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Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

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Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled. High-resolution 3D T1-weighted and resting-state functional MRI (rs-fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs-fMRI FC using seed-based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs-fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = -0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD-nFOG group. PD-FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD-nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD-FOG and distinguishing between PD subtypes.

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The synthesis of pseudo-healthy images, involving the generation of healthy counterparts for pathological images, is crucial for data augmentation, clinical disease diagnosis, and understanding pathology-induced changes. Recently, Generative Adversarial Networks (GANs) have shown substantial promise in this domain. However, the heterogeneity of intracranial infection symptoms caused by various infections complicates the model's ability to accurately differentiate between pathological and healthy regions, leading to the loss of critical information in healthy areas and impairing the precise preservation of the subject's identity. Moreover, for images with extensive lesion areas, the pseudo-healthy images generated by these methods often lack distinct organ and tissue structures. To address these challenges, we propose a three-stage method (localization, inpainting, synthesis) that achieves nearly perfect preservation of the subject's identity through precise pseudo-healthy synthesis of the lesion region and its surroundings. The process begins with a Segmentor, which identifies the lesion areas and differentiates them from healthy regions. Subsequently, a Vague-Filler fills the lesion areas to construct a healthy outline, thereby preventing structural loss in cases of extensive lesions. Finally, leveraging this healthy outline, a Generative Adversarial Network integrated with a contextual residual attention module generates a more realistic and clearer image. Our method was validated through extensive experiments across different modalities within the BraTS2021 dataset, achieving a healthiness score of 0.957. The visual quality of the generated images markedly exceeded those produced by competing methods, with enhanced capabilities in repairing large lesion areas. Further testing on the COVID-19-20 dataset showed that our model could effectively partially reconstruct images of other organs.

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Background: Glycoprotein non-metastatic melanoma B (GPNMB)/osteoactivin was first identified in the human melanoma cell lines. GPNMB plays a key role in the anti-inflammatory and antioxidative functions as well as osteoblast differentiation, cancer progression, and tissue regeneration. Recently, GPNMB was used as an anti-aging vaccine for mice. The present study aimed to investigate the potential of biofluid GPNMB as an aging biomarker in humans using serum and urine samples from an aging Chinese population. Methods: We analyzed RNA-sequencing data (GSE132040) from 17 murine organs across different ages to assess the gene expression of potential ageing biomarkers. Spearman's correlation coefficients were used to evaluate the relationship between gene expression and age. Meanwhile, a cross-sectional population study was conducted, which included 473 participants (aged 25-91 years), a representative subset of participants from the Peng Zu Study on Healthy Ageing in China (Peng Zu Cohort). Biofluid GPNMB levels were measured by ELISA. The associations of serum and urine GPNMB levels with various clinical and anthropometrical indices were assessed using ANOVA, Kruskal-Wallis H test, and univariate and multivariate linear regression analyses. Results: In mice, the Gpnmb mRNA expression levels showed a significant positive association with age in multiple organs in mice (P < 0.05). In Peng Zu Cohort, biofluid (both serum and urine) GPNMB levels showed a positive correlation with age (P < 0.05). Univariate linear regression analysis revealed that serum GPNMB levels were negatively associated with skeletal muscle mass index (SMI, P < 0.05) and insulin-like growth factor 1 (IGF-1, P < 0.05), and urine GPNMB levels showed a negative association with total bile acids (TBA, P < 0.05). Multivariate linear regression analysis further indicated that serum GPNMB levels negatively correlated with the systemic immune-inflammation index (SII, P < 0.05), and the urine GPNMB levels maintained a negative association with TBA (P < 0.05), additionally, urine GPNMB levels in men were significantly lower than in women (P < 0.05). Conclusions: The biofluid GPNMB was a strong clinical biomarker candidate for estimating biological aging.

