increased formation of Pd0 on the high-index facets of the m-Pd7Se2 NWs, which lowers the energy barriers for the C─C bond dissociation in CHOHCHOH* and the CO* oxidation to CO2*. This study provides palladium-based alloy electrocatalysts exhibiting the highest mass activity reported to date for the electrooxidation of ethylene glycol, achieved through the crystalline phase engineering strategy.

Antiferroelectricity-Induced Negative Thermal Expansion in Double Perovskite Pb2 CoMoO6.

Materials with negative thermal expansion (NTE) attract significant research attention owing to their unique physical properties and promising applications. Although ferroelectric phase transitions leading to NTE are widely investigated, information on antiferroelectricity-induced NTE remains limited. In this study, single-crystal and polycrystalline Pb2 CoMoO6 samples are prepared at high pressure and temperature conditions. The compound crystallizes into an antiferroelectric Pnma orthorhombic double perovskite structure at room temperature owing to the opposite displacements dominated by Pb2+ ions. With increasing temperature to 400 K, a structural phase transition to cubic Fm-3m paraelectric phase occurs, accompanied by a sharp volume contraction of 0.41%. This is the first report of an antiferroelectric-to-paraelectric transition-induced NTE in Pb2 CoMoO6 . Moreover, the compound also exhibits remarkable NTE with an average volumetric coefficient of thermal expansion αV = -1.33 × 10-5 K-1 in a wide temperature range of 30-420 K. The as-prepared Pb2 CoMoO6 thus serves as a prototype material system for studying antiferroelectricity-induced NTE.

Combined therapy of CAR-IL-15/IL-15Rα-T cells and GLIPR1 knockdown in cancer cells enhanced anti-tumor effect against gastric cancer.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has shown remarkable responses in hematological malignancies with several approved products, but not in solid tumors. Patients suffer from limited response and tumor relapse due to low efficacy of CAR-T cells in the complicated and immunosuppressive tumor microenvironment. This clinical challenge has called for better CAR designs and combined strategies to improve CAR-T cell therapy against tumor changes. METHODS: In this study, IL-15/IL-15Rα was inserted into the extracellular region of CAR targeting mesothelin. In-vitro cytotoxicity and cytokine production were detected by bioluminescence-based killing and ELISA respectively. In-vivo xenograft mice model was used to evaluate the anti-tumor effect of CAR-T cells. RNA-sequencing and online database analysis were used to identify new targets in residual gastric cancer cells after cytotoxicity assay. CAR-T cell functions were detected in vitro and in vivo after GLI Pathogenesis Related 1 (GLIPR1) knockdown in gastric cancer cells. Cell proliferation and migration of gastric cancer cells were detected by CCK-8 and scratch assay respectively after GLIPR1 were overexpressed or down-regulated. RESULTS: CAR-T cells constructed with IL-15/IL-15Rα (CAR-ss-T) showed significantly improved CAR-T cell expansion, cytokine production and cytotoxicity, and resulted in superior tumor control compared to conventional CAR-T cells in gastric cancer. GLIPR1 was up-regulated after CAR-T treatment and survival was decreased in gastric cancer patients with high GLIPR1 expression. Overexpression of GLIPR1 inhibited cytotoxicity of conventional CAR-T but not CAR-ss-T cells. CAR-T treatment combined with GLIPR1 knockdown increased anti-tumor efficacy in vitro and in vivo. CONCLUSIONS: Our data demonstrated for the first time that this CAR structure design combined with GLIPR1 knockdown in gastric cancer improved CAR-T cell-mediated anti-tumor response.

Spectroscopic Evidence of Kondo-Induced Quasiquartet in CeRh_{2}As_{2}.

CeRh_{2}As_{2} is a new multiphase superconductor with strong suggestions for an additional itinerant multipolar ordered phase. The modeling of the low-temperature properties of this heavy-fermion compound requires a quartet Ce^{3+} crystal-field ground state. Here, we provide the evidence for the formation of such a quartet state using x-ray spectroscopy. Core-level photoelectron and x-ray absorption spectroscopy confirm the presence of Kondo hybridization in CeRh_{2}As_{2}. The temperature dependence of the linear dichroism unambiguously reveals the impact of Kondo physics for coupling the Kramer's doublets into an effective quasiquartet. Nonresonant inelastic x-ray scattering data find that the |Γ_{7}^{-}⟩ state with its lobes along the 110 direction of the tetragonal structure (xy orientation) contributes most to the multiorbital ground state of CeRh_{2}As_{2}.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Rational design, synthesis and biological evaluation of novel HIV-1 protease inhibitors containing 2-phenylacetamide derivatives as P2 ligands with potent activity against DRV-Resistant HIV-1 variants.

