Adalimumab-induced manic episode in an adolescent with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children, and adalimumab is one of the primary treatment options. Although it is widely used for inflammatory diseases, there is limited research on its safety and efficacy in patients with psychiatric disorders or in those with inflammatory diseases who also have comorbid psychiatric conditions. CASE REPORT: We report a 12-year-old adolescent boy who presented with emotional instability for 1 year, exacerbated leading to hospital admission in the past month. Upon detailed evaluation after admission, it was found that the patient's emotional fluctuations may be related to the use of Adalimumab. Follow-up after psychiatric inpatient treatment revealed that the patient did not experience emotional excitement again after discontinuing Adalimumab. CONCLUSIONS: Although tumor necrosis factor-α inhibitors have positive effects on the emotional, cognitive, and physical functions of patients with inflammatory diseases, their use may induce mood swings in patients with comorbid mood disorders. This is particularly important for adolescents with rapid mood changes, where greater caution is required. Further research is necessary to clarify the correlation between the adverse effects of these drugs and their impact on patients with bipolar disorder.

Redox-Responsive Nanopesticides Based on Natural Polymers for Environmentally Safe Delivery of Pesticides with Enhanced Foliar Dispersion and Washout Resistance.

Based on the modified cross-linking of the degradable natural polymers chitosan oligosaccharides (COS) and gelatin (GEL) via introduction of a functional bridge 3,3'-dithiodipropionic acid, this study constructed an environmentally responsive dinotefuran (DNF) delivery system (DNF@COS-SS-GEL). The introduction of the disulfide bond (-S-S-) endowed DNF@COS-SS-GEL with redox-responsive properties, allowing for the rapid release of pesticides when stimulated by glutathione (GSH) in the simulated insect. Compared with commercial DNF suspension concentrate (DNF-SC), DNF@COS-SS-GEL showed superior wet spreading and retention performance on cabbage leaves with a reduced contact angle (57°) at 180 s and 4-fold increased retention capacity after rainfall washout. Nanoencapsulation effectively improved the UV-photostability with only a 31.4% decomposition rate of DNF@COS-SS-GEL at 96 h. The small scale and large specific surface area resulted in excellent uptake and transportation properties in plants as well as higher bioactivity against Plutella xylostella larvae. This study will help promote sustainable agricultural development by reducing environmental pollution through improved pesticide utilization.

Tuning the fluidity and protein corona of ultrasound-responsive liposomal nanovaccines to program T cell immunity in mice.

Inducing high levels of antigen-specific CD8α+ T cells in the tumor is beneficial for cancer immunotherapy, but achieving this in a safe and effective manner remains challenging. Here, we have developed a designer liposomal nanovaccine containing a sonosensitizer (LNVS) to efficiently program T cell immunity in mice. Following intravenous injection, LNVS accumulates in the spleen in a protein corona and fluidity-dependent manner, leading to greater frequencies of antigen-specific CD8α+ T cells than soluble vaccines (the mixture of antigens and adjuvants). Meanwhile, some LNVS passively accumulates in the tumor, where it responds to ultrasound (US) to increase the levels of chemokines and adhesion molecules that are beneficial for recruiting CD8α+ T cells to the tumor. LNVS + US induces higher levels of intratumoral antitumor T cells than traditional sonodynamic therapy, regresses established mouse MC38 tumors and orthotopic cervical cancer, and protects cured mice from relapse. Our platform sheds light on the importance of tuning the fluidity and protein corona of naovaccines to program T cell immunity in mice and may inspire new strategies for cancer immunotherapy.

In vivo electrical properties of the healthy liver and the hepatic tumor in a mouse model between 1 Hz and 1 MHz during a thermal treatment.

