YWHAG promotes colorectal cancer progression by regulating the CTTN-Wnt/ß-catenin signaling axis.

Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/ß-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/ß-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.

Reprogramming tumor-associated macrophages by a dually targeted milk exosome system as a potent monotherapy for cancer.

Tumor-associated macrophages (TAMs) play a key role in inducing an immunosuppressive tumor microenvironment (TME) and cancer immune escape. We previously revealed that PDL1 (a key immune checkpoint) was upregulated in TAMs and induced M2 polarization, highlighting PDL1 in TAMs as a promising cancer therapeutic target. In this study, we developed an engineered milk exosome (mExo) system decorated with M2pep (an M2 macrophage binding peptide) and 7D12 (an anti-EGFR nanobody) (7D12-mExo-M2pep-siPDL1) to specifically deliver siPDL1 into M2 TAMs. A series of in vitro and in vivo assays showed that the dually targeted engineered mExos efficiently delivered siPDL1 into M2 TAMs and repolarized them into M1 macrophages, restoring CD8+ T cell immune activity and remodeling TME. Importantly, systemically administered 7D12-mExo-M2pep-siPDL1 showed efficient single-agent antitumor activity, resulting in nearly 90% tumor growth inhibition in a mouse model of orthotopic epidermal growth factor receptor (EGFR) cancer. Collectively, our study indicates that PDL1 is a promising target for TAM-based cancer immunotherapy, and our engineered mExo-based nanomedicine represents a novel tool for specifically targeting M2 TAMs, distinguishing this novel therapeutic method from other TAM-targeting therapies and highlighting its promising clinical potential.

A method for extraction of exosomes from breast tumour cells and characterisation by transmission electron microscopy.

Exosomes can not only be used as markers of tumour metastasis but also be used for noninvasive diagnosis of clinical diseases, which holds significant medical research value. Observing the morphology and distribution of exosomes using transmission electron microscopy (TEM) is highly significant. In this study, we use breast tumour cell (MDA-MB-231) exosomes as a representative sample and focus on the extraction and purification of exosomes, as well as the investigation of optimal conditions for the observation of exosomes using TEM. Through comparative tests, we obtained the optimal dilution concentration and staining method for TEM of exosomes, the best dilution concentration is 100 times, the best negative staining time is 1.5 min. Western blotting and scanning electron microscopy (SEM) confirmed the presence of exosome. The particle size experiment shows that the size of exosomes is mainly distributed between 60 nm and 150 nm. This method provides a reference for TEM sample preparation of subcellular structures and small molecular biomaterials other than exosomes.

Clinical Report of a Rare Mucinous Staphylococcus Aureus Infection.

BACKGROUND: Staphylococcus aureus is the most common pathogen in suppurative infection, which can cause local suppurative infection, pneumonia, etc. A case of double renal calculi complicated with chronic renal insufficiency and mucinous Staphylococcus aureus infection was analyzed and discussed. METHODS: Bacterial culture, identification, and next-generation sequencing. RESULTS: The mucous colony was identified as Staphylococcus aureus, and the condition improved after symptomatic treatment. CONCLUSIONS: Mucinous Staphylococcus is a rare clinical microorganism, which needs to be verified by experiments to avoid false negative results. Genetic sequencing is used to identify strains if necessary.

PoolNet+: Exploring the Potential of Pooling for Salient Object Detection.

