Biomimetic Exosome-Sheathed Magnetic Mesoporous Anchor with Modification of Glucose Oxidase for Synergistic Targeting and Starving Tumor Cells.

Efficient protection and precise delivery of biomolecules are of critical importance in the intervention and therapy of various diseases. Although diverse specific marker-functionalized drug carriers have been developed rapidly, current approaches still encounter substantial challenges, including strong immunogenicity, limited target availability, and potential side effects. Herein, we developed a biomimetic exosome-sheathed magnetic mesoporous anchor modified with glucose oxidase (MNPs@mSiO2-GOx@EM) to address these challenges and achieve synergistic targeting and starving of tumor cells. The MNPs@mSiO2-GOx@EM anchor integrated the unique characteristics of different components. An external decoration of exosome membrane (EM) with high biocompatibility contributed to increased phagocytosis prevention, prolonged circulation, and enhanced recognition and cellular uptake of loaded particles. An internal coated magnetic mesoporous core with rapid responsiveness by the magnetic field guidance and large surface area facilitated the enrichment of nanoparticles at the specific site and provided enough space for modification of glucose oxidase (GOx). The inclusion of GOx in the middle layer accelerated the energy-depletion process within cells, ultimately leading to the starvation and death of target cells with minimal side effects. With these merits, in vitro study manifested that our nanoplatform not only demonstrated an excellent targeting capability of 94.37% ± 1.3% toward homotypic cells but also revealed a remarkably high catalytical ability and cytotoxicity on tumor cells. Assisted by the magnetic guidance, the utilization of our anchor obviously inhibits the tumor growth in vivo. Together, our study is promising to serve as a versatile method for the highly efficient delivery of various target biomolecules to intended locations due to the fungibility of exosome membranes and provide a potential route for the recognition and starvation of tumor cells.

The discovery of a novel single-function intermolecular Diels-Alder enzyme for the biosynthesis of hetero-dimer lithocarpins.

The deep-sea fungus Phomopsis lithocarpus FS508 produces tenellone-macrolide conjugated hetero-dimer lithocarpins A-G with anti-tumor activities. The deficiency of new intermolecular Diels-Alder (DA) enzymes hindered the development of new bioactive hetero-dimers. A novel single-function intermolecular DA enzyme, g7882, was initially discovered in this study. The deletion of g7882 led to the disappearance of lithocarpin A and an increase in precursor level . the overexpression of g7882 significantly improved lithocarpin A yield. The in vitro function of g7882DA was also confirmed by biochemical reaction using tenellone B as a substrate. Additionally, the knockout of KS modules of PKS in cluster 41 and cluster 81 (lit cluster) eliminated the production of lithocarpins, which firstly explains the biosynthetic process of hetero-dimer lithocarpins mediated by DA enzyme in FS508. Furthermore, the removal of a novel acetyltransferase GPAT in cluster 41 and the oxidoreductase, prenyltransferase in cluster81 resulted in the reduction of lithocarpin A in P. lithocarpus. The overexpression of gpat in P. lithocarpus FS508 improved the yield of lithocarpin A significantly and produced a new tenellone derivative lithocarol G. This study offers a new DA enzyme tool for the biosynthesis of novel hetero-dimer and biochemical clues for the biosynthetic logic elucidation of lithocarpins.

New horizons for the role of RNA N6-methyladenosine modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancy, presenting a formidable challenge to the medical community owing to its intricate pathogenic mechanisms. Although current prevention, surveillance, early detection, diagnosis, and treatment have achieved some success in preventing HCC and controlling overall disease mortality, the imperative to explore novel treatment modalities for HCC remains increasingly urgent. Epigenetic modification has emerged as pivotal factors in the etiology of cancer. Among these, RNA N6-methyladenosine (m6A) modification stands out as one of the most prevalent, abundant, and evolutionarily conserved post-transcriptional alterations in eukaryotes. The literature underscores that the dynamic and reversible nature of m6A modifications orchestrates the intricate regulation of gene expression, thereby exerting a profound influence on cell destinies. Increasing evidence has substantiated conspicuous fluctuations in m6A modification levels throughout the progression of HCC. The deliberate modulation of m6A modification levels through molecular biology and pharmacological interventions has been demonstrated to exert a discernible impact on the pathogenesis of HCC. In this review, we elucidate the multifaceted biological functions of m6A modifications in HCC, and concurrently advancing novel therapeutic strategies for the management of this malignancy.

