A case of polyglucosan body myopathy caused by an RBCK1 gene variant and literature review.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with Polyglucosan body myopathy 1 (PGBM1) caused by a novel compound heterozygous variant in the RBCK1 gene. METHODS: The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing. RESULTS: Through whole-exome sequencing, we found that there were c.919G>T; p. (Glu307*) and c.723_730dup; p. (Glu244fs) variants of the RBCK1 gene in the patient, inherited from his parents, constituting a compound heterozygous variation. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the two variants were rated as pathogenic, but there were no comparable cases. Previous literature reported 24 patients with RBCK1 gene variants, involving a total of 20 myocardial and 18 skeletal muscle cases. CONCLUSIONS: The patient was twice diagnosed with cardiac insufficiency, neglecting the usual manifestations of muscle weakness, resulting in misdiagnosis. Later, novel variants in the RBCK1 gene were discovered through whole-exome sequencing, and symptomatic treatment was given after diagnosis. The importance of whole-exome sequencing technology in disease diagnosis and genetic counseling was emphasized.

Controlling Product Distribution of Polyethylene Hydrogenolysis Using Bimetallic RuM3 (M = Fe, Co, Ni) Catalysts.

Plastic hydrogenolysis is an attractive approach for producing value-added chemicals due to its mild reaction conditions, but controlling product distribution is challenging due to the formation of undesired CH4. This work reports several bimetallic RuM3/CeO2 (M = Fe, Co, Ni) catalysts that shift the product of low-density polyethylene hydrogenolysis toward longer-chain hydrocarbons. These catalysts were characterized by using X-ray absorption fine structure spectroscopy, electron microscopy imaging, and H2 temperature-programmed reduction. The combined catalytic evaluation and characterization results revealed that the product distribution was regulated by the formation of bimetallic alloys. A model compound, n-hexadecane, was selected to further understand the differences in hydrogenolysis over the Ru-based catalysts. Although a longer reaction time shifted the product toward smaller molecules, the bimetallic (RuCo3/CeO2) catalyst limited the further conversion of C2-C5 into CH4. This work highlights the role of bimetallic alloys in tailoring the interaction with hydrocarbons, thereby controlling the product distribution of polymer hydrogenolysis.

A novel variant of DNM1L expanding the clinical phenotypic spectrum: a case report and literature review.

BACKGROUND: Mitochondrial diseases are heterogeneous in terms of clinical manifestations and genetic characteristics. The dynamin 1-like gene (DNM1L) encodes dynamin-related protein 1 (DRP1), a member of the GTPases dynamin superfamily responsible for mitochondrial and peroxisomal fission. DNM1L variants can lead to mitochondrial fission dysfunction. CASE PRESENTATION: Herein, we report a distinctive clinical phenotype associated with a novel variant of DNM1L and review the relevant literature. A 5-year-old girl presented with paroxysmal hemiplegia, astigmatism, and strabismus. Levocarnitine and coenzyme Q10 supplement showed good efficacy. Based on the patient's clinical data, trio whole-exome sequencing (trio-WES) and mtDNA sequencing were performed to identify the potential causative genes, and Sanger sequencing was used to validate the specific variation in the proband and her family members. The results showed a novel de novo heterozygous nonsense variant in exon 20 of the DNM1L gene, c.2161C>T, p.Gln721Ter, which is predicted to be a pathogenic variant according to the ACMG guidelines. The proband has a previously undescribed clinical manifestation, namely hemiparesis, which may be an additional feature of the growing phenotypic spectrum of DNM1L-related diseases. CONCLUSION: Our findings elucidate a novel variant in DNM1L-related disease and reveal an expanding phenotypic spectrum associated with DNM1L variants. This report highlights the necessity of next generation sequencing for early diagnosis of patients, and that further clinical phenotypic and genotypic analysis may help to improve the understanding of DNM1L-related diseases.

Bioinspired Self-Assembly of Metalloporphyrins and Polyelectrolytes into Hierarchical Supramolecular Nanostructures for Enhanced Photocatalytic H2 Production in Water.