We explore the potential of pooling techniques on the task of salient object detection by expanding its role in convolutional neural networks. In general, two pooling-based modules are proposed. A global guidance module (GGM) is first built based on the bottom-up pathway of the U-shape architecture, which aims to guide the location information of the potential salient objects into layers at different feature levels. A feature aggregation module (FAM) is further designed to seamlessly fuse the coarse-level semantic information with the fine-level features in the top-down pathway. We can progressively refine the high-level semantic features with these two modules and obtain detail enriched saliency maps. Experimental results show that our proposed approach can locate the salient objects more accurately with sharpened details and substantially improve the performance compared with the existing state-of-the-art methods. Besides, our approach is fast and can run at a speed of 53 FPS when processing a 300 ×400 image. To make our approach better applied to mobile applications, we take MobileNetV2 as our backbone and re-tailor the structure of our pooling-based modules. Our mobile version model achieves a running speed of 66 FPS yet still performs better than most existing state-of-the-art methods. To verify the generalization ability of the proposed method, we apply it to the edge detection, RGB-D salient object detection, and camouflaged object detection tasks, and our method achieves better results than the corresponding state-of-the-art methods of these three tasks. Code can be found at http://mmcheng.net/poolnet/.

Ratiometric fluorescence sensing of formaldehyde in food samples based on bifunctional MOF.

A new fluorescence strategy was described for ratiometric sensing of formaldehyde (FA) with bifunctional MOF, which acted as a fluorescence reporter as well as biomimetic peroxidase. With the assistance of H2O2, NH2-MIL-101 (Fe) catalyzes the oxidation of non-luminescent substrate o-phenylenediamine (OPD) to produce fluorescent product (oxOPD) with the maximum emission at 570 nm. Besides, intrinsic fluorescence of MOF (λem = 445 nm) was quenched by oxOPD through inner filter effect (IFE). However, FA and OPD reacted to generate Schiff bases, which competitively consumed OPD inhibiting the generation of oxOPD. Under the excitation wavelength of 375 nm, a ratiometric strategy was designed to detect FA with the fluorescence intensity ratio at 445 nm and 570 nm (F445/F570) as readout signal. This strategy exhibited a wide linear range (0.1-50 µM) and low detection limit of 0.03 µM. This method was confirmed for FA detection in food samples. In addition to establishing a new method to detect FA, this work will open new applications of MOF in food safety.

Enhanced detection of ascorbic acid with cascaded fluorescence recovery of a dual-nanoquencher system.

An innovative strategy with target-triggered cascade fluorescence recovery of a dual-nanoquencher system was developed to detect ascorbic acid (AA). Herein, manganese dioxide (MnO2) nanosheets and gold nanoparticles (AuNPs) were used as nanoquenchers simultaneously. Owing to their synergistic effects, the fluorescence of 2,3-diaminophenazine (DAP) was decreased efficiently, thus minimizing the background fluorescence. The introduction of AA triggered the decomposition of MnO2 into Mn2+, which induced the aggregation of AuNPs. Both the decomposed MnO2 and aggregated AuNPs possess weak quenching abilities towards DAP. Such a cascade amplification strategy enhanced the detection sensitivity for AA with a LOD as low as 6.7 nM, which was two orders of magnitude lower than that of MnO2-based fluorescence assay. Furthermore, this amplification strategy was successfully applied to detect AA in food samples.

Nifuroxazide in combination with CpG ODN exerts greater efficacy against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumour in China that remains a major challenge to the medical community, and effective treatment is urgently needed. Due to complex tumorigenesis, monotherapy shows poor therapeutic effects, and combined treatment becomes a necessary option. YW002, a CpG ODN-containing sequence, has been proven to enhance antitumor effects in tumour-bearing mouse models. Moreover, as a broad-spectrum antimicrobial drug, nifuroxazide exhibited an anti-HCC effect through activation of p-Stat3. Here, we tested the effect of nifuroxazide on HCC in vitro and then explored the therapeutic effect of combined nifuroxazide and CpG ODN on HCC in vivo. Nifuroxazide inhibited proliferation, induced apoptosis and suppressed migration and invasion in HepG2 cells in vitro. The combination therapy using nifuroxazide and CpG ODN significantly suppressed the growth of tumours in tumour-bearing mice with few side effects and achieved better therapeutic effects on HCC than monotherapy. Moreover, combined nifuroxazide and CpG ODN therapy significantly induced apoptosis, enhanced the infiltration of CD4+ and CD8+ T lymphocytes and macrophages in tumour tissue, and increased the ratio of CD4+ and CD8+ T lymphocytes in the spleens of tumour-bearing mice. The introduction of this combination therapy combining nifuroxazide and CpG ODN provided a new strategy for HCC treatment.

