A truncated B-box zinc finger transcription factor confers drought sensitivity in modern cultivated tomatoes.

Enhancing drought tolerance in crops and understanding the underlying mechanisms have been subject of intense research. The precise function and molecular mechanisms of B-box zinc finger proteins (BBX) remain elusive. Here, we report a natural allele of BBX18 (BBX18TT) that encodes a C-terminal truncated protein. While most wild tomato germplasms contain the BBX18CC allele and show more drought tolerant, modern cultivated tomatoes mostly carry BBX18TT allele and are more drought sensitive. Knockout of BBX18 leads to improved drought tolerance in transgenic plants of cultivated tomato. Ascorbate peroxidase 1 (APX1) is identified as a BBX18-interacting protein that acts as a positive regulator of drought resistance in tomato. Chromatin immunoprecipitation sequencing analyses reveal that BBX18 binds to a unique cis-acting element of the APX1 promoter and represses its gene expression. This study provides insights into the molecular mechanism underlying drought resistance mediated by the BBX18-APX1 module in plants.

The tomato WRKY-B transcription factor modulates lateral branching by targeting BLIND, PIN4, and IAA15.

Lateral branching is a crucial agronomic trait that impacts crop yield. In tomato ( Solanum lycopersicum ), excessive lateral branching is unfavorable and results in substantial labor and management costs. Therefore, optimizing lateral branching is a primary objective in tomato breeding. Although many genes related to lateral branching have been reported in tomato, the molecular mechanism underlying their network remains elusive. In this study, we found that the expression profile of a WRKY gene, WRKY-B (for WRKY-BRANCING), was associated with the auxin-dependent axillary bud development process. Wrky-b mutants generated by the CRISPR/Cas9 editing system presented fewer lateral branches, while WRKY-B overexpression lines presented more lateral branches than did wild-type plants. Furthermore, WRKY-B can directly target the well-known branching gene BLIND (BL) and the auxin efflux carrier gene PIN4 to activate their expression. Both the bl and pin4 mutants exhibited reduced lateral branching, similar to the wrky-b mutant. The IAA contents in the axillary buds of the wrky-b, bl, and pin4 mutant plants were significantly higher than those in the wild-type plants. In addition, WRKY-B can also directly target the AUX/IAA gene IAA15 and repress its expression. In summary, WRKY-B works upstream of BL, PIN4, and IAA15 to regulate the development of lateral branches in tomato.

Delivery approaches of immunomodulatory nucleic acids for cancer therapy.

Messenger RNA (mRNA) vaccines have made remarkable public health contributions during the pandemic and initiated a new era for nucleic acid-based therapeutics. With the unique strength of nucleic acids, including not only mRNA but also DNA, microRNA, small interfering RNA (siRNA), and other nucleic acids, either in tuning off genes or introducing function, nucleic acid therapeutics have been regarded as potential candidates for the treatment of many different diseases, especially for the immunomodulation in cancer. However, the scope of the applications was limited by the challenges in delivery due to intrinsic properties of nucleic acids including low stability, immunogenicity, and toxicity. Bioengineering approaches toward efficient and targeted delivery of therapeutic nucleic acids have gained momentum in clinical applications in the past few decades. Recent advances in the biotechnological approaches for the delivery of mRNA, siRNA, and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas for immunomodulatory are promising alternatives in designing future cancer immunotherapy.

Superassembled Mesoporous Carbon-Fe2O3 Heterochannels for Photothermal-Enhanced Hyaluronidase Sensing.