Polypeptides, as natural polyelectrolytes, are assembled into tailored proteins to integrate chromophores and catalytic sites for photosynthesis. Mimicking nature to create the water-soluble nanoassemblies from synthetic polyelectrolytes and photocatalytic molecular species for artificial photosynthesis is still rare. Here, we report the enhancement of the full-spectrum solar-light-driven H2 production within a supramolecular system built by the co-assembly of anionic metalloporphyrins with cationic polyelectrolytes in water. This supramolecular photocatalytic system achieves a H2 production rate of 793 and 685 µmol h-1 g-1 over 24 h with a combination of Mg or Zn porphyrin as photosensitizers and Cu porphyrin as a catalyst, which is more than 23 times higher than that of free molecular controls. With a photosensitizer to catalyst ratio of 10000 : 1, the highest H2 production rate of >51,700 µmol h-1 g-1 with a turnover number (TON) of >1,290 per molecular catalyst was achieved over 24 h irradiation. The hierarchical self-assembly not only enhances photostability through forming ordered stackings of the metalloporphyrins but also facilitates both energy and electron transfer from antenna molecules to catalysts, and therefore promotes the photocatalysis. This study provides structural and mechanistic insights into the self-assembly enhanced photostability and catalytic performance of supramolecular photocatalytic systems.

Case report of a child with long QT syndrome type 14 caused by CALM1 gene mutation and literature review.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with long QT syndrome type 14 (long QT syndrome-14, LQT14, OMIM # 616247) caused by a de novo CALM1 mutation. METHODS: The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome gene sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing. RESULTS: A 5-year and 9-month-old girl was admitted to the hospital due to a syncopal episode. During the attack, the main symptoms were loss of consciousness, cyanosis of the face and lips, and weakness of limbs. The child had multiple seizures in the past, all of which occurred after emotional excitement and activity. She was diagnosed with epilepsy for more than 3 years, but the effect of antiepileptic treatment was not satisfactory. The electrocardiogram was normal in the past. A month ago, convulsions occurred again after exercise, and the electrocardiogram showed QTc 496 ms. The treadmill test showed a significant prolongation of QTc after exercise, and the genetic results suggested a new heterozygous variant of CALM1, c.395A>G; p. (Asp132Gly). Consequently, she was diagnosed with LQT14 and treated with propranolol. During a follow-up of 15 months, there were no seizures or syncope. CONCLUSIONS: This patient had multiple episodes of convulsions or syncope after emotional stimulation or activity, with intermittent prolongation of the QTc on routine ECG, marked prolongation of the QTc after exercise, and T-wave alternans, which differed from the LQT14 phenotype caused by the previous CALM1 mutation.

Bimetallic-Derived Catalytic Structures for CO2-Assisted Ethane Activation.

ConspectusIn recent years, the simultaneous upgrading of CO2 and ethane has emerged as a promising approach for generating valuable gaseous (CO, H2, and ethylene) and liquid (aromatics and C3 oxygenates) chemicals from the greenhouse gas CO2 and large-reserved shale gas. The key challenges for controlling product selectivity lie in the selective C-H and C-C bond cleavage of ethane with the assistance of CO2. Bimetallic-derived catalysts likely undergo alloying or oxygen-induced segregation under reaction conditions, thus providing diverse types of interfacial sites, e.g., metal/support (M/M'Ox) interface and metal oxide/metal (M'Ox/M) inverse interface, that are beneficial for selective CO2-assisted ethane upgrading. The alloying extent can be initially predicted by cohesive energy and atomic radius (or Wigner-Seitz radius), while the preference for segregation to form the on-top suboxide can be approximated using the work function, electronegativity, and binding strength of adsorbed oxygen. Furthermore, bimetallic-derived catalysts are typically supported on high surface area oxides. Modifying the reducibility and acidity/basicity of the oxide supports and introducing surface defects facilitate CO2 activation and oxygen supplies for ethane activation.Using in situ synchrotron characterization and density functional theory (DFT) calculations, we found that the electronic properties of oxygen species influence the selective cleavage of C-H/C-C bonds in ethane, with electron-deficient oxygen over the metal (or alloy) surface promoting nonselective bond scission to produce syngas and electron-enriched oxygen over the metal oxide/metal interface enhancing selective C-H scission to yield ethylene. We further demonstrate that the preferred structures of the catalyst surfaces, either alloy surfaces or metal oxide/metal inverse interfaces, can be controlled through the appropriate choice of metal combinations and their atomic ratios. Through a comprehensive comparison of experimental results and DFT calculations, the selectivity of C-C/C-H bond scission is correlated with the thermodynamically favorable bimetallic-derived structures (i.e., alloy surfaces or metal oxide/metal inverse interfaces) under reaction conditions over a wide range of bimetallic catalysts. These findings not only offer structural and mechanistic insights into bimetallic-derived catalysts but also provide design principles for selective catalysts for CO2-assisted activation of ethane and other light alkanes. This Account concludes by discussing challenges and opportunities in designing advanced bimetallic-derived catalysts, incorporating new reaction chemistries for other products, employing precise synthesis strategies for well-defined structures with optimized site densities, and leveraging time/spatial/energy-resolved in situ spectroscopy/scattering/microscopy techniques for comprehensive structural analysis. The research methodologies established here are helpful for the investigation of dynamic alloy and interfacial structures and should inspire more efforts toward the simultaneous upgrading of CO2 and shale gas.