High expression of CD28 enhanced the anti-cancer effect of siRNA-PD-1 through prompting the immune response of melanoma-bearing mice.

Immune checkpoint blockade is considered to be an effective method of tumor immunotherapy. As one of the main immune checkpoints, blocking PD-1/PD-L1 pathway has been proved to be effective in the treatment of many cancers via activating T cells; however, many patients still do not respond to the blocking PD-1/PD-L1 treatment with satisfying results. Related research demonstrated that the activation of T cells required a co-stimulatory signal generated by the interaction between CD28 and CD80/CD86, whereas in many patients, CD28 on the T cell surface was lost. Thus, in this study, we constructed the co-expression plasmid of CD28-siRNA-PD-1 and explored the anti-tumor mechanism of the co-expression plasmid on mouse model. The results showed that the expression of PD-1 was inhibited and the expression of CD28 was increased significantly in tumor tissues after the mice were treated with the co-expression plasmid. The survival rate of the tumor-bearing mice was recorded every day. PD-1 expression and tumor-infiltrating lymphocytes in cancer tissues were detected by immunofluorescence staining and the ratios of different immune cells in spleens were detected by flow cytometry. We found that treatment with the co-expression plasmid significantly prolonged the survival of melanoma-bearing mice, induced the cell apoptosis, increased the infiltration of T cells in tumor tissues, and altered the ratios of different immune cells in the spleens. These results also laid the foundation for reducing the resistance of PD-1 blockade in the clinic.

A novel polypeptide vaccine and adjuvant formulation of EV71.

Hand foot and mouth disease (HFMD) is an infectious disease mainly caused by Enterovirus 71 (EV 71). However, the effective treatment is limited currently. The aim of this study was to investigate the activity of the vaccine including the EV71 polypeptides mixed with a novel adjuvant containing CpG oligodeoxynucleotides (CpG ODNs). After collecting mouse sera, we determined the antibody concentration in serum by enzyme-linked immunosorbent assays (ELISA). Then, CD19+CD27+ B cells in the spleen were analysed by flow cytometry. The assay revealed that a substantial increase in antibody titers was achieved. This indicates a high level of immunogenicity for peptide vaccine and the good stability of adjuvant, also suggests that the combination of vaccine and adjuvant can stimulate the production of high-level antibodies and CD19+CD27+ B lymphocytes in mice. Furthermore, the antibody could effectively identify EV71 inactivated virus. The results demonstrated that the autonomous construction of EV71 polypeptide vaccine had a good immunogenicity. Moreover, the peptide vaccine injection with a novel adjuvant, which is easy to prepare, could cause a high antibody level of EV71 and shown a good application prospect.

D-MT prompts the anti-tumor effect of oxaliplatin by inhibiting IDO expression in a mouse model of colon cancer.

Colon cancer is one of the most common malignant tumors in the digestive system. Although oxaliplatin, a chemotherapy drug, has been clinically used to treat colon cancer, its therapeutic effect is unsatisfactory. It has been proved that indoleamine dioxygenase 2,3 (IDO) is a tumor immunosuppressive factor for the immune response. Herein, an IDO inhibitor, D-MT (indoximod, 1-Methyl-D-tryptophan), was combined with oxaliplatin to treat colon cancer in mice. T cell infiltration in tumor tissues, the ratios of immune cells in the spleens, and the tumor growth and survival of the mice were detected and recorded. The results showed that the combination of oxaliplatin and D-MT significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. More importantly, the combination treatment increased the ratios of CD4+ T, CD8+ T and NK cells from the spleen in tumor-bearing mice, and prompted T cell infiltration in tumor tissues. This study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance.