Developing an activity detection platform for hyaluronidase (HAase) is crucial for diagnosing and treating cancer. However, traditional detection of HAase is based on changes in the flow rate caused by viscosity or requires complex modifications and processing, which limits the detection accuracy and sensitivity. Herein, hyaluronic acid (HA)-modified mesoporous-based heterochannels (mesoporous carbon-doped γ-Fe2O3 nanoparticles/anodized aluminum oxide, MC-γ-Fe2O3/AAO) featuring ordered 3D transport frameworks and a photothermal property were developed for high performance HAase detection. The HA molecules on the surface of the mesoporous layer provide abundant active sites for HAase detection. An improved ionic current was realized after enzymatic hydrolysis reactions between HA and HAase due to enhanced surface charges and more hydrophilicity, leading to highly sensitive and accurate HAase detection. Notably, the detection performance can be further upgraded with the assistance of the photothermal property of γ-Fe2O3. An amplified detection current signal was achieved owing to a synergistic effect between ion currents and photoresponsive currents. A wide linear detection range from 1 to 50 U/mL and a low detection limit of 0.348 U/mL were obtained, achieving a 2% improvement under illumination. Importantly, the heterochannels have also been successfully applied for HAase detection in fetal bovine serum samples, manifesting considerable application prospects. This work provides a new strategy in constructing photoresponsive nanochannels with a photothermal property for a highly efficient biosensing platform.

Nurse burnout: deep connections and solutions revealed by network analysis.

BACKGROUND: Burnout is very important to nurses' physical and mental health and career development. Current approaches to assessing nurse burnout tend to use a total score modeling paradigm to explore the impact of external factors on burnout. The purpose of this study is to delve into the item-level relationship between nurse burnout and its influencing factors at both the social and psychological levels using a network analysis approach. METHODS: This study was conducted in June 2023 and 1,005 nurses from 4 hospitals out of 8 tertiary care hospitals in Harbin were selected to participate in this study using whole cluster sampling method. Measurements included a general demographic questionnaire, Trait coping styles questionnaire, Organizational commitment questionnaire, Work-family conflict scale, Transformational leadership questionnaire, and Maslach Burnout Inventory-General Survey. RESULTS: Our results suggest that "C1 Time-Based work interference with family" showed the strongest centrality and bridging in the overall network. This finding underscores its centrality to burnout. Other strongest bridge symptoms included "E2 Reduced personal accomplishment" and "A1 Positive coping styles" indicating their strongest connections to other clusters. CONCLUSIONS: Nurse administrators should be encouraged to pay more attention to nurses' work situations and family distress, and to help nurses in a flexible way.

Relationship between family function and anxiety among nurses during the COVID-19 pandemic: a mediating role of expressive suppression.

BACKGROUND: The aims of the present study were to investigate the incidence of nurses who suffered anxiety during the COVID-19 pandemic and to explore how expressive suppression influences the relationship between family function and anxiety. METHODS: This study used cross-sectional research and simple random sampling. A total of 300 questionnaires were distributed and 254 questionnaires were qualified after invalid questionnaires were proposed, thus a total of 254 female nurses from a tertiary hospital were included in this study. The measurement included General demographic questionnaires, the Self-Scale Anxiety, Scale (SAS), Emotion Regulation Strategies Questionnaire (ERQ), and Family Function Assessment (FAD). T-test, nonparametric Wilcoxon or Kruskal-Wallis test, χ2 test, Pearson or Spearman correlation analysis, multiple stepwise regression and bootstrap methods was performed to analyze the data. RESULTS: In this study, 22.4% of the nurses exhibited anxiety symptoms, with 17.7% eliciting mild anxiety symptoms, 4.3% showing moderate anxiety symptoms and 0.4% with severe anxiety symptoms. Family function and expressive suppression were positively associated with anxiety severity. And family function influenced anxiety among nurses via direct and indirect (Expressive suppression -mediated) pathways. CONCLUSIONS: Expressive suppression partially mediated the influence of family function on anxiety symptom. To this end, nurse administrators should establish a robust mental health support system encompassing psychological counseling and emotional support groups. Furthermore, nurse administrators should consistently inquire about nurses' family situations, encourage nurses to articulate their emotions and needs candidly, both within the domestic sphere and the workplace, while refraining from excessive self-repression.

Bacterial c-di-GMP triggers metamorphosis of mussel larvae through a STING receptor.