Immunomagnetic capture and traceless release of native tumor-derived exosomes from human plasma for exploring interaction with recipient cells by aptamer-functionalized nanoflowers.

BACKGROUND: Tumor-derived exosomes (TEXs) play an important role in the development process of cancer, which can transport a large number of carcinogenic molecules to normal cells, and subsequently promote tumor metastasis. However, TEXs that were utilized in most of previous researches were obtained from the cell medium of tumor cell lines, which cannot reflect the physiological state of primary cells in vivo. Isolation of native TEXs from human plasma with intact function is contributed to exploring the interaction between TEXs and recipient cells for understanding their true biological functions. RESULTS: We developed a strategy that involves both capture and release processes to obtain native TEXs from plasma of cancer patients. An MoS2-based immunomagnetic probe (Fe3O4@MoS2-Au-Aptamer, named as FMAA) with the advantages of high surface area, magnetic response and abundant affinity sites was designed and synthesized to capture TEXs through recognizing high-expression tumor-associated antigens of EpCAM. With the assistance of complementary sequences of EpCAM, TEXs were released with non-destruction and no residual labels. According to NTA analysis, 107-108 TEXs were recovered from per mL plasma of breast cancer patients. The interaction between native TEXs and normal epithelial cells confirms TEXs could induce significant activation of autophagy of recipient cells with co-culture for 12 h. Proteomics analysis demonstrated a total of 637 proteins inside epithelial cells had dynamic expression with the stimulation of TEXs and 5 proteins in the pathway of autophagy had elevated expression level. SIGNIFICANCE: This work not only obtains native TEXs from human plasma with non-destruction and no residual labels, but also explores the interaction between TEXs and recipient cells for understanding their true biological functions, which will accelerate the application of TEXs in the field of biomarkers and therapeutic drugs.

Autophagy activation is required for N6-methyladenosine modification to regulate ferroptosis in hepatocellular carcinoma.

BACKGROUND & AIMS: Although ferroptosis holds promise as a new strategy for treating hepatocellular carcinoma (HCC), there are several obstacles that need to be overcome. One major challenge is the lack of understanding about the mechanisms underlying ferroptosis. Additionally, while the m6A modification has been shown to regulate various forms of cell death, its role in regulating ferroptosis in HCC has been largely overlooked. Bridging this knowledge gap, our study aimed to elucidate the regulatory influence of m6A modification on HCC ferroptosis. MATERIALS: Dot blot and EpiQuik m6A RNA Methylation Quantitative kit detected changes in overall m6A modification level during ferroptosis in HCC. MeRIP-qPCR and RIP-qPCR identified that the m6A modification of ATG5 mRNA was significant changed. BALB/c nude mice were used to construct xenograft tumor models to verify the phenotypes upon YTHDC2 silencing. In addition, patient-derived organoid models were used to demonstrate that induction of ferroptosis was an effective strategy against HCC. RESULTS: Our study has shown that inducing ferroptosis is a promising strategy for combatting HCC. Specifically, we have found a significant correlation between ferroptosis and high levels of m6A modification in HCC. Notably, we discovered that the elevation of ATG5 mRNA m6A modification mediated by WTAP is dependent on the reading protein YTHDC2. Importantly, inhibition of either WTAP or YTHDC2 effectively prevented ferroptosis and suppressed HCC development in both in vitro and in vivo models. CONCLUSION: Our study revealed that WTAP upregulates ATG5 expression post-transcriptionally in an m6A-YTHDC2-dependent manner, thereby promoting the translation of ATG5 mRNA during ferroptosis in HCC. These findings have significant implications for the development of innovative and effective therapeutic approaches for HCC treatment.

Novel Three-Dimensional Hierarchical Porous Carbon Probe for the Discovery of N-Glycan Biomarkers and Early Hepatocellular Carcinoma Detection.