Objective: Understansding the changing patterns of in vivo electrical properties for the target tissue is crucial for the accurate temperature monitoring and the treatment efficacy in thermal therapy. Our research aims to investigate the changing patterns and the reversibility of in vivo electrical properties for both healthy livers and liver tumors in a mouse model over a frequency range of 1 Hz to 1 MHz at temperatures between 30 °C to 90 °C.Methods and materials: The mice were anesthetized and the target organ was exposed. An 808-nm near-infrared laser was employed as the heating source to heat the organ in vivo. The four-needle electrode, connected to an impedance analyzer, was utilized to obtain the impedance at varying temperatures, which were monitored by a thermocouple.Results: The findings indicated a gradual decline in impedance with an increase in temperature. Furthermore, the impedance was normalized to that at 30 °C, and the real part of the normalized impedance was defined as the k-values, which range from 0 to 1. The results demonstrated a linear correlation between k-values and temperatures (R2 > 0.9 for livers and R2 > 0.8 for tumors). Significant differences were observed between livers and tumors at 1, 10 and 50 kHz (p < 0.05). Additionally, it was demonstrated that the electrical properties could be reversed when the temperature was below or equal to 45 °C.Conclusion: We believe that these results will contribute to the advancement of radiofrequency ablation systems and the development of techniques for temperature monitoring during liver thermal treatment.

Ningxiang Pig-Derived Parabacteroides distasonis HNAU0205 Alleviates ETEC-Induced Intestinal Apoptosis, Oxidative Damage, and Inflammation in Piglets.

Weaning is a critical stage in the growth and development of piglets, often inducing stress reactions. This study aims to investigate the effects of Parabacteroides distasonis (PBd) derived from Ningxiang pigs on growth performance, intestinal apoptosis, oxidative damage, and inflammation in ETEC-challenged weaned piglets. A total of 22 Duroc × Landrace × Yorkshire (DLY) piglets, 24 days old with similar body weights, were randomly divided into three groups: Control (n = 7), ETEC (n = 7), and PBd + ETEC (n = 8). The results show that, compared to the Control group, ETEC challenge led to decreased growth performance, reduced villus height in the duodenum and jejunum, increased crypt depth in the duodenum, a decreased villus-height-to-crypt-depth ratio, increased expression of apoptosis-related genes (Caspase-8 and Caspase-9), increased expression of oxidative damage-related genes (Nrf2, GSH-PX, mTOR, and Beclin1), increased expression of inflammation-related genes (Myd88, P65, TNF-α, and IL-6), and reduced the contents of SCFAs in the colonic chyme (acetate, propionate, butyrate, valerate, and total SCFAs). Compared to the ETEC group, the PBd + ETEC group alleviated the reduction in growth performance, mitigated intestinal morphological damage, and reduced the expression of the aforementioned apoptosis, oxidative damage, and inflammation-related genes with the increase in SCFAs. In conclusion, PBd derived from Ningxiang pigs effectively reduces ETEC-induced intestinal damage in weaned piglets, improves intestinal health, and increases the content of SCFAs in the colonic chyme, thereby enhancing growth performance.

CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway.

Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.

A biomimetic lubricating nanosystem for synergistic therapy of osteoarthritis.

Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core-shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications.

A photothermal effect-based chiral sensor for chiral discrimination and sensitive detection.

Chiral analysis with simple devices is of great importance for analytical chemistry. Based on the photothermal (PT) effect, a simple chiral sensor with a portable laser device as the light source and a thermometer as the detection tool was developed for the chiral recognition of tryptophan (Trp) isomers and the sensitive sensing of one isomer (L-Trp). Gold nanorods (GNRs), which have outstanding photo-thermal conversion ability due to their localized surface plasma resonance (LSPR) effect, are used as PT reagents, and biomacromolecules bovine serum albumin (BSA) are used as natural chiral sources, and thus, GNRs@BSA was obtained through Au-S bonds. The resultant GNRs@BSA displays higher affinity toward L-Trp than D-Trp owing to the inherent chirality of BSA. Under the irradiation of near-infrared (NIR) light, the temperature of GNRs@BSA//L-Trp is greatly lower than that of GNRs@BSA//D-Trp due to its greatly decreased thermal conductivity, and thus chiral discrimination of Trp isomers can be achieved. In addition, the developed PT effect-based chiral sensor can be used for sensitive detection of L-Trp, and the linear range and limit of detection (LOD) are 1 µM-10 mM and 0.43 µM, respectively.