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BACKGROUND: Diethanolamine, monoethanolamine, iminodiacetic acid, and glycine are important fine chemical intermediates, often requiring simultaneous quantitative analysis in various applications. This presents the challenge of accurately quantifying multiple substances within a single sample. The catalytic dehydrogenation of diethanolamine and monoethanolamine has garnered significant research interest, yet no analytical method has been reported for the simultaneous quantification of reactants and products in the dehydrogenation reaction mixtures of different alkanolamines. RESULTS: A high-performance liquid chromatography (HPLC) method has been developed for the simultaneous quantification of diethanolamine (DEA), iminodiacetic acid (IDA), glycine (Gly), and monoethanolamine (MEA) in aqueous solutions using 2,4-dinitrofluorobenzene (DNFB) for pre-column derivatization. The method demonstrated excellent linearity, with correlation coefficients (R2) of 0.9999, 0.9997, and 0.9998 for IDA, DEA, and Gly, respectively. The detection limits (LODs) were 0.02, 0.08, and 0.01 mg L-1, respectively. The quantification limits (LOQs) were 0.06, 0.24, and 0.03 mg L-1, respectively. Spiked recovery rates ranged from 96.99 % to 104.32 %, with relative standard deviations (RSDs) between 0.70 % and 3.03 %. For MEA and Gly, the R2 values were 0.9970 and 0.9990, the LODs were 0.12 and 0.01 mg L-1, the LOQs were 0.36 and 0.03 mg L-1, and spiked recoveries ranged from 96.24 % to 104.82 %, with RSDs between 1.22 % and 3.68 %. Compared to other methods, this HPLC approach offers superior sensitivity, accuracy, and precision. SIGNIFICANCE: This method provides a robust reference for the individual or simultaneous quantification of alkanolamines, glycine, and iminodiacetic acid in aqueous matrices. It offers new insights into the simultaneous analysis of alkanolamines with multiple organic acids in complex matrices. Additionally, the method can guide the optimization of catalytic dehydrogenation processes for alkanolamines, potentially extending the advantages of dehydrogenation catalysts to other reactions.

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An active chitosan (CS) film containing a nano-hydroxyapatite-tea polyphenol (HAP-TP) complex was designed and prepared. The effects of HAP-TP loading on the structural and physicochemical properties of the CS-based film were evaluated. The mechanical and thermal properties of the film were significantly improved by the resulting intermolecular interactions and formation of hydrogen bonds between HAP-TP and CS, which reduced the water vapor and oxygen permeabilities of the film by 29.78 and 35.59 %, respectively. The CS-HAP-TP film exhibited excellent slow-release behavior and antioxidant activity, with a cumulative release rate at 700 h 6.79 % lower than that of CS-TP films. The CS-HAP-TP film significantly inhibited the deterioration of semi-dried golden pompano, and thus helped to retain the taste of umami and sweet amino acids in fish samples, while reducing off-flavor generation. The film therefore shows considerable potential as an active packaging material for the preservation of semi-dried fish products.

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A straightforward copper-catalyzed deborodeuteration of arylboronic acids and borates was achieved, employing the cost-effective deuterium source D2O. This protocol demonstrates wide substrate applicability, exceptional deuterium incorporation efficiency, and favorable tolerance for various functional groups. Therefore, this approach offers a mild option for further applications in valuable deuterium molecule synthesis.

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Plants have complex detoxification and metabolic systems that enable them to deal with environmental pollutants. We report accumulation of the pesticide isoproturon (IPU) in a BR signaling pathway for mutant bzr4-3/5 rice to be significantly higher than in wild-type (WT) rice controls and for exogenous 24-epibrassinolide to reverse toxic symptoms in WT rice but not in mutants. A genome-wide RNA sequencing study of WT/bzr4 rice is performed to identify transcriptomic changes and metabolic mechanisms under IPU exposure. Three differentially expressed genes in yeast cells increase the degradation rate of IPU in a growth medium by factors of 1.61, 1.51, and 1.29 after 72 h. Using UPLC/Q-TOF-MS/MS, five phase I metabolites and five phase II conjugates are characterized in rice grains, with concentrations generally decreasing in bzr4 rice grains. OsBZR4, a regulator of IPU degradation in rice, may eliminate IPU from edible parts of food crops by regulating downstream metabolic genes.