Due to the highly heterogeneous nature of hepatocellular carcinoma (HCC), the accurate diagnosis of HCC during the early phase of development is still a challenging task. Therefore, the further development of novel diagnostic methods by discovering new biomarkers is required to improve the rate of HCC diagnosis in the early phase. In this work, an oxygen-modified three-dimensional interconnected porous carbon probe is designed and fabricated to profile the differences of N-glycans in human serum from health controls (H) and patients with hepatic dysfunction (HD) and HCC for the discovery of new biomarkers with HCC development. Excitingly, we discovered that the expression levels of 12 serum N-glycans were gradually increased from H to patients with HD and eventually to patients with HCC. Moreover, two machine learning models established based on these 12 serum N-glycans reached a satisfactory accuracy for predicting HCC development where the receiver operating characteristic curve arrived above 0.95 for distinguishing healthy controls and patients with liver diseases (HD or HCC) and the ROC curve arrived at 0.85 for distinguishing HD and HCC. Our work not only developed a new method for the large-scale characterization of serum N-glycans but also provided valuable guidance for accurate and highly sensitive diagnosis of early liver cancer development in a non-invasive manner.

Targeting pancreatic stellate cells in chronic pancreatitis: Focus on therapeutic drugs and natural compounds.

Chronic pancreatitis (CP) is a precancerous illness linked to pancreatic ductal adenocarcinoma (PDAC), although the evolutionary mechanism is uncertain. CP is distinguished by severe fibrosis caused by the activation of pancreatic stellate cells (PSCs). The current clinical therapeutic protocol for CP lacks specific therapeutic medicines for the prevention and suppression of inflammation and fibrosis aggravating in CP. More research on specifically targeting PSCs would help facilitate the development of novel therapies for pancreatic fibrosis. Notably, using natural compounds from medicinal plants as new antifibrotic agents has become a focus of recent research and is widely employed as an alternative and complementary approach. Our goal was to shed light on the role of PSCs in the development of CP and provide a focused update on the new potential therapeutic strategies against PSCs in CP models. Future studies can refer to these possible strategies for drug design, bioavailability, pharmacokinetics, and other issues to obtain better clinical outcomes for treating CP.

Facile Preparation of Three-Dimensional Wafer with Interconnected Porous Structure for High-Performance Capture and Nondestructive Release of Circulating Tumor Cells.

Efficient isolation and downstream bioinformation analysis of circulating tumor cells (CTCs) in whole blood contribute to the early diagnosis of cancer and investigation of cancer metastasis. However, the separation and release of CTCs remain a great challenge due to the extreme rarity of CTCs and severe interference from other cells in complex clinical samples. Herein, we developed a low-cost and easy-to-fabricate aptamer-functionalized wafer with a three-dimensional (3D) interconnected porous structure by grafting polydopamine (PDA), poly(ethylene glycol) (PEG), and aptamer in sequence (Ni@PDA-PEG-Apt) for the capture and release of CTCs. The Ni@PDA-PEG-Apt wafer integrated the features of Ni foam with a 3D interconnected porous structure offering enough tunnels for cells to flow through and enhancing aptamer-cell contact frequency, the spacer PEG with flexible and high hydrophilic property increasing anti-interference ability and providing the wafer with more binding sites for aptamer, which result in an enhanced capture specificity and efficiency for CTCs. Because of these advantages, the Ni@PDA-PEG-Apt wafer achieved a high capture efficiency of 78.25%. The captured cancer cells were mildly released by endonuclease with up to 61.85% efficiency and good proliferation. Furthermore, tumor cells were injected into mice and experienced circulation in vivo. In blood samples after circulation, 65% of target tumor cells can be efficiently captured by the wafer, followed by released and recultured cells with high viability. Further downstream metabolomics analysis showed that target cancer cells remained with high biological activity and can be well separated from MCF-10A cells based on metabolic profiles by the PCA analysis, indicating the great potential of our strategy for further research on the progression of cancer metastasis. Notably, not only is the wafer cheap with a cost of only 3.58 U.S. dollars and easily prepared by environmental-friendly reagents but also the process of capturing and releasing tumor cells can be completed within an hour, which is beneficial for large-scale clinical use in the future.

Establishment of a dmp based maternal haploid induction system for polyploid Brassica napus and Nicotiana tabacum.