A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors.

Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired by the structure of a virus that utilizes internal viral proteins to tune the loading and cytosolic delivery of viral nucleic acids, we developed a liponanogel (LNG)-based platform to overcome the delivery challenges of poly(I:C). The LNG comprised an anionic polymer hyaluronic acid-based nanogel core coated by a lipid shell, which served as a protective layer to stabilize the nanogel core in the lungs. The nanogel core was protonated within acidic endosomes to enhance the endosomal membrane permeability and cytosolic delivery of poly(I:C). After pulmonary delivery, LNG-poly(I:C) induced 13.7-fold more IFNß than poly(I:C) alone and two-fold more than poly(I:C) loaded in the state-of-art lipid nanoparticles [LNP-poly(I:C)]. Additionally, LNG-poly(I:C) induced more potent CD8+ T-cell immunity and stronger therapeutic effects than LNP-poly(I:C). The combination of LNG-poly(I:C) and PD-L1 targeting led to regression of established lung metastases. Due to the ease of manufacturing and the high biocompatibility of LNG, pulmonary delivery of LNG may be broadly applicable to the treatment of different lung tumors and may spur the development of innovative strategies for cancer immunotherapy. Significance: Pulmonary delivery of poly(I:C) with a virus-inspired inhalable liponanogel strongly activates cytosolic MDA5 and RIG-I and stimulates antitumor immunity, representing a promising strategy for safe and effective treatment of metastatic lung tumors.

An electrochemical sensor based on molecularly imprinted poly(o-phenylenediamine) for the detection of thymol.

A molecularly imprinted electrochemical sensor was facilely fabricated for the detection of thymol (THY). o-Phenylenediamine (oPD) was used as the functional monomer and electropolymerized on the surface of the glassy carbon electrode (GCE) by using THY as the templates. After the THY templates were removed with 50 % (v/v) ethanol, imprinted cavities complementary to the templates were formed within the poly(o-phenylenediamine) (PoPD) films. The resultant molecularly imprinted PoPD/GCE (MI-PoPD/GCE) was used for the detection of THY, and a wide linear range from 0.5 to 100 µM with a low limit of detection (LOD) of 0.084 µM were obtained under the optimal conditions. The developed MI-PoPD/GCE also displays high selectivity, reproducibility and stability for THY detection. Finally, the content of THY in the real samples was accurately determined by the as-fabricated MI-PoPD/GCE, demonstrating its high practicability and reliability.

Associations between dietary habits and bipolar disorder: a diet-wide mendelian randomization study.

Background: Diet/nutrition is critically important in the pathogenesis, progression, and treatment outcomes of various mental disorders. Current research predominantly focuses on the role of diet in the development and treatment of depression, with less attention given to the relationship between diet and Bipolar Disorder (BD). Method: We employed Mendelian Randomization (MR) to investigate the relationship between 28 dietary habits and BD. An analysis was conducted using publicly available genome-wide association study data from the UK Biobank dataset. Various dietary habits were analyzed as exposures with BD as the outcome, mainly using the Inverse Variance Weighted (IVW) method. Results: Intake of non-oily fish and sponge pudding both have a positive association with BD. Oily fish, dried fruit, apples, salt, and cooked vegetables intake also appeared potentially risky for BD, although the possibility of false positives cannot be ruled out. Sensitivity analysis further confirmed the robustness of these findings. Conclusion: Our research provides evidence of a relationship between various dietary habits and BD. It underscores the need for careful dietary management and balance to reduce the risk of BD, suggesting caution with dietary preferences for fish and sponge pudding. Furthermore, more detailed studies are needed to further understand the potential impacts of high-sugar and high-protein diets on BD development.