Rethinking the U-Shape Structure for Salient Object Detection.

The U-shape structure has shown its advantage in salient object detection for efficiently combining multi-scale features. However, most existing U-shape-based methods focused on improving the bottom-up and top-down pathways while ignoring the connections between them. This paper shows that we can achieve the cross-scale information interaction by centralizing these connections, hence obtaining semantically stronger and positionally more precise features. To inspire the newly proposed strategy's potential, we further design a relative global calibration module that can simultaneously process multi-scale inputs without spatial interpolation. Our approach can aggregate features more effectively while introducing only a few additional parameters. Our approach can cooperate with various existing U-shape-based salient object detection methods by substituting the connections between the bottom-up and top-down pathways. Experimental results demonstrate that our proposed approach performs favorably against the previous state-of-the-arts on five widely used benchmarks with less computational complexity. The source code will be publicly available.

PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer.

The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated Salmonella. Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of in vivo experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated Salmonella carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.

Identifying Diabetic Macular Edema and Other Retinal Diseases by Optical Coherence Tomography Image and Multiscale Deep Learning.

PURPOSE: Diabetic Macular Edema has been one of the research hotspots all over the world. But as the global population continues to grow, the number of OCT images requiring manual analysis is becoming increasingly unaffordable. Medical images are often fuzzy due to the inherent physical processes of acquiring them. It is difficult for traditional algorithms to use low-quality data. And traditional algorithms usually only provide diagnostic results, which makes the reliability and interpretability of the model face challenges. To solve problem above, we proposed a more intuitive and robust diagnosis model with self-enhancement ability and clinical triage patients' ability. METHODS: We used 38,057 OCT images (Drusen, DME, CNV and Normal) to establish and evaluate the model. All data are OCT images of fundus retina. There were 37,457 samples in the training dataset and 600 samples in the validation dataset. In order to diagnose these images accurately, we propose a multiscale transfer learning algorithm. Firstly, the sample is sent to the automatic self-enhancement module for edge detection and enhancement. Then, the processed data are sent to the image diagnosis module to determine the disease type. This process makes more data more effective and can be accurately classified. Finally, we calculated the accuracy, precision, sensitivity and specificity of the model, and verified the performance of the model from the perspective of clinical application. RESULTS: The model proposed in this paper can provide the diagnosis results and display the detection targets more intuitively. The model reached 94.5% accuracy, 97.2% precision, 97.7% sensitivity and 97% specificity in the independent testing dataset. CONCLUSION: Comparing the performance of relevant work and ablation test, our model achieved relatively good performance. It is proved that the model proposed in this paper has a stronger ability to recognize diseases even in the face of low-quality images. Experiment results also demonstrate its clinical referral capability. It can reduce the workload of medical staff and save the precious time of patients.

Seed-Morphology-Directed Synthesis of Concave Gold Nanocrystals with Tunable Sizes.

We report the fabrication of concave gold (Au) nanocrystals with a set of morphologies and controlled sizes via seeded growth. Starting with Au seeds with a well-defined morphology and uniform size, cubic and rodlike Au nanocrystals with a noticeable concave feature could be successfully obtained, respectively. We also track the growth process and record the shape evolution process. The effect of several reaction parameters on product morphology, such as capping agent and concentration of Ag+, are systematically investigated. Their optical and electrochemical properties are investigated via UV-vis extinction spectroscopy and cyclic voltammetry, respectively. Compared to spherical counterparts, the current concave Au nanocrystals exhibit a noticeable red shift of the absorbance peak in UV-vis extinction spectra and characterized electrochemical behavior of stepped facets, illustrating the morphological advantage.

Deep Learning-Based Method of Diagnosing Hyperlipidemia and Providing Diagnostic Markers Automatically.