Bacteria induced metamorphosis observed in nearly all marine invertebrates. However, the mechanism of bacteria regulating the larvae-juvenile metamorphosis remains unknown. Here, we test the hypothesis that c-di-GMP, a ubiquitous bacterial second-messenger molecule, directly triggers the mollusc Mytilus coruscus larval metamorphosis via the stimulator of interferon genes (STING) receptor. We determined that the deletion of c-di-GMP synthesis genes resulted in reduced c-di-GMP levels and biofilm-inducing activity on larval metamorphosis, accompanied by alterations in extracellular polymeric substances. Additionally, c-di-GMP extracted from tested varying marine bacteria all exhibited inducing activity on larval metamorphosis. Simultaneously, through pharmacological and molecular experiments, we demonstrated that M. coruscus STING (McSTING) participates in larval metamorphosis by binding with c-di-GMP. Our findings reveal that new role of bacterial c-di-GMP that triggers mussel larval metamorphosis transition, and extend knowledge in the interaction of bacteria and host development in marine ecosystems.

Morphology Regulation of UiO-66-2I Supporting Systematic Investigations of Shape-Dependent Catalytic Activity for Degradation of an Organophosphate Nerve Agent Simulant.

Phosphonate-based nerve agents, as a kind of deadly chemical warfare agent, are a persistent and evolving threat to humanity. Zirconium-based metal-organic frameworks (Zr-MOFs) are a kind of highly porous crystalline material that includes Zr-OH-Zr sites and imitates the active sites of the phosphotriesterase enzyme, representing significant potential for the adsorption and catalytic hydrolysis of phosphonate-based nerve agents. In this work, we present a new Zr-MOF, UiO-66-2I, which attaches two iodine atoms in the micropore of the MOF and exhibits excellent catalytic activity on the degradation of a nerve agent simulant, dimethyl 4-nitrophenyl phosphate (DMNP), as the result of the formation of halogen bonds between the phosphate ester bonds and iodine groups. Furthermore, various morphologies of UiO-66-2I, such as blocky-shaped nanoparticles (NPs), two-dimensional (2D) nanosheets, hexahedral NPs, stick-like NPs, colloidal microspheres, and colloidal NPs, have been obtained by adding acetic acid (AA), formic acid (FA), propionic acid (PA), valeric acid (VA), benzoic acid (BA), and trifluoroacetic acid (TFA) as modulators, respectively, and show different catalytic hydrolysis activities. Specifically, the catalytic activities follow the trend UiO-66-2I-FA (t1/2 = 1 min) > UiO-66-2I-AA-NP (t1/2 = 4 min) ≈ UiO-66-2I-VA (t1/2 = 4 min) > UiO-66-2I-BA (t1/2 = 5 min) > UiO-66-2I-PA (t1/2 = 15 min) > UiO-66-2I-TFA (t1/2 = 18 min). The experimental results show that the catalytic hydrolysis activity of Zr-MOF is regulated by the crystallinity, defect quantity, morphologies, and hydrophilicity of these samples, which synergistically affect the accessibility of catalytic sites and the diffusion of phosphate in the pores of Zr-MOFs.

Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 µM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Mapping the neural mechanism that distinguishes between holistic thinking and analytic thinking.

Holistic and analytic thinking are two distinct modes of thinking used to interpret the world with relative preferences varying across cultures. While most research on these thinking styles has focused on behavioral and cognitive aspects, a few studies have utilized functional magnetic resonance imaging (fMRI) to explore the correlations between brain metrics and self-reported scale scores. Other fMRI studies used single holistic and analytic thinking tasks. As a single task may involve processing in spurious low-level regions, we used two different holistic and analytic thinking tasks, namely the frame-line task and the triad task, to seek convergent brain regions to distinguish holistic and analytic thinking using multivariate pattern analysis (MVPA). Results showed that brain regions fundamental to distinguish holistic and analytic thinking include the bilateral frontal lobes, bilateral parietal lobes, bilateral precentral and postcentral gyrus, bilateral supplementary motor areas, bilateral fusiform, bilateral insula, bilateral angular gyrus, left cuneus, and precuneus, left olfactory cortex, cingulate gyrus, right caudate and putamen. Our study maps brain regions that distinguish between holistic and analytic thinking and provides a new approach to explore the neural representation of cultural constructs. We provide initial evidence connecting culture-related brain regions with language function to explain the origins of cultural differences in cognitive styles.