Photothermal COFs with donor-acceptor structure for friction reduction and antiwear.

For the first time, a novel donor-acceptor structured COF with excellent photothermal conversion and mono-dispersity in various oils without any further modification is reported; it realized responsive friction reduction, excellent antiwear and long-time lubrication.

Seasonal patterns in Chinese population: Validating the seasonal pattern assessment questionnaire and exploring associations with psychiatric diagnoses and biological rhythms.

Seasonal patterns (SP) exert a notable influence on the course and prognosis of patients with affective disorders, serving as a specifier in diagnosis. However, there is limited exploration of seasonality among psychotic patients, and the distinctions in seasonality among psychiatric patients remain unclear. In this study, we enrolled 198 psychiatric patients with anxiety and depressive disorders (A&D), bipolar disorder (BD), and schizophrenia (SZ), as well as healthy college students. Online questionnaires, including the Seasonal Pattern Assessment Questionnaire (SPAQ) for seasonality, the Morningness and Eveningness Questionnaire-5 (MEQ-5) for chronotypes, and the Pittsburgh Sleep Quality Index (PSQI), were administered. The validity and reliability of the Chinese version of the SPAQ were thoroughly analyzed, revealing a Cronbach's alpha of 0.896 with a two-factor structure. Results indicated that higher seasonality was correlated with poorer sleep quality and a more delayed chronotype (p < 0.05). Significant monthly variations were particularly evident in BD, specifically in mood, appetite, weight, social activities, and sleep dimensions (p < 0.001). In summary, the Chinese version of SPAQ is validated, demonstrating moderate correlations between seasonality, chronotype, and sleep quality. BD patients exhibited the strongest seasonality, while mood disorder patients displayed more delayed chronotypes than SZ.

π-π+ Interaction Promoting the Absorption of Electroactive Chiral Selectors into the Cavity of Conductive Covalent Organic Framework for Enantioselective Sensing of Electrochemically Silent Molecules.

To date, achieving enantioselective electroanalysis for electrochemically silent chiral molecules is still highly desired. Here, an ionic covalent organic framework (COF) consisting of the pyridinium cation was derived from the tripyridinium Zincke salt and 1,4-phenylenediamine in a one-pot reaction. The electrochemical measurements revealed that the ionic backbone contributed to the electron transfer with a low charge transfer resistance. Besides, the π-π+ interaction between the pyridinium cation and ferrocenyl unit can promote the absorption of electroactive chiral ferrocenyl reagents into the hole of COF, so as to afford the electrochemical signals by themselves, replacing the testing enantiomers. As a result, the electroactive complex used as an electrochemical platform was highly effective at enantiomerically recognizing amino alcohols (prolinol, valinol, leucinol, and alaninol) and amino acids (methionine, serine, and penicillamine), giving the ratios of current intensity between l- and d-enantiomers in the range of 1.46-1.72. Moreover, the density functional theory calculations determined the possible intermolecular interactions between the testing enantiomers and chiral selector: namely, hydrogen bonds and electrostatic attractions. Overall, the present work offers an effective strategy to enlarge the electrochemical scope for chiral recognition based on electroactive chiral COFs.