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While Mammarenavirus Wenzhouense (WENV) is broadly distributed across Asia, the dynamics of WENV infection remain unclear. In this study, a field-derived strain of WENV was used to inoculate Sprague Dawley (SD) rats by intramuscular injection, and the process of viral infection was observed over the course of 28 d. Viral RNA became detectable in the blood at 3 dpi and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 dpi, and then began to decline by 14 d, but remained detectable in intestine and brain tissues at 21 and 28 dpi. Viral shedding was detected from fecal samples for 5 d, from 6 to 11 dpi using qRT-PCR, and was recovered from feces collected at 8 dpi. Horizontal contact infection occurred among cage-mates at 14 and 21 dpi. Antibodies against the nucleocapsid were detected at 5 dpi, and then increased and persisted until the end of the experiment. These results enabled us to determine the kinetics of viremic response, viral shedding in feces, and horizontal transmission dynamics, as well as the potential sites for WENV replication and viral maintenance in nature.

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The effects of phenolic acid grafted-chitosan hydrocolloids (CS-g-GA/FA) on aldehyde contents from lipid oxidation in golden pompano fillets during pan-frying was investigated with an established high-performance liquid chromatography-mass spectrum method. Results indicated that pan-frying induced profound lipid oxidation and aldehydes generation with propanal, hexanal, nonanal, trans, trans-2,4-decadienal, and 4-hydroxy-2-nonenal as the abundant species. CS-g-FA and CS-g-GA effectively decreased their contents by 23.74-27.42 %, 61.69-67.42 %, 41.83-53.91 %, 29.91-48.79 %, and 61.57-65.39 % after 3 min. Most aldehyde contents decreased with the extension of pan-frying time due to the volatilization and reaction. In terms of substrate depletion, CS-g-phenolic acids effectively inhibited unsaturated fatty acids oxidation due to their decent antioxidant activity than CS. The significant lower retention rates of aldehydes in the CS-g-phenolic acids groups compared with control in chemical mode confirmed the carbonyl ammonia condensation. These results suggested that CS-g-phenolic acids serve as novel coating to reduce hazardous compounds during aquatic products thermal processing.

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Objective: To investigate the long-term effectiveness of Ni-Ti memory alloy tripod fixator in the treatment of Kienböck disease. Methods: The clinical data of 22 patients with Kienböck disease who were treated with Ni-Ti memory alloy tripod fixator between January 2011 and September 2013 and followed up more than 10 years was retrospectively analyzed. There were 14 males and 8 females with an average age of 45 years (range, 20-64 years). The Lichtman staging was stage Ⅲb. According to AO/Association for the Study of Internal Fixation (AO/ASIF) classification, there were 6 cases of type B1, 2 cases of type B2, 10 cases of type B3, and 4 cases of type C2. The disease duration ranged from 18 to 50 months, with an average of 30.7 months. The operation time, intraoperative blood loss, and complications were recorded. Wrist height ratio and scapholunate angle were measured by wrist anteroposterior and lateral X-ray films before and after operation. The grip strength of bilateral hands was measured by Jamar dynamometer. The wrist pain was evaluated by visual analogue scale (VAS) score, and the wrist function was evaluated by Mayo score, and the radial deviation, ulnar deviation, dorsiflexion, and palmar flexion range of motion of wrist were measured. Results: The operation time was 45-60 minutes, with an average of 52.21 minutes; the intraoperative blood loss was 50-60 mL, with an average of 58.63 mL. No nerve or blood vessel injury occurred during operation. All patients were followed up 10-13 years (mean, 11.3 years). X-ray films at 3 months after operation showed that the density of lunate bone was lower than that before operation. Satisfactory fusion of the scapho-trapezio-trapezoeid joint was achieved at 3-6 months after operation (mean, 4.5 months), and the wrist height ratio and the scapholunate angle after fusion significantly improved when compared with those before operation ( P<0.05). Wrist pain relieved, scaphoid rotation and dislocation improved, and no radiocarpal joint degeneration was found during follow-up, and no internal fixator loosening, breakage, or lunate bone necrosis occurred. At last follow-up, the wrist radial deviation, ulnar deviation, dorsiflexion, and palmar flexion range of motion, VAS score, and grip strength of the affected side significantly improved when compared with those before operation ( P<0.05); the grip strength of the affected side recovered to 99.00%±1.25% of the healthy side. Mayo score ranged from 72 to 93, with an average of 85; 14 cases were rated as excellent, 5 good, and 3 satisfactory, the excellent and good rate was 86.4%. Conclusion: In the treatment of stage Ⅲb Kienböck's disease, the scapho-trapezio-trapezoeid joint usion using Ni-Ti memory alloy tripod fixator can effectively reduce pain, improve hand function, and prevent further deterioration, and achieve good long-term effectiveness.