INTRODUCTION: The research of auxiliary diagnosis has always been one of the hotspots in the world. The implementation of auxiliary diagnosis support algorithm for medical text data faces challenges with interpretability and creditability. The improvement of clinical diagnostic techniques means not only the improvement of diagnostic accuracy but also the further study of diagnostic basis. Traditional research methods for diagnostic markers often require a large amount of time and economic costs. Research objects are often dozens of samples, and it is, therefore, difficult to synthesize large amounts of data. Therefore, the comprehensiveness and reliability of traditional methods have yet to be improved. Therefore, the establishment of a model that can automatically diagnose diseases and automatically provide a diagnostic basis at the same time has a positive effect on the improvement of medical diagnostic techniques. METHODS: Here, we established an auxiliary diagnostic tool based on attention deep learning algorithm to diagnostic hyperlipemia and automatically predict the corresponding diagnostic markers using hematological parameters. In this paper, we not only demonstrated the ability of the proposed model to automatically diagnose diseases using text-based medical data, such as physiological parameters, but also demonstrated its ability to forecast disease diagnostic markers. Human physiological parameters are used as input to the model, and the doctor's diagnosis results as an output. Through the attention layer, the degree of attention of the model to different physiological parameters can be obtained, that is, the model provides a diagnostic basis. RESULTS: It achieved 94% ACC, 97.48% AUC, 96% sensitivity and 92% specificity with the test dataset. All the above samples are drawn from clinical practice. Moreover, the model predicted the diagnostic markers of hyperlipidemia by the attention mechanism, and the results were fully agreeable to the golden criteria. DISCUSSION: The auxiliary diagnosis system proposed in this paper not only achieves the accurate and robust performance, and can be used for the preliminary diagnosis of patients, but also showing its great potential to discover new diagnostic markers. Therefore, it not only can improve the efficiency of clinical diagnosis but also shorten the research period of researching a diagnosis basis to an extent. It has a positive significance to the development of the medical diagnosis level.

Effect of miR-135b inhibitor on biological characteristics of osteosarcoma cells through up-regulating PPM1A.

miR-135b is expressed abnormally in various tumors and plays an important role in the occurrence and development of tumors bydifferent pathways. The role of miR-135b in osteosarcoma (OS) and its mechanisms were uncertain. The study aimed to clarify the role of miR-135b in osteosarcoma (OS) cells and explore the effect of miR-135b inhibitor on the biological characteristics of OS cells. Firstly, Compared with adjacent bone tissues, the expression of miR-135b was increased and inversely correlated with potential target-PPM1A mRNA, while the expression of PPM1A was decreased in OS tissues. Dual luciferase reporter assay was used to verify that PPM1A was a target gene of miR-135b and RT-PCR and western blot were used to detect that miR-135b negatively regulated expression of PPM1A in MG63 and U2OS cell lines. After transfection, miR-135b inhibitor significantly inhibited cell proliferation and invasion both in MG63 and U2OS cells and blocked cell cycle in the G2/M phase and induced cells apoptosis, while PPM1A knockdown abolished the inhibition of miR-135b inhibitor on the proliferation and invasion of OS cells. In conclusion, miR-135b is up-regulated in OS cells and down regulating miR-135b expression could inhibit the proliferation and invasion of OS cells by up-regulating PPM1A. miR-135b might be a new therapeutic target of OS.

[Correlation analysis between interleukin 6 polymorphism and adolescent idiopathic scoliosis susceptibility and bracing effectiveness].