Ginsenosides from Panax ginseng as potential therapeutic candidates for the treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestine, which significantly affects patients' quality of life. As a perennial plant with the homology of medicine and food, Panax ginseng is known for its substantial anti-inflammatory effects in various inflammatory disorders. Ginsenosides, the main bioactive compounds of P. ginseng, are recognized for their efficacy in ameliorating inflammation. PURPOSE: Over the past decade, approximately 150 studies have investigated the effects of P. ginseng and ginsenosides on IBD treatment and new issues have arisen. However, there has yet to be a comprehensive review assessing the potential roles of ginsenosides in IBD therapy. METHOD: This manuscript strictly adheres to the PRISMA guidelines, thereby guaranteeing systematic synthesis of data. The research articles referenced were sourced from major scientific databases, including Google Scholar, PubMed, and Web of Science. The search strategy employed keywords such as "ginsenoside", "IBD", "colitis", "UC", "inflammation", "gut microbiota", and "intestinal barrier". For image creation, Figdraw 2.0 was methodically employed. RESULTS: Treatment with various ginsenosides markedly alleviated clinical IBD symptoms. These compounds have been observed to restore intestinal epithelia, modulate cellular immunity, regulate gut microbiota, and suppress inflammatory signaling pathways. CONCLUSION: An increasing body of research supports the potential of ginsenosides in treating IBD. Ginsenosides have emerged as promising therapeutic agents for IBD, attributed to their remarkable efficacy, safety, and absence of side effects. Nevertheless, their limited bioavailability presents a substantial challenge. Thus, efforts to enhance the bioavailability of ginsenosides represent a crucial and promising direction for future IBD research.

Visual and electrochemical chiral discrimination of tryptophan isomers with shikimic acid chiral ionic liquids-copper ions complex.

Efficient discrimination of amino acids (AAs) isomers is of significant importance for life science and analytical chemistry. Here, a dual-mode chiral discrimination strategy is proposed for visual and electrochemical chiral discrimination of tryptophan (Trp) isomers. Shikimic acid chiral ionic liquids (SCIL) is coordinated with copper ions (Cu2+), and the obtained SCIL-Cu2+ can form ternary complexes with the Trp isomers. Owing to the inherent chirality of SCIL and the reverse homochirality of L-Trp and D-Trp, the ternary complex of SCIL-Cu-D-Trp has higher stability than SCIL-Cu-L-Trp, as revealed by the calculated stability constants (K) and changes in Gibbs free energy (ΔG). The difference in the stability can be utilized for the chiral discrimination of L-Trp and D-Trp, resulting in discernible differences in colors and the electrochemical signals of the Trp isomers. Besides Trp, the isomers of phenylalanine (Phe) can also be discriminated by the proposed dual-mode chiral discrimination strategy with the SCIL-Cu2+ complex.

Long-circulating nanoparticles as passive targeting nanocarriers for the treatment of thrombosis.

Thrombosis is the major cause of cardiovascular diseases. Only a small subset of patients could benefit from thrombolytic therapy due to the high bleeding risk brought about by the repeated administration of thrombolytic drugs. Nanoparticles with targeting ligands have been developed as nanocarriers of thrombolytic drugs to deliver the drug to the thrombus through active targeting. However, the passive targeting effect of nanoparticles on the thrombus is yet to be investigated. Herein, we prepared silica cross-linked micelles (SCLMs) with a long blood circulation half-life as drug carriers to target the thrombus through passive targeting. Compared with SCLMs modified with an active targeting ligand cRGD, the SCLMs exhibited similar targeting behavior to the thrombus in vivo. Loaded with the thrombolytic drug tirofiban, the passive targeting SCLMs showed a comparable therapeutic effect to cRGD-modified SCLMs in a mice model with pulmonary embolism and arterial thrombosis.

Colorimetric discrimination and spectroscopic detection of tyrosine enantiomers based on melamine induced aggregation of l-cysteine/Au nanoparticles.