A novel kind of potent HIV-1 protease inhibitors, containing diverse hydroxyphenylacetic acids as the P2-ligands and 4-substituted phenyl sulfonamides as the P2' ligands, were designed, synthesized and evaluated in this work. Majority of the target compounds exhibited good to excellent activity against HIV-1 protease with IC50 values below 200 nM. In particular, compound 18d with a 2-(3,4-dihydroxyphenyl) acetamide as the P2 ligand and a 4- methoxybenzene sulfonamide P2' ligand exhibited inhibitory activity IC50 value of 0.54 nM, which was better than that of the positive control darunavir (DRV). More importantly, no significant decline of the potency against HIV-1DRVRS (DRV-resistant mutation) and HIV-1NL4_3 variant (wild type) for 18d was detected. The molecular docking study of 18d with HIV-1 protease (PDB-ID: 1T3R, www.rcsb.org) revealed possible binding mode with the HIV-1 protease. These results suggested the validity of introducing phenol-derived moieties into the P2 ligand and deserve further optimization which was of great value for future discovery of novel HIV-1 protease.

High-Pressure Synthesis of Semiconducting PbCu3Mn4O12 with Near-Room-Temperature Ferrimagnetic Order.

A transition-metal oxide of PbCu3Mn4O12 was prepared at 1523 K and 10 GPa. An A-site-ordered quadruple perovskite structure with the space group Im3̅ is assigned for this compound. Based on bond-valence-sum calculations and X-ray absorption spectroscopy, the charge combination is determined to be PbCu32+Mn44+O12. Due to Cu2+(↑)-Mn4+(↓) antiferromagnetic coupling, a near-room-temperature ferrimagnetic phase transition is observed at approximately 287 K. PbCu3Mn4O12 exhibits a semiconducting electric transport property with the energy band gap Eg ≈ 0.2 eV. In addition, considerable low-field magnetoresistance effects are observed at lower temperatures. This study provides an intrinsic near-room-temperature ferrimagnetic semiconductor that exhibits potential applications in next-generation spintronic devices.

High-Pressure Synthesis of Quadruple Perovskite Oxide CaCu3Cr2Re2O12 with a High Ferrimagnetic Curie Temperature.

An AA'3B2B'2O12-type quadruple perovskite oxide of CaCu3Cr2Re2O12 was synthesized at 18 GPa and 1373 K. Both an A- and B-site ordered quadruple perovskite crystal structure was observed, with the space group Pn-3. The valence states are verified to be CaCu32+Cr23+Re25+O12 by bond valence sum calculations and synchrotron X-ray absorption spectroscopy. The spin interaction among Cu2+, Cr3+, and Re5+ generates a ferrimagnetic transition with the Curie temperature (TC) at about 360 K. Moreover, electric transport properties and specific heat data suggest the presence of a half-metallic feature for this compound. The present study provides a promising quadruple perovskite oxide with above-room-temperature ferrimagnetism and possible half-metallic properties, which shows potential in the usage of spintronic devices.

Robust Crystal Phase Separation with Distinct Charge, Orbital, and Spin Orders in AgMn7O12.

An AA'3B4O12-type A-site-ordered quadruple perovskite oxide AgMn7O12 was prepared by high-pressure and high-temperature methods. At room temperature, the compound crystallizes into a cubic Im3̅ symmetry with a charge distribution of AgMn33+Mn43.5+O12. With the temperature decreasing to TCO,OO ≈ 180 K, the compound undergoes a structural phase transition toward a monoclinic C2/m symmetry, giving rise to a B-site charge- and orbital-ordered AgMn33+Mn23+Mn24+O12 phase. Moreover, this charge-/orbital-ordered main phase coexists with the initial cubic AgMn33+Mn43.5+O12 phase in the wide temperature range we measured. The charge-/orbital-ordered phase shows two antiferromagnetic phase transitions near 125 and 90 K, respectively. Short-range ferromagnetic correlations are found to occur for the initial B-site mixed cubic phase around 35 K. Because of the robust phase separation, considerable magnetoresistance effects are observed below TCO,OO in AgMn7O12.