[Clinical and genetic analysis of five children with Catecholaminergic polymorphic ventricular tachycardia due to variants of RYR2 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT). METHODS: Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with ß-blocker propranolol and followed up. RESULTS: All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up. CONCLUSION: Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.

CO electroreduction on single-atom copper.

Electroreduction of carbon dioxide (CO2) or carbon monoxide (CO) toward C2+ hydrocarbons such as ethylene, ethanol, acetate and propanol represents a promising approach toward carbon-negative electrosynthesis of chemicals. Fundamental understanding of the carbon─carbon (C-C) coupling mechanisms in these electrocatalytic processes is the key to the design and development of electrochemical systems at high energy and carbon conversion efficiencies. Here, we report the investigation of CO electreduction on single-atom copper (Cu) electrocatalysts. Atomically dispersed Cu is coordinated on a carbon nitride substrate to form high-density copper─nitrogen moieties. Chemisorption, electrocatalytic, and computational studies are combined to probe the catalytic mechanisms. Unlike the Langmuir-Hinshelwood mechanism known for copper metal surfaces, the confinement of CO adsorption on the single-copper-atom sites enables an Eley-Rideal type of C-C coupling between adsorbed (*CO) and gaseous [CO(g)] carbon moxide molecules. The isolated Cu sites also selectively stabilize the key reaction intermediates determining the bifurcation of reaction pathways toward different C2+ products.

[Analysis of clinical characteristics and ACADM gene variants in four children with Medium chain acyl-CoA dehydrogenase deficiency].

OBJECTIVE: To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). METHODS: Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES). RESULTS: All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant. CONCLUSION: The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.

[Clinical characteristics and genetic analysis of a child with Galactosemia due to compound heterozygous variants of GALT gene].

OBJECTIVE: To explore the clinical features and genetic basis of a child with Galactosemia. METHODS: A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing. RESULTS: Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR). CONCLUSION: Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.

Identification of monoclonal antibody targeting epitope on p72 trimeric spike of African swine fever virus.

African swine fever virus (ASFV) is highly contagious and can cause lethal disease in pigs. ASFV p72 protein is a major capsid protein that presents as trimer in the virion. Epitopes on the surface of p72 trimer are considered as protective antigens. In this study, recombinant p72 protein and p72-baculovirus were constructed and obtained. Three monoclonal antibodies (mAbs) specific to ASFV p72 protein, designated as 1A3, 2B5 and 4A5, were generated. Among them, 4A5 showed strong reactivity with ASFV infected cells. Subsequently, the epitope recognized by 4A5 was mapped and identified using a series of overlapping peptides generated from p72 protein. IFA and western blot analyses showed that 4A5 recognized the linear epitope of p72 monomer located between amino acids 245-285 and recognized the conformational epitope located at the surface and top of the p72 trimer. These findings will enrich our knowledge regarding the epitope on p72 protein and provide valuable information for further characterization of the antigenicity and molecular functions of p72 protein.

African swine fever virus I73R is a critical virulence-related gene: A potential target for attenuation.