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Neurodegenerative diseases (NDDs) are increasingly prevalent with global aging, demanding effective treatments. Exosomes, which contain biological macromolecules such as RNA (including miRNAs) and proteins like α-synuclein, tau, and amyloid-beta, are gaining attention as innovative therapeutics. This comprehensive review systematically explores the potential roles of exosomes in NDDs, with a particular focus on their role in synaptic dysfunction. We present the synaptic pathophysiology of NDDs and discuss the mechanisms of exosome formation, secretion, and action. Subsequently, we review the roles of exosomes in different types of NDDs, such as Alzheimer's disease and Parkinson's disease, with a special focus on their regulation of synaptic function. In addition, we explore the potential use of exosomes as biomarkers, as well as the challenges and opportunities in their clinical application. We provide perspectives on future research directions and development trends to provide a more comprehensive understanding of and guidance for the application of exosomes in the treatment of NDDs. In conclusion, exosomes rich in biological macromolecules, as a novel therapeutic strategy, have opened up new possibilities for the treatment of NDDs and brought new hope to patients.

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Toxoplasma gondii, a pathogenic apicomplexan parasite, infects approximately one third of the world's population and poses a serious threat to global public health. Microneme proteins (MICs) secreted by the microneme, an apical secretory organelle of T. gondii, play important roles in the invasion, motility, and intracellular survival of T. gondii. In this study, we selected 11 genes of interest (GOIs) of T. gondii, tentative MICs predicted to be localized in micronemes, and we used the CRISPR-Cas9 system to construct epitope tagging strains and gene knockout strains to explore the localization and function of these 11 tentative MICs. Immunofluorescence assay showed that nine tentative MICs (TGME49_243930, TGME49_200270, TGME49_273320, TGME49_287040, TGME49_261710, TGME49_205680, TGME49_304490, TGME49_245485, and TGME49_224620) were localized or partially localized in the microneme, consistent with the prediction. However, TGME49_272380 and TGME49_243790 showed different localizations from the prediction, being localized in the endoplasmic reticulum and the dense granule, respectively. Further functional characterization of the 11 RHΔGOI strains revealed that deletion of these 11 GOIs had no significant effect on plaque formation, intracellular replication, egress, invasion ability, and virulence of T. gondii. Although these 11 GOIs are not essential genes for the growth and virulence of tachyzoites of type I RH strain, they may have potential roles in other developmental stages or other genotypes of T. gondii. Thus, further research should be performed to explore the possible role of the nine mics and the other two GOIs in other life cycle stages and other genotypes of T. gondii.