Doubled haploid (DH) technology is used to obtain homozygous lines in a single generation, a technique that significantly accelerates the crop breeding trajectory. Traditionally, in vitro culture is used to generate DHs, but this technique is limited by species and genotype recalcitrance. In vivo haploid induction (HI) through seed is widely and efficiently used in maize and was recently extended to several other crops. Here we show that in vivo HI can be triggered by mutation of DMP maternal haploid inducer genes in allopolyploid (allotetraploid) Brassica napus and Nicotiana tabacum. We developed a pipeline for selection of DMP orthologs for clustered regularly interspaced palindromic repeats mutagenesis and demonstrated average amphihaploid induction rates of 2.4% and 1.2% in multiple B. napus and N. tabacum genotypes, respectively. These results further confirmed the HI ability of DMP gene in polyploid dicot crops. The DMP-HI system offers a novel DH technology to facilitate breeding in these crops. The success of this approach and the conservation of DMP genes in dicots suggest the broad applicability of this technique in other dicot crops.

Asparaginyl endopeptidase protects against podocyte injury in diabetic nephropathy through cleaving cofilin-1.

Podocyte injury and loss are critical events in diabetic nephropathy (DN); however, the underlying molecular mechanisms remain unclear. Here, we demonstrate that asparaginyl endopeptidase (AEP) protects against podocyte injury through modulating the dynamics of the cytoskeleton. AEP was highly upregulated in diabetic glomeruli and hyperglycemic stimuli treated-podocytes; however, AEP gene knockout and its compound inhibitor treatment accelerated DN in streptozotocin-induced diabetic mice, whereas specific induction of AEP in glomerular cells attenuated podocyte injury and renal function deterioration. In vitro, elevated AEP was involved in actin cytoskeleton maintenance and anti-apoptosis effects. Mechanistically, we found that AEP directly cleaved the actin-binding protein cofilin-1 after the asparagine 138 (N138) site. The protein levels of endogenous cofilin-1 1-138 fragments were upregulated in diabetic podocytes, consistent with the changes in AEP levels. Importantly, we found that cofilin-1 1-138 fragments were remarkably unphosphorylated than full-length cofilin-1, indicating the enhanced cytoskeleton maintenance activity of cofilin-1 1-138. Then we validated cofilin-1 1-138 could rescue podocytes from cytoskeleton disarrangement and injury in diabetic conditions. Taken together, our data suggest a protective role of elevated AEP in podocyte injury during DN progression through cleaving cofilin-1 to maintain podocyte cytoskeleton dynamics and defend damage.

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study.

BACKGROUND: In the phase III open-label KEYNOTE-426 (NCT02853331) study, first-line pembrolizumab and axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC). KEYNOTE-426 evaluated patients enrolled from 25 sites in Japan. METHODS: Patients enrolled in Japan were included in this post hoc subgroup analysis. Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks plus oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS as assessed by blinded independent central review. Objective response rate (ORR) and safety were secondary endpoints. RESULTS: The Japanese subgroup comprised 94 patients (pembrolizumab-axitinib, n = 44; sunitinib, n = 50; 11% of the intent-to-treat population). Median time from randomization to data cutoff (January 6, 2020) was 29.5 months (range 24.6-37.3). Consistent with the intent-to-treat population, the OS, PFS, and ORR suggested improvement with pembrolizumab-axitinib versus sunitinib in the Japanese subgroup. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 70% of patients receiving pembrolizumab-axitinib versus 78% receiving sunitinib; 11 (25%) patients receiving pembrolizumab-axitinib and 13 (27%) patients receiving sunitinib discontinued the study medication due to AEs. TRAEs led to the discontinuation of pembrolizumab, axitinib, pembrolizumab-axitinib, or sunitinib in 32%, 34%, 14%, and 20%, respectively. No deaths from TRAEs occurred. CONCLUSIONS: Efficacy outcomes for the Japanese subgroup were consistent with those of the global population. Safety in Japanese patients was consistent with the results from the global population.

Development of site-specific antibody-conjugated immunoliposomes for sensitive detection of disease biomarkers.