African swine fever virus (ASFV) is a large, double-stranded DNA virus that causes a fatal disease in pigs, posing a threat to the global pig industry. Whereas some ASFV proteins have been found to play important roles in ASFV-host interaction, the functional roles of many proteins are still largely unknown. In this study, we identified I73R, an early viral gene in the replication cycle of ASFV, as a key virulence factor. Our findings demonstrate that pI73R suppresses the host innate immune response by broadly inhibiting the synthesis of host proteins, including antiviral proteins. Crystallization and structural characterization results suggest that pI73R is a nucleic-acid-binding protein containing a Zα domain. It localizes in the nucleus and inhibits host protein synthesis by suppressing the nuclear export of cellular messenger RNA (mRNAs). While pI73R promotes viral replication, the deletion of the gene showed that it is a nonessential gene for virus replication. In vivo safety and immunogenicity evaluation results demonstrate that the deletion mutant ASFV-GZΔI73R is completely nonpathogenic and provides effective protection to pigs against wild-type ASFV. These results reveal I73R as a virulence-related gene critical for ASFV pathogenesis and suggest that it is a potential target for virus attenuation. Accordingly, the deletion mutant ASFV-GZΔI73R can be a potent live-attenuated vaccine candidate.

Utilizing CO2 as a Reactant for C3 Oxygenate Production via Tandem Reactions.

One possible solution to closing the loop on carbon emissions is using CO2 as the carbon source to generate high-value, multicarbon products. In this Perspective, we describe four tandem reaction strategies for converting CO2 into C3 oxygenated hydrocarbon products (i.e., propanal and 1-propanol), using either ethane or water as the hydrogen source: (1) thermocatalytic CO2-assisted dehydrogenation and reforming of ethane to ethylene, CO, and H2, followed by heterogeneous hydroformylation, (2) one-pot conversion of CO2 and ethane using plasma-activated reactions in combination with thermocatalysis, (3) electrochemical CO2 reduction to ethylene, CO, and H2, followed by thermocatalytic hydroformylation, and (4) electrochemical CO2 reduction to CO, followed by electrochemical CO reduction to C3 oxygenates. We discuss the proof-of-concept results and key challenges for each tandem scheme, and we conduct a comparative analysis of the energy costs and prospects for net CO2 reduction. The use of tandem reaction systems can provide an alternative approach to traditional catalytic processes, and these concepts can be further extended to other chemical reactions and products, thereby opening new opportunities for innovative CO2 utilization technologies.

A de novo low-frequency mosaic variant of KIF1A causes hereditary spastic paraplegia: A literature review.

OBJECTIVE: The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations. METHODS: High-throughput whole-exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing. Deep high-throughput sequencing was performed on subjects with suspected mosaic variants. The previously reported pathogenic variant loci of the KIF1A gene with complete data were collected, and the clinical manifestations and characteristics of the pathogenic KIF1A gene variant were analyzed. RESULTS: A pathogenic heterozygous variant located in the neck coil of the KIF1A gene (c.1139G>C, p.Arg380Pro) was identified in the proband and four additional members of the family. It was derived from the de novo low-frequency somatic-gonadal mosaicism of the proband's grandmother and had a rate of 10.95%. INTERPRETATION: This study helps us to better understand the pathogenic mode and characteristics of mosaic variants, and to understand the location and clinical characteristics of pathogenic variants in KIF1A.

Atomistic Origins of Reversible Noncatalytic Gas-Solid Interfacial Reactions.

Noncatalytic gas-solid reactions are a large group of heterogeneous reactions that are usually assumed to occur irreversibly because of the strong driving force to favor the forward direction toward the product formation. Using the example of Ni oxidation into NiO with CO2, herein, we demonstrate the existence of the reverse element that results in the NiO reduction from the countering effect of the gaseous product of CO. Using in situ electron microscopy observations and atomistic modeling, we show that the oxidation process occurs via preferential CO2 adsorption along step edges that results in step-flow growth of NiO layers, and the presence of Ni atoms on the flat NiO surface promotes the nucleation of NiO layers. Simultaneously, the NiO reduction happens via preferential step-edge adsorption of CO that leads to the receding motion of atomic steps, and the presence of Ni vacancies in the NiO surface facilitates the CO-adsorption-induced surface pitting. Temperature and CO2 pressure effect maps are constructed to illustrate the spatiotemporal dynamics of the competing NiO redox reactions. These results demonstrate the rich gas-solid surface reaction dynamics induced by the coexisting forward and reverse reaction elements and have practical applicability in manipulating gas-solid reactions via controlling the gas environment or atomic structure of the solid surface to steer the reaction toward the desired direction.