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The real-time structural changes of the molecular space conformation of myofibrillar protein microgels (MPM) after heat treatment (90 °C, 30 min) were analyzed by molecular dynamics simulation, and the structural properties and changes of MPM at the oil-water interface were analyzed by the combination of Raman spectroscopy and molecular dynamics simulation. The shift in the oil ratio had a major impact on the transformation of disulfide bonds within the protein molecule. Simultaneously, it caused tryptophan and tyrosine residues (I850 cm-1/ I850 cm-1 > 1) to become exposed, increasing the locations of amino acid residues in the protein that interact with the oil phase. HIPE with different oil phases influenced the change in spatial structural conformation of MPM, and there was a flexible structural change in the molecular space. The HIPE system, which was stabilized by 3.0 wt% MPM and 0.75 oil phase, exhibited a thixotropic recovery of >70 % and the highest elastic modulus G' (822.14 Pa) based on the rheological behavior. It is expected to provide a theoretical basis for the development and utilization of high internal phase emulsion stabilized by microgel protein in food industry.

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Background: Lumbar disc degeneration (LDD) is a prevalent condition characterized by the decreased viability and functional impairment of nucleus pulposus mesenchymal stem cells (NPMSCs). Shaoyao-Gancao decoction (SGD), a traditional Chinese medicine formula, has been used to treat LDD, but its active components and mechanisms are unclear. Methods: An integrative network pharmacology and transcriptome analysis were conducted to identify bioactive compounds in SGD that could target LDD. NPMSCs were cultured under mechanical compression as a cellular model of LDD. A rat model of annulus fibrosus needle-puncture was established to induce intervertebral disc degeneration. The effects of quercetin, a predicted active component, on alleviating compression-induced NPMSC death and LDD were evaluated in vitro and in vivo. Results: The analysis identified hypoxia-inducible factor 1-alpha (HIF1A) as a potential target of quercetin in LDD. HIF1A was upregulated in degenerated human disc samples and compression-treated NPMSCs. Quercetin treatment alleviated compression-induced oxidative stress, apoptosis, and loss of viability in NPMSCs by stabilizing HIF1A. The protective effects of quercetin were abrogated by HIF1A inhibition. In the rat model, quercetin ameliorated intervertebral disc degeneration. Conclusion: Our study identified HIF1A as a protective factor against compression-induced cell death in NPMSCs. Quercetin, a bioactive compound found in the traditional Chinese medicine formula SGD, improved the survival of NPMSCs and alleviated LDD progression by stabilizing HIF1A. Targeting the HIF1A pathway through natural compounds like quercetin could represent a promising strategy for the clinical management of LDD and potentially other degenerative disc diseases.

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Tumor cell-derived prostaglandin E2 (PGE2) is a tumor cell-intrinsic factor that supports immunosuppression in the tumor microenvironment (TME) by acting on the immune cells, but the impact of PGE2 signaling in tumor cells on immunosuppressive TME is unclear. We demonstrate that deleting the PGE2 synthesis enzyme or disrupting autocrine PGE2 signaling through EP4 receptors on tumor cells reverses the T cell-low, myeloid cell-rich TME, activates T cells, and suppresses tumor growth. Knockout (KO) of Ptges (the gene encoding PGE2 synthesis enzyme mPGES-1) or the EP4 receptor gene (Ptger4) in KPCY (KrasG12D/P53R172H/Yfp/CrePdx) pancreatic tumor cells abolished growth of implanted tumors in a T cell-dependent manner. Blockade of the EP4 receptor in combination with immunotherapy, but not immunotherapy alone, induced complete tumor regressions and immunological memory. Mechanistically, Ptges and Ptger4 KO tumor cells exhibited altered T and myeloid cell attractant chemokines, became more susceptible to TNF-α killing, and exhibited reduced adenosine synthesis. In hosts treated with an adenosine deaminase inhibitor, Ptger4 KO tumor cells accumulated adenosine and gave rise to tumors. These studies reveal an unexpected finding - a non-redundant role for the autocrine mPGES1-PGE2-EP4 signaling axis in pancreatic cancer cells - further nominating mPGES-1 inhibition and EP4 blockade as immune-sensitizing therapy in cancer.

