Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct expression patterns and potential markers of progression.

In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies. Significance: This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.

Disruption of the peripheral biological clock may play a role in sleep deprivation-induced dysregulation of lipid metabolism in both the daytime and nighttime phases.

STUDY OBJECTIVES: This study aimed to examine the effect of sleep deprivation (SD) on lipid metabolism or lipid metabolism regulation in the liver and white adipose tissue (WAT) during the light and dark phases and explored the possible mechanisms underlying the diurnal effect of SD on lipid metabolism associated with clock genes. METHODS: Male C57BL/6J mice aged 2 months were deprived of sleep daily for 20 h for ten consecutive days with weakly forced locomotion. The body weights and food consumption levels of the SD and control mice were recorded, and the mice were then sacrificed at ZT (zeitgeber time) 2 and ZT 14. The peripheral clock genes, enzymes involved in fat synthesis and catabolism in the WAT, and melatonin signalling pathway-mediated lipid metabolism in the liver were assessed. Untargeted metabolomics and tandem mass tag (TMT) proteomics were used to identify differential lipid metabolism pathways in the liver. RESULTS: Bodyweight gain and daily food consumption were dramatically elevated after SD. Profound disruptions in the diurnal regulation of the hepatic peripheral clock and enzymes involved in fat synthesis and catabolism in the WAT were observed, with a strong emphasis on hepatic lipid metabolic pathways, while melatonin signalling pathway-mediated lipid metabolism exhibited moderate changes. CONCLUSIONS: In mice, ten consecutive days of SD increased body weight gain and daily food consumption. In addition, SD profoundly disrupted lipid metabolism in the WAT and liver during the light and dark periods. These diurnal changes may be related to disorders of the peripheral biological clock.

Ultra-sensitive electrochemical sensor based on in situ grown ultrafine HKUST-1 nanoparticles @ graphite nanosheets and core-shell structured MoO3-polypyrrole nanowires for the detection of rutin in orange juice.

Rutin extracted from natural plants has important medical value, so developing accurate and sensitive quantitative detection methods is one of the most important tasks. In this work, HKUST-1@GN/MoO3-Ppy NWs were utilized to develop a high-performance rutin electrochemical sensor in virtue of its high conductivity and electrocatalytic activity. The morphology, crystal structure, and chemical element composition of the fabricated sensor composites were characterized by SEM, TEM, XPS, and XRD. Electrochemical techniques including EIS, CV, and DPV were used to investigate the electrocatalytic properties of the prepared materials. The electrochemical test conditions were optimized to achieve efficient detection of rutin. The 2-electron 2-proton mechanism, consisting of several rapid and sequential phases, is postulated to occur during rutin oxidation. The results show that HKUST-1@GN/MoO3-Ppy NWs have the characteristics of large specific surface area, excellent conductivity, and outstanding electrocatalytic ability. There is a significant linear relationship between rutin concentration and the oxidation peak current of DPV. The linear range is 0.50-2000 nM, and the limit of detection is 0.27 nM (S/N = 3). In addition, the prepared electrode has been confirmed to be useful for rutin analysis in orange juice.

METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression.

Without intervention, a considerable proportion of patients with metabolism-associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism-associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1+Ccr2+ monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1+Ccr2+ Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1+Ccr2+ Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

A multi-tissue metabolome atlas of primate pregnancy.

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.

Frozen tissue coring and layered histological analysis improves cell type-specific proteogenomic characterization of pancreatic adenocarcinoma.

BACKGROUND: Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and potential benefit of using a coring method to enrich specific regions from bulk tissue and then perform proteogenomic analyses. METHODS: We used the Biopsy Trifecta Extraction (BioTExt) technique to isolate cores of epithelial-enriched and stroma-enriched tissue from pancreatic tumor and adjacent tissue blocks. Histology was assessed at multiple depths throughout each core. DNA sequencing, RNA sequencing, and proteomics were performed on the cored and bulk tissue samples. Supervised and unsupervised analyses were performed based on integrated molecular and histology data. RESULTS: Tissue cores had mixed cell composition at varying depths throughout. Average cell type percentages assessed by histology throughout the core were better associated with KRAS variant allele frequencies than standard histology assessment of the cut surface. Clustering based on serial histology data separated the cores into three groups with enrichment of neoplastic epithelium, stroma, and acinar cells, respectively. Using this classification, tumor overexpressed proteins identified in bulk tissue analysis were assigned into epithelial- or stroma-specific categories, which revealed novel epithelial-specific tumor overexpressed proteins. CONCLUSIONS: Our study demonstrates the feasibility of multi-omics data generation from tissue cores, the necessity of interval H&E stains in serial histology sections, and the utility of coring to improve analysis over bulk tissue data.

Mordo2: A Personalization Framework for Silent Command Recognition.