Arrested Phase Separation Enables High-Performance Keratoprostheses.

Corneal transplantation is impeded by donor shortages, immune rejection, and ethical reservations. Pre-made cornea prostheses (keratoprostheses) offer a proven option to alleviate these issues. Ideal keratoprostheses must possess optical clarity and mechanical robustness, but also high permeability, processability, and recyclability. Here, it is shown that rationally controlling the extent of arrested phase separation can lead to optimized multiscale structure that reconciles permeability and transparency, a previously conflicting goal by common pore-forming strategies. The process is simply accomplished by hydrothermally treating a dense and transparent hydrophobic association hydrogel. The examination of multiscale structure evolution during hydrothermal treatment reveals that the phase separation with upper miscibility gap evolves to confer time-dependent pore growth due to slow dynamics of polymer-rich phase which is close to vitrification. Such a process can render a combination of multiple desired properties that equal or surpass those of the state-of-the-art keratoprostheses. In vivo tests confirm that the keratoprosthesis can effectively repair corneal perforation and restore a transparent cornea with treatment outcomes akin to that of allo-keratoplasty. The keratoprosthesis is easy to access and convenient to carry, and thus would be an effective temporary substitute for a corneal allograft in emergency conditions.

Tuning the nanostructure and molecular orientation of high molecular weight diketopyrrolopyrrole-based polymers for high-performance field-effect transistors.

As a versatile class of semiconductors, diketopyrrolopyrrole (DPP)-based conjugated polymers are well suited for applications of next-generation plastic electronics because of their excellent and tunable optoelectronic properties via a rational design of chemical structures. However, it remains a challenge to unravel and eventually influence the correlation between their solution-state aggregation and solid-state microstructure. In this contribution, the solution-state aggregation of high molecular weight PDPP3T is effectively enhanced by solvent selectivity, and a fibril-like nanostructure with short-range and long-range order is generated and tuned in thin films. The predominant role of solvent quality on polymer packing orientation is revealed, with an orientational transition from a face-on to an edge-on texture for the same PDPP3T. The resultant edge-on arranged films lead to a significant improvement in charge transport in transistors, and the field-effect hole mobility reaches 2.12 cm2 V-1 s-1 with a drain current on/off ratio of up to 108. Our findings offer a new strategy for enhancing the device performance of polymer electronic devices.

Evaluation of an I177L gene-based five-gene-deleted African swine fever virus as a live attenuated vaccine in pigs.

African swine fever (ASF) is a highly contagious disease of domestic and wild pigs caused by the African swine fever virus (ASFV). The current research on ASF vaccines focuses on the development of naturally attenuated, isolated, or genetically engineered live viruses that have been demonstrated to produce reliable immunity. As a result, a genetically engineered virus containing five genes deletion was synthesized based on ASFV Chinese strain GZ201801, named ASFV-GZΔI177LΔCD2vΔMGF. The five-gene-deleted ASFV was safe and fully attenuated in pigs and provides reliable protection against the parental ASFV strain challenge. This indicates that the five-gene-deleted ASFV is a potential candidate for a live attenuated vaccine that could control the spread of ASFV.

Hybrid Catalyst Coupling Single-Atom Ni and Nanoscale Cu for Efficient CO2 Electroreduction to Ethylene.

A hybrid catalyst with integrated single-atom Ni and nanoscale Cu catalytic components is reported to enhance the C-C coupling and ethylene (C2H4) production efficiency in the electrocatalytic CO2 reduction reaction (eCO2RR). The single-atom Ni anchored on high-surface-area ordered mesoporous carbon enables high-rate and selective conversion of CO2 to CO in a wide potential range, which complements the subsequent CO enrichment on Cu nanowires (NWs) for the C-C coupling to C2H4. In situ surface-enhanced infrared absorption spectroscopy (SEIRAS) confirms the substantially improved CO enrichment on Cu, once the incorporation of single-atom Ni occurs. Also, in situ X-ray absorption near-edge structure (XANES) demonstrates the structural stability of the hybrid catalyst during eCO2RR. By modulating hybrid compositions, the optimized catalyst shows 66% Faradaic efficiency (FE) in an alkaline flow cell with over 100 mA·cm-2 at -0.5 V versus reversible hydrogen electrode, leading to a five-order enhancement in C2H4 selectivity compared with single-component Cu NWs.