Leukotriene B4: A potential mediator and biomarker for cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of long-term graft failure and mortality after heart transplantation. Effective preventive and treatment options are not available to date, largely because underlying mechanisms remain poorly understood. We studied the potential role of leukotriene B4 (LTB4), an inflammatory lipid mediator, in the development of CAV. METHODS: We used an established preclinical rat CAV model to study the role of LTB4 in CAV. We performed syngeneic and allogeneic orthotopic aortic transplantation, after which neointimal proliferation was quantified. Animals were then treated with Bestatin, an inhibitor of LTB4 synthesis, or vehicle control for 30 days post-transplant, and evidence of graft CAV was determined by histology. We also measured serial LTB4 levels in a cohort of 28 human heart transplant recipients with CAV, 17 matched transplant controls without CAV, and 20 healthy nontransplant controls. RESULTS: We showed that infiltration of the arterial wall with macrophages leads to neointimal thickening and a rise in serum LTB4 levels in our rat model of CAV. Inhibition of LTB4 production with the drug Bestatin prevents development of neointimal hyperplasia, suggesting that Bestatin may be effective therapy for CAV prevention. In a parallel study of heart transplant recipients, we found nonsignificantly elevated plasma LTB4 levels in patients with CAV, compared to patients without CAV and healthy, nontransplant controls. CONCLUSIONS: This study provides key evidence supporting the role of the inflammatory cytokine LTB4 as an important mediator of CAV development and provides preliminary data suggesting the clinical benefit of Bestatin for CAV prevention.

Bacterial c-di-GMP signaling gene affects mussel larval metamorphosis through outer membrane vesicles and lipopolysaccharides.

Biofilms serve as crucial cues for settlement and metamorphosis in marine invertebrates. Within bacterial systems, c-di-GMP functions as a pivotal signaling molecule regulating both biofilm formation and dispersion. However, the molecular mechanism of how c-di-GMP modulates biofilm-induced larval metamorphosis remains elusive. Our study reveals that the deletion of a c-di-GMP related gene in Pseudoalteromonas marina led to an increase in the level of bacterial c-di-GMP by knockout technique, and the mutant strain had an enhanced ability to produce more outer membrane vesicles (OMVs) and lipopolysaccharides (LPS). The mutant biofilms had higher induction activity for larval metamorphosis in mussels Mytilus coruscus, and OMVs play a major role in the induction activity. We further explored the function of LPS in OMVs. Extracted LPS induced high larval metamorphosis rate, and LPS content were subject to c-di-GMP and LPS-biosynthesis gene. Thus, we postulate that the impact of c-di-GMP on biofilm-induced metamorphosis is mediated through OMVs and LPS.

Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.

Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M-/-, CIITA-/-, CD47+), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.

Color components determination and full-length comparative transcriptomic analyses reveal the potential mechanism of carotenoid synthesis during Paphiopedilum armeniacum flowering.

Background: Paphiopedilum armeniacum (P. armeniacum), an ornamental plant native to China, is known for its distinctive yellow blossoms. However, the mechanisms underlying P. armeniacum flower coloration remain unclear. Methods: We selected P. armeniacum samples from different flowering stages and conducted rigorous physicochemical analyses. The specimens were differentiated based on their chemical properties, specifically their solubilities in polar solvents. This key step enabled us to identify the main metabolite of flower color development of P. armeniacum, and to complete the identification by High-performance liquid chromatography (HPLC) based on the results. Additionally, we employed a combined approach, integrating both third-generation full-length transcriptome sequencing and second-generation high-throughput transcriptome sequencing, to comprehensively explore the molecular components involved. Results: We combined physical and chemical analysis with transcriptome sequencing to reveal that carotenoid is the main pigment of P. armeniacum flower color. Extraction colorimetric method and HPLC were used to explore the characteristics of carotenoid accumulation during flowering. We identified 28 differentially expressed carotenoid biosynthesis genes throughout the flowering process, validated their expression through fluorescence quantification, and discovered 19 potential positive regulators involved in carotenoid synthesis. Among these candidates, three RCP2 genes showed a strong potential for governing the PDS and ZDS gene families. In summary, our study elucidates the fundamental mechanisms governing carotenoid synthesis during P. armeniacum flowering, enhancing our understanding of this process and providing a foundation for future research on the molecular mechanisms driving P. armeniacum flowering.

IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases.

The success of chimeric antigen receptor (CAR) T cell therapy in treating several hematopoietic malignancies has been difficult to replicate in solid tumors, in part because of T cell exhaustion and eventually dysfunction. To counter T cell dysfunction in the tumor microenvironment, we metabolically armored CAR T cells by engineering them to secrete interleukin-10 (IL-10). We show that IL-10 CAR T cells preserve intact mitochondrial structure and function in the tumor microenvironment and increase oxidative phosphorylation in a mitochondrial pyruvate carrier-dependent manner. IL-10 secretion promoted proliferation and effector function of CAR T cells, leading to complete regression of established solid tumors and metastatic cancers across several cancer types in syngeneic and xenograft mouse models, including colon cancer, breast cancer, melanoma and pancreatic cancer. IL-10 CAR T cells also induced stem cell-like memory responses in lymphoid organs that imparted durable protection against tumor rechallenge. Our results establish a generalizable approach to counter CAR T cell dysfunction through metabolic armoring, leading to solid tumor eradication and long-lasting immune protection.

Superassembled MXene-carboxymethyl chitosan nanochannels for the highly sensitive recognition and detection of copper ions.

Copper ions (Cu2+), as a crucial trace element, play a vital role in living organisms. Thus, the detection of Cu2+ is of great significance for disease prevention and diagnosis. Nanochannel devices with an excellent nanoconfinement effect show great potential in recognizing and detecting Cu2+ ions. However, these devices often require complicated modification and treatment, which not only damages the membrane structure, but also induces nonspecific, low-sensitivity and non-repeatable detection. Herein, a 2D MXene-carboxymethyl chitosan (MXene/CMC) freestanding membrane with ordered lamellar channels was developed by a super-assembly strategy. The introduction of CMC provides abundant space charges, improving the nanoconfinement effect of the nanochannel. Importantly, the CMC can chelate with Cu2+ ions, endowing the MXene/CMC with the ability to detect Cu2+. The formation of CMC-Cu2+ complexes decreases the space charges, leading to a discernible variation in the current signal. Therefore, MXene/CMC can achieve highly sensitive and stable Cu2+ detection based on the characteristics of nanochannel composition. The linear response range for Cu2+ detection is 10-9 to 10-5 M with a low detection limit of 0.095 nM. Notably, MXene/CMC was successfully applied for Cu2+ detection in real water and fetal bovine serum samples. This work provides a simple, highly sensitive and stable detection platform based on the properties of the nanochannel composition.

2D Ordered Mesoporous Lamellar Hetero-Nanochannels with Asymmetric Wettability for Controllable Ion Transport.

Heterogeneous membranes play a crucial role in osmotic energy conversion by effectively reducing concentration polarization. However, most heterogeneous membranes mitigate concentration polarization through an asymmetric charge distribution, resulting in compromised ion selectivity. Herein, hetero-nanochannels with asymmetric wettability composed of 2D mesoporous carbon and graphene oxide are constructed. The asymmetric wettability of the membrane endows it with the ability to suppress the concentration polarization without degrading the ion selectivity, as well as achieving a diode-like ion transport feature. As a result, enhanced osmotic energy harvesting is achieved with a power density of 6.41 W m-2 . This represents a substantial enhancement of 102.80-137.85% when compared to homogeneous 2D membranes, surpassing the performance of the majority of reported 2D membranes. Importantly, the membrane can be further used for high-performance ionic power harvesting by regulating ion transport, exceeding previously reported data by 89.1%.

Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques.

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M-/-CIITA-/-CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16 weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4 weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40 weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected.

The chain mediating roles of anxiety and depression in the relationship between the effects of the COVID-19 pandemic and procrastination in adolescents: a longitudinal study.

BACKGROUND: The relationship between the Coronavirus Disease 2019 (COVID-19) pandemic, which is a traumatic event for adolescents, and procrastination is not clear. Mental health may play an important role in this relationship; however, the underlying mechanisms remain unknown. This study aimed to construct chain mediation models to examine whether anxiety and depression symptoms mediate the effects of the COVID-19 pandemic on procrastination in adolescents. METHODS: A convenience sample of 12 middle and high schools in Harbin, China, with four follow-up online surveys was conducted during the COVID-19 pandemic. A total of 4,156 Chinese adolescents were enrolled in this study, of whom ages 11-18 (Mean = 13.55; SD = 1.18), 50.75% were male, and 93.24% were middle school students. Descriptive demographic analysis and Pearson's correlation analysis of the effects of the COVID-19 pandemic (T1), anxiety(T2), depression (T3), and procrastination (T4) were performed in SPSS 22.0. Chain mediation analysis performed with Mplus 8.3. RESULTS: The effects of the COVID-19 pandemic, anxiety symptoms, depression symptoms, and procrastination were positively correlated (P < 0.01). The effects of the COVID-19 pandemic have a direct link on adolescent procrastination (effect = 0.156; SE = 0.031; 95%CI: 0.092, 0.214), and have three indirect paths on procrastination: the independent mediating role of anxiety symptoms was 29.01% (effect = 0.047; SE = 0.012; 95%CI: 0.024, 0.072), the independent mediating role of depression symptoms was 29.01% (effect = 0.047; SE = 0.010; 95%CI: 0.030, 0.068), as well as the completely chain mediating role of anxiety and depression symptoms was 15.43% (effect = 0.025; SE = 0.005; 95%CI: 0.017, 0.036). CONCLUSIONS: Our results suggest that anxiety and depressive symptoms are part of a causal chain between the effects of the COVID-19 pandemic and procrastination among Chinese adolescents. To effectively reduce their procrastination, attention should be paid to the emotional distress caused to adolescents by major events such as the COVID-19 epidemic. All data were taken from self-reported measures and one city in China, which may bias the results and limit their generalizability.

Dual-functional single-atomic Mo/Fe clusters-decorated C3N5 via three electron-pathway in oxygen reduction reaction for tandemly removing contaminants from water.

Inspired by the development of single-atom catalysts (SACs), the fabrication of multimetallic SACs can be a promising technical approach for the in situ electro-Fenton (EF) process. Herein, dual-functional atomically dispersed Mo-Fe sites embedded in carbon nitride (C3N5) (i.e., MoFe/C3N5) were synthesized via a facile SiO2 template method. The atomically isolated bimetallic configuration in MoFe/C3N5 was identified by combining the microscopic and spectroscopic techniques. The MoFe/C3N5 catalyst on the cathode exhibited a remarkable catalytic activity toward the three electron-dominated oxygen reduction reaction in sodium sulfate, leading to a highly effective EF reaction with a low overpotential for the removal of organic contaminants from wastewater. The new catalyst showed a superior performance over its conventional counterparts, owing to the dual functions of the dual-metal active sites. Density functional theory (DFT) analysis revealed that the dual-functional 50-MoFe/C3N5 catalyst enabled a synergistic action of the Mo-Fe dual single atomic centers, which can alter the adsorption/dissociation behavior and decrease the overall reaction barriers for effective organic oxidation during the EF process. This study not only sheds light on the controlled synthesis of atomically isolated catalyst materials but also provides deeper understanding of the structure-performance relationship of the nanocatalysts with dual active sites for the catalytic EF process. Additionally, the findings will promote the advanced catalysis for the treatment of emerging organic contaminants in water and wastewater.