Liposome-based immunoassay (LIA) is an attractive protocol for amplifying the detection signals because of the excellent ability of liposomes to encapsulate signal marker compounds. The antigen-binding activity of the conjugated antibodies on the liposomal surface is crucial for the specificity and sensitivity of LIA. We present here a general platform to ensure that antibodies can conjugate onto the surface of liposomes in a site-specific and oriented manner. A His-handle-modified antibody with Fc region-specific and covalent conjugation was first fabricated using a photoactivatable ZBpa-His tag that was engineered using the aminoacyl-tRNA synthetase/suppressor tRNA technique. Based on the high affinity between the His tag and divalent metal ions, the novel His-modified antibody was oriented onto the surface of nickel ion-modified liposomes encapsulating horseradish peroxidase. With the prostate-specific antigen as a model, the detection efficiency of the new immunoliposomes was evaluated by chemiluminescence immunoassay. The immunoliposomes exhibited a limit of detection of 0.2 pg mL-1, which was a six time improvement compared with that of the chemical-coupled antibody-liposome conjugates. Thus, the proposed immunoliposomes are expected to hold potential applications for the sensitive detection of various biomarkers in complicated serum samples.

Sulfur-Modified Oxygen Vacancies in Iron-Cobalt Oxide Nanosheets: Enabling Extremely High Activity of the Oxygen Evolution Reaction to Achieve the Industrial Water Splitting Benchmark.

The oxygen vacancies of defective iron-cobalt oxide (FeCoOx -Vo) nanosheets are modified by the homogeneously distributed sulfur (S) atoms. S atoms can not only effectively stabilize oxygen vacancies (Vo), but also form the Co-S coordination with Co active site in the Vo, which can modulate the electronic structure of the active site, enabling FeCoOx -Vo-S to exhibit much superior OER activity. FeCoOx -Vo-S exhibits a mass activity of 2440.0 A g-1 at 1.5 V vs. RHE in 1.0 m KOH, 25.4 times higher than that of RuO2 . The Tafel slope is as low as 21.0 mV dec-1 , indicative of its excellent charge transfer rate. When FeCoOx -Vo-S (anode catalyst) is paired with the defective CoP3 /Ni2 P (cathode catalyst) for overall water splitting, current densities of as high as 249.0 mA cm-2 and 406.0 mA cm-2 at a cell voltage of 2.0 V and 2.3 V, respectively, can be achieved.

Tuning the Product Selectivity of the Cu Hollow Fiber Gas Diffusion Electrode for Efficient CO2 Reduction to Formate by Controlled Surface Sn Electrodeposition.

The efficient CO2 electrochemical reduction reaction (CO2RR) relies not only on the development of selective/active catalysts but also on the advanced electrode configuration to solve the critical issue of poor CO2 mass transport and derived sluggish cathodic reaction kinetics. In this work, to achieve a favorable reaction rate and product selectivity, we designed and synthesized an asymmetric porous Cu hollow fiber gas diffusion electrode (HFGDE) with controlled Sn surface electrodeposition. The HFGDE derived from the optimal Sn electrodeposition condition exhibited a formate Faradaic efficiency (FE) of 78% and a current density of 88 mA cm-2 at -1.2 V versus reversible hydrogen electrode, which are more than 2 times higher than those from the pristine Cu HFGDE. The achieved performance outperformed most of the other Sn-based GDEs, indicating the creation of sufficient contact among CO2, electrolyte, and electrode catalyst through the design of the hollow fiber pore structure and catalytic active sites. The enhancement of formate production selectivity and the suppression of the hydrogen by-product were attributed to the optimized ratio of SnOx species on the electrode surface. The best performance was seen in the HFGDE with the highest Sn2+/Sn4+ (120 s deposition), likely due to the modulating effect of the Cu substrate via electron donation with Sn species. The selectivity control strategy developed in the asymmetric HFGDE provides an efficient and facile method to stimulate selective electrochemical reactions in which the gas-phase reactant with low solubility is involved.

Strontium-doped lanthanum iron nickelate oxide as highly efficient electrocatalysts for oxygen evolution reaction.

Pursuing efficient and low-cost catalysts for the sluggish oxygen evolution reaction (OER) is imperative for the large-scale deployment of promising electrochemical technologies such as water splitting and CO2 electrochemical reduction. The earth-abundant perovskite catalysts based on LaNiO3-δ show promise in OER catalysis because of their relatively low cost and their optimal electronic structure but suffer from low electrode-area normalized activity. In this work, we partially substituted La with Sr and Ni with Fe to enable a remarkably high OER activity with an ultra-low overpotential of 374 ±â€¯3 mV vs RHE at a current density of 10 mA cm-2 normalized by electrode geometric area. This performance even surpasses the performance of benchmark RuO2. Our results show that Sr could promote OER-active sites including Ni(III), O2-2/O-, and optimal Ni/Fe ratios, which significantly improve the surface intrinsic activity at the perovskite surface. Therefore, this work not only developed a highly efficient earth-abundant catalyst towards OER, but also demonstrated the effective modulation of catalyst surface interactions through A-site doping for perovskite oxides for key applications such as water splitting, CO2 electrochemical reduction and N2 electrochemical fixations.