Au nanoparticles (AuNPs) are decorated by l-cysteine (L-Cys), and the resultant chiral L-Cys/AuNPs can be used for colorimetric discrimination and spectroscopic detection of the tyrosine (Tyr) enantiomers. Melamine (Mel) can induce the aggregation of the L-Cys/AuNPs through ligand exchange, leading to a distinct color change from wine red to purple. Owing to the same rotatory direction of L-Cys/AuNPs and L-Tyr, the L-Cys/AuNPs exhibit a significantly higher binding affinity toward L-Tyr than D-Tyr, and thus the Mel induced aggregation of the L-Cys/AuNPs is greatly alleviated by the protection from the L-Tyr protective layer. Therefore, the Tyr enantiomers can be simply discriminated by naked eyes. In addition, the absorbance of the aggregated L-Cys/AuNPs at ∼630 nm increases linearly with decreasing concentrations of L-Tyr ranging from 10 nM to 1 mM due to the weakened protection effect from L-Tyr, and thus spectroscopic detection of L-Tyr can also be accomplished by the developed L-Cys/AuNPs with a limit of detection (LOD) of 5.3 nM.

A Liquid-Liquid Interfacial Strategy for Construction of Electroactive Chiral Covalent-Organic Frameworks with the Aim to Enlarge the Testing Scope of Chiral Electroanalysis.

Although electroactive chiral covalent-organic frameworks (CCOFs) are considered an ideal platform for chiral electroanalysis, they are rarely reported due to the difficult selection of suitable precursors. Here, a facile strategy of liquid-liquid interfacial polymerization was carried out to synthesize the target electroactive CCOFs Ph-Py+-(S,S)-DPEA·PF6- and Ph-Py+-(R,R)-DPEA·PF6-. That is, a trivalent Zincke salt (4,4',4″-(benzene-1,3,5-triyl)tris(1-(2,4-dinitrophenyl)pyridin-1-ium)) trichloride (Ph-Py+-NO2) and enantiopure 1,2-diphenylethylenediamine (DPEA) were dissolved in water and chloroform, respectively. The Zincke reaction occurs at the interface, resulting in uniform porosity. As expected, the cyclic voltammetry and differential pulse voltammetry measurements showed that the tripyridinium units of the CCOFs afforded obvious electrochemical responses. When Ph-Py+-(S,S)-DPEA·PF6- was modified onto the surface of a glassy carbon electrode as a chiral sensor, the molecules, which included tryptophan, aspartic acid, serine, tyrosine, glutamic acid, mandelic acid, and malic acid, were enantioselectively recognized in the response of the peak current. Very importantly, the discriminative electrochemical signals were derived from Ph-Py+-(S,S)-DPEA·PF6-. The best peak current ratios between l- and d-enantiomers were in the range of 1.31-2.68. Besides, a good linear relationship between peak currents and enantiomeric excess (ee) values was established, which was successfully harnessed to determine the ee values for unknown samples. In a word, the current work provides new insight and potential of electroactive CCOFs for enantioselective sensing in a broad range.

A Highly Active Porous Mo2C-Mo2N Heterostructure on Carbon Nanowalls/Diamond for a High-Current Hydrogen Evolution Reaction.

Developing non-precious metal-based electrocatalysts operating in high-current densities is highly demanded for the industry-level electrochemical hydrogen evolution reaction (HER). Here, we report the facile preparation of binder-free Mo2C-Mo2N heterostructures on carbon nanowalls/diamond (CNWs/D) via ultrasonic soaking followed by an annealing treatment. The experimental investigations and density functional theory calculations reveal the downshift of the d-band center caused by the heterojunction between Mo2C/Mo2N triggering highly active interfacial sites with a nearly zero ∆GH* value. Furthermore, the 3D-networked CNWs/D, as the current collector, features high electrical conductivity and large surface area, greatly boosting the electron transfer rate of HER occurring on the interfacial sites of Mo2C-Mo2N. Consequently, the self-supporting Mo2C-Mo2N@CNWs/D exhibits significantly low overpotentials of 137.8 and 194.4 mV at high current densities of 500 and 1000 mA/cm2, respectively, in an alkaline solution, which far surpass the benchmark Pt/C (228.5 and 359.3 mV) and are superior to most transition-metal-based materials. This work presents a cost-effective and high-efficiency non-precious metal-based electrocatalyst candidate for the electrochemical hydrogen production industry.