Objective: To analyze the correlation between the polymorphism on interleukin 6 (IL-6) gene promoter region-174 locus and adolescent idiopathic scoliosis (AIS), including the susceptibility, the bracing effectiveness, and the possible mechanism. Methods: The 182 AIS patients and 210 healthy controls who met the inclusion criteria between January 2013 and January 2016 were collected as research objects. The genotype of IL-6 gene promoter region-174 locus, the serum IL-6, the bone mineral density (BMD) of femoral neck and vertebrae (L 1-4), and the bone metabolism parameters, including bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate resistant acid phosphatase 5b (TRACP-5b), urine Ca, and urine Ca/Cr, were detected. All research objects were divided into the AIS group and the control group according to whether they had AIS, the GG, CG, CC groups according to their genotype, and progression-free group and progression group according to the therapeutic effectiveness of 1-year bracing treatment. Statistical analysis for the indexes were conducted respectively. Results: There were significant differences in AIS history, BMD of femoral neck and lumbar vertebrae between the AIS group and control group ( P<0.05). According to the therapeutic effecitveness of 1-year bracing treatment, 182 AIS patients were divided into progression-free group in 110 cases and progression group in 72 cases. The results of single factor analysis showed that there were significant differences in the genotype and allele distribution of IL-6 gene promoter region-174 locus, BMD of femoral neck and lumbar vertebrae, IL-6, TRACP-5b, urine Ca, and urine Ca/Cr between the progression-free group and progression group ( P<0.05). The results of multivariable analysis showed that the BMD of lumbar vertebrae, TRACP-5b, and urine Ca were the influencing factors of bracing efficacy ( P<0.05). According to the results of genotype detection, all research objects were divided into GG group in 264 cases, CG group in 104 cases, and CC group in 24 cases. The IL-6, TRACP-5b, urine Ca, and urine Ca/Cr of GG type carriers were higher and BMD of femoral neck and lumbar vertebrae were lower when compared with the CG and CC type carriers ( P<0.05). The BMD of lumbar vertebrae of CG type carriers was lower than that of CC type carriers ( P<0.05). Conclusion: The polymorphism of IL-6 genepromoter region-174 locus wasn't correlated with the AIS susceptibility, but it was correlated (not independently correlated) with the scoliosis progression under bracing treatment, and the risk for G-carried patients was higher. The mechanism may be that the polymorphism affected the IL-6 expression level and eventually affected the BMD of AIS patients through the bone metabolism.

In situ development of amorphous Mn-Co-P shell on MnCo2O4 nanowire array for superior oxygen evolution electrocatalysis in alkaline media.

Exploitation of efficient and earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is of great importance. Herein, we report that the formation of an amorphous Mn-Co-P shell on MnCo2O4 can boost its OER activity in alkaline media. The core-shell Mn-Co-P@MnCo2O4 nanowire array on Ti mesh (Mn-Co-P@MnCo2O4/Ti) shows excellent electrochemical catalytic activity and requires an overpotential of 269 mV to drive 10 mA cm-2 in 1.0 M KOH, which is 93 mV less than that for the MnCo2O4 nanoarray. Notably, this catalyst also shows strong long-term electrochemical durability with its activity being maintained for at least 100 h and achieves a high turnover frequency of 1.06 s-1 at an overpotential of 450 mV.

Co(OH)2 Nanoparticle-Encapsulating Conductive Nanowires Array: Room-Temperature Electrochemical Preparation for High-Performance Water Oxidation Electrocatalysis.

It is highly desired but still remains challenging to design and develop a Co-based nanoparticle-encapsulated conductive nanoarray at room temperature for high-performance water oxidation electrocatalysis. Here, it is reported that room-temperature anodization of a Co(TCNQ)2 (TCNQ = tetracyanoquinodimethane) nanowire array on copper foam at alkaline pH leads to in situ electrochemcial oxidation of TCNQ- into water-insoluable TCNQ nanoarray embedding Co(OH)2 nanoparticles. Such Co(OH)2 -TCNQ/CF shows superior catalytic activity for water oxidation and demands only a low overpotential of 276 mV to drive a geometrical current density of 25 mA cm-2 in 1.0 m KOH. Notably, it also demonstrates strong long-term electrochemical durability with its activity being retrained for at least 25 h, a high turnover frequency of 0.97 s-1 at an overpotential of 450 mV and 100% Faradic efficiency. This study provides an exciting new method for the rational design and development of a conductive TCNQ-based nanoarray as an interesting 3D material for advanced electrochemical applications.