Observation of Enhanced Long-Range Ferromagnetic Order in B-Site Ordered Double Perovskite Oxide Cd2CrSbO6.

A B-site ordered double perovskite oxide Cd2CrSbO6 was synthesized under high-pressure and high-temperature conditions. The compound crystallizes to a monoclinic structure with a space group of P21/n. The charge configuration is confirmed to be that of Cd2+/Cr3+/Sb5+. The magnetic Cr3+ ions form a tetrahedral structural frustrated lattice, while a long-range ferromagnetic phase transition is found to occur at TC = 16.5 K arising from the superexchange interaction via the Cr-O-Cd-O-Cr pathway. Electrical transport measurements indicate that Cd2CrSbO6 is an insulator that can be described by the Mott 3D variable range hopping mechanism. First-principles calculations reproduce well the ferromagnetic and insulating ground state of Cd2CrSbO6 with an energy band gap of 1.55 eV. The intrinsic ferromagnetic insulating nature qualifies Cd2CrSbO6 as a promising candidate for possible spintronics applications.

Association of gastroesophageal junction laxity and gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease is a prevalent condition with significant clinical variability, complicating its evaluation and treatment. The gastroesophageal flap valve is a fundamental evaluation method, but have shown limitations in specificity and reliance on subjective endoscopists' experience. Recent insights suggest that gastroesophageal junction laxity may offer an objective and quantifiable measurement for the presence of gastroesophageal reflux disease. METHODS: This retrospective study analyzed data from 401 patients who underwent comprehensive evaluations, including a symptom questionnaire, endoscopy, pH-impedance monitoring, high-resolution manometry, and treatment directions, between January 1, 2022 and October 31, 2023. Gastroesophageal junction laxity was assessed using a modified approach based on endoscopic image analysis, with the diameter of endoscope as reference to estimate the long diameter of the laxity ring. The independent association of gastroesophageal junction laxity with pathologic acid exposure, esophagitis, and hiatal hernia were assessed by adjusting with age and sex. RESULTS: The mean age was 44.5 ± 5.5 years old, and 49.9% (200/401) were male. The most common symptoms (≥ 1 point) were acid regurgitation (333/401, 83.0%), heartburn (315/401, 78.6%), belching (278/401, 69.3%), bloating (241/401, 60.1%), and globus sensation (241/401, 60.1%). The gastroesophageal junction laxity was significantly associated with pathologic acid exposure, esophagitis, hiatal hernia, and lower esophageal sphincter resting pressure. Notably, with the increase in gastroesophageal junction laxity, the rates of pathologic acid exposure, esophagitis, and hiatal hernia increased gradually, the lower esophageal sphincter resting pressure decreased gradually. The gastroesophageal junction laxity was independent associated with pathologic acid exposure (OR = 2.33, 95%CI 1.77-3.07, p < 0.001), esophagitis (OR = 2.10, 95%CI 1.62-2.73, p < 0.001), and hiatal hernia (high-resolution manometry: OR = 3.39, 95%CI: 2.46-4.67, p < 0.001) (endoscopy: OR = 21.65, 95%CI 11.70-40.06, p < 0.001). CONCLUSION: The gastroesophageal junction laxity was significantly associated with the indicators of pathophysiology in gastroesophageal reflux disease.

Nanotip-Induced Electric Field for Hydrogen Catalysis.

Local electric field induced by the lightning-rod effect attracts great attention for regulating the local microenvironment and electronic properties of active sites. Nevertheless, local electric-field-assisted applications are mainly limited to metals with strong surface plasmonic resonance properties (e.g., Au, Ag, and Cu). Herein, we fabricate RuCu snow-like nanosheets (SNSs) with high-curvature nanotips for enhancing the hydrogen oxidation reaction (HOR) and hydrogen evolution reaction (HER). Theoretical simulations show that RuCu SNSs can induce a strong local electric field around the sharp nanotips, which favors the accumulation of OH- for HOR and H+ for HER. Cu incorporation can modulate the binding strength of OH* and H*, leading to significantly enhanced HOR and HER performance. Impressively, the mass activity of RuCu SNSs for alkaline HOR is 31.3 times higher than that of RuCu nanocrystals without sharp tips. Besides, the required overpotential for reaching 10 mA cm-2 during HER over RuCu SNSs is 14.0 mV.