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With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults.

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Total knee arthroplasty (TKA) is a well-established treatment for end-stage knee osteoarthritis. However, in patients with concomitant extra-articular deformities, conventional TKA techniques may lead to unsatisfactory outcomes and higher complication rates. This review summarizes the application of navigated TKA for treating knee osteoarthritis with extra-articular deformities. The principles and potential benefits of computer navigation systems, including improved component alignment, soft tissue balancing, and restoration of mechanical axis, are discussed. Research studies demonstrate that navigated TKA can effectively correct deformities, relieve pain, and improve postoperative joint function and quality of life compared with conventional methods. The advantages of navigated TKA in terms of surgical precision, lower complication rates, and superior functional recovery are highlighted. Despite challenges like the learning curve and costs, navigated TKA is an increasingly indispensable tool for achieving satisfactory outcomes in TKA for knee osteoarthritis patients with extra-articular deformities.

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Endosymbionts provide essential nutrients for hosts, promoting growth, development, and reproduction. However, the molecular regulation of nutrient transport from endosymbiont to host is not well understood. Here, we used bioinformatic analysis, RNA-Sequencing, luciferase assays, RNA immunoprecipitation, and in situ hybridization to show that a bacteriocyte-distributed MRP4 gene (multidrug resistance-associated protein 4) is negatively regulated by a host (aphid)-specific microRNA (miR-3024). Targeted metabolomics, microbiome analysis, vitamin B6 (VB6) supplements, 3D modeling/molecular docking, in vitro binding assays (voltage clamp recording and microscale thermophoresis), and functional complementation of Escherichia coli were jointly used to show that the miR-3024/MRP4 axis controls endosymbiont (Serratia)-produced VB6 transport to the host. The supplementation of miR-3024 increased the mortality of aphids, but partial rescue was achieved by providing an external source of VB6. The use of miR-3024 as part of a sustainable aphid pest-control strategy was evaluated by safety assessments in nontarget organisms (pollinators, predators, and entomopathogenic fungi) using virus-induced gene silencing assays and the expression of miR-3024 in transgenic tobacco. The supplementation of miR-3024 suppresses MRP4 expression, restricting the number of membrane channels, inhibiting VB6 transport, and ultimately killing the host. Under aphids facing stress conditions, the endosymbiont titer is decreased, and the VB6 production is also down-regulated, while the aphid's autonomous inhibition of miR-3024 enhances the expression of MRP4 and then increases the VB6 transport which finally ensures the VB6 homeostasis. The results confirm that miR-3024 regulates nutrient transport in the endosymbiont-host system and is a suitable target for sustainable pest control.

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In the electrochemical nitrogen reduction reaction (NRR), a leverage relationship exists between NH3-producing activity and selectivity because of the competing hydrogen evolution reaction (HER), which means that high activity with strong protons adsorption causes low product selectivity. Herein, we design a novel metal-organic hydrogen bonding framework (MOHBF) material to modulate this leverage relationship by a hydrogen-bond-regulated proton transfer pathway. The MOHBF material was composited with reduced graphene oxide (rGO) to form a Ni-N2O2 molecular catalyst (Ni-N2O2/rGO). The unique structure of O atoms in Ni-O-C and N-O-H could form hydrogen bonds with H2O molecules to interfere with protons being directly adsorbed onto Ni active sites, thus regulating the proton transfer mechanism and slowing the HER kinetics, thereby modulating the leverage relationship. Moreover, this catalyst has abundant Ni-single-atom sites enriched with Ni-N/O coordination, conducive to the adsorption and activation of N2. The Ni-N2O2/rGO exhibits simultaneously enhanced activity and selectivity of NH3 production with a maximum NH3 yield rate of 209.7 µg h-1 mgcat.-1 and a Faradaic efficiency of 45.7%, outperforming other reported single-atom NRR catalysts.