Mangiferin improves hepatic damage-associated molecular patterns, lipid metabolic disorder and mitochondrial dysfunction in alcohol hepatitis rats.

This study was conducted to investigate the beneficial effects and possible mechanism of action of mangiferin (MF) in alcohol hepatitis (AH) rats. Building on our previous study, the damage-associated molecular patterns (DAMPs), lipid metabolic disorder and mitochondrial dysfunction were investigated. MF effectively regulated the abnormal liver function, the levels of alcohol, FFAs and metal elements in serum. More importantly, MF improved the expression levels of mRNA and protein of PPAR-γ, OPA-1, Cav-1, EB1, NF-κB p65, NLRP3, Cas-1 and IL-1ß, and decreased the positive protein expression rates of HSP90, HMGB1, SYK, CCL20, C-CAS-3, C-PARP and STARD1. Additionally, MF decreased the levels of fumarate, cAMP, xanthurenic acid and d-glucurone-6,3-lactone, and increased the levels of hippuric acid and phenylacetylglycine, and then adjusted the changes of phenylalanine metabolism, TCA cycle and ascorbate and aldarate metabolic pathways. The above results suggested that MF can effectively prevent AH by modulating specific AH-associated genes, potential biomarkers and metabolic pathways in AH rats, etc.

Ultrathin Iron-Cobalt Oxide Nanosheets with Abundant Oxygen Vacancies for the Oxygen Evolution Reaction.

Electrochemical water splitting is a promising method for storing light/electrical energy in the form of H2 fuel; however, it is limited by the sluggish anodic oxygen evolution reaction (OER). To improve the accessibility of H2 production, it is necessary to develop an efficient OER catalyst with large surface area, abundant active sites, and good stability, through a low-cost fabrication route. Herein, a facile solution reduction method using NaBH4 as a reductant is developed to prepare iron-cobalt oxide nanosheets (Fex Coy -ONSs) with a large specific surface area (up to 261.1 m2 g-1 ), ultrathin thickness (1.2 nm), and, importantly, abundant oxygen vacancies. The mass activity of Fe1 Co1 -ONS measured at an overpotential of 350 mV reaches up to 54.9 A g-1 , while its Tafel slope is 36.8 mV dec-1 ; both of which are superior to those of commercial RuO2 , crystalline Fe1 Co1 -ONP, and most reported OER catalysts. The excellent OER catalytic activity of Fe1 Co1 -ONS can be attributed to its specific structure, e.g., ultrathin nanosheets that could facilitate mass diffusion/transport of OH- ions and provide more active sites for OER catalysis, and oxygen vacancies that could improve electronic conductivity and facilitate adsorption of H2 O onto nearby Co3+ sites.

Low-Temperature Synthesis of Hierarchical Amorphous Basic Nickel Carbonate Particles for Water Oxidation Catalysis.

Amorphous nickel carbonate particles are catalysts for the oxygen evolution reaction (OER), which plays a critical role in the electrochemical splitting of water. The amorphous nickel carbonate particles can be prepared at a temperature as low as 60 °C by an evaporation-induced precipitation (EIP) method. The products feature hierarchical pore structures. The mass-normalized activity of the catalysts, measured at an overpotential of 0.35 V, was 55.1 A g(-1) , with a Tafel slope of only 60 mV dec(-1) . This catalytic activity is superior to the performance of crystalline NiOx particles and ß-Ni(OH)2 particles, and compares favorably to state-of-the-art RuO2 catalysts. The activity of the amorphous nickel carbonate is remarkably stable during a 10 000 s chronoamperometry test. Further optimization of synthesis parameters reveals that the amorphous structure can be tuned by adjusting the H2 O/Ni ratio in the precursor mixture. These results suggest the potential application of easily prepared hierarchical basic nickel carbonate particles as cheap and robust OER catalysts with high activity.