Wearable human-computer interactions in daily life are increasingly encouraged by the prevalence of intelligent wearables. It poses a demanding requirement of micro-interaction and minimizing social awkwardness. Our previous work demonstrated the feasibility of recognizing silent commands through around-ear biosensors with the limitation of user adaptation. In this work, we ease the limitation by a personalization framework that integrates spectral factorization of signals, temporal confidence rejection and commonly used transfer learning algorithms. Specifically, we first empirically formulate the user adaptation issue by presenting the accuracies of applying transfer learning algorithms to our previous method. Second, we improve the signal-to-noise ratio by proposing the supervised spectral factorization method that learns the amplitude and phase mappings between around-ear signals and the signals of articulated facial muscles. Third, we leverage the time continuity of commands and introduce the time decay into confidence rejection. Finally, extensive experiments have been conducted to evaluate the feasibility and improvements. The results indicate an average accuracy of 92.38% which is significantly larger than solely using transfer learning algorithms. And a comparable accuracy can be achieved with significantly reduced data of new users. The overall performance shows the framework can significantly improve the accuracy of user adaptations. The work would aid a further step toward commercial products for silent command recognition and inspire the solution to the user adaptation challenge of wearable human-computer interactions.

Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma.

Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial-mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs. SIGNIFICANCE: The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors.

Gender dimorphism in hepatocarcinogenesis-DNA methylation modification regulated X-chromosome inactivation escape molecule XIST.

BACKGROUND: Sex disparities constitute a significant issue in hepatocellular carcinoma (HCC). However, the mechanism of gender dimorphism in HCC is still not completely understood. METHODS: 5-Hydroxymethylcytosine (5hmC)-Seal technology was utilised to detect the global 5hmC levels from four female and four male HCC samples. Methylation of XIST was detected by Sequenom MassARRAY methylation profiling between HCC tissues (T) and adjacent normal liver tissues (L). The role of Tet methylcytosine dioxygenase 2 (TET2) was investigated using diethylnitrosamine (DEN)-administered Tet2-/- female mice, which regulated XIST in hepatocarcinogenesis. All statistical analyses were carried out by GraphPad Prism 9.0 and SPSS version 19.0 software. RESULTS: The results demonstrated that the numbers of 5hmC reads in the first exon of XIST from female HCC tissues (T) were remarkably lower than that in female adjacent normal liver tissues (L). Correspondingly, DNA methylation level of XIST first exon region was significantly increased in female T than in L. By contrast, no significant change was observed in male HCC patients. Compared to L, the expression of XIST in T was also significantly downregulated. Female patients with higher XIST in HCC had a higher overall survival (OS) and more extended recurrence-free survival (RFS). Moreover, TET2 can interact with YY1 binding to the promoter region of XIST and maintain the hypomethylation state of XIST. In addition, DEN-administered Tet2-/- mice developed more tumours than controls in female mice. CONCLUSIONS: Our study provided that YY1 and TET2 could interact to form protein complexes binding to the promoter region of XIST, regulating the methylation level of XIST and then affecting the expression of XIST. This research will provide a new clue for studying sex disparities in hepatocarcinogenesis. HIGHLIGHTS: XIST was significantly downregulated in HCC tissues and had gender disparity. Methylation levels in the XIST first exon were higher in female HCC tissues, but no significant change in male HCC patients. The TET2-YY1 complex regulate XIST expression in female hepatocytes. Other ways regulate XIST expression in male hepatocytes.

Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state.

During homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a+Pax7- skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+ MuSC pool to drive muscle regeneration. Compared with adult Pax7+ MuSCs, Lin28a+ MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. The epigenome of adult Lin28a+ MuSCs showed resemblance to embryonic muscle progenitors. In addition, RNA-sequencing revealed that Lin28a+ MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7+ MuSCs, resulting in enhanced self-renewal and stress-response signatures. Functionally, conditional ablation and induction of Lin28a+ MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

Muscle Injuries Induce a Prostacyclin-PPARγ/PGC1a-FAO Spike That Boosts Regeneration.

It is well-known that muscle regeneration declines with aging, and aged muscles undergo degenerative atrophy or sarcopenia. While exercise and acute injury are both known to induce muscle regeneration, the molecular signals that help trigger muscle regeneration have remained unclear. Here, mass spectrometry imaging (MSI) is used to show that injured muscles induce a specific subset of prostanoids during regeneration, including PGG1, PGD2, and the prostacyclin PGI2. The spike in prostacyclin promotes skeletal muscle regeneration via myoblasts, and declines with aging. Mechanistically, the prostacyclin spike promotes a spike in PPARγ/PGC1a signaling, which induces a spike in fatty acid oxidation (FAO) to control myogenesis. LC-MS/MS and MSI further confirm that an early FAO spike is associated with normal regeneration, but muscle FAO became dysregulated during aging. Functional experiments demonstrate that the prostacyclin-PPARγ/PGC1a-FAO spike is necessary and sufficient to promote both young and aged muscle regeneration, and that prostacyclin can synergize with PPARγ/PGC1a-FAO signaling to restore aged muscles' regeneration and physical function. Given that the post-injury prostacyclin-PPARγ-FAO spike can be modulated pharmacologically and via post-exercise nutrition, this work has implications for how prostacyclin-PPARγ-FAO might be fine-tuned to promote regeneration and treat muscle diseases of aging.

XAI-enabled neural network analysis of metabolite spatial distributions.

We used deep neural networks to process the mass spectrometry imaging (MSI) data of mouse muscle (young vs aged) and human cancer (tumor vs normal adjacent) tissues, with the aim of using explainable artificial intelligence (XAI) methods to rapidly identify biomarkers that can distinguish different classes of tissues, from several thousands of metabolite features. We also modified classic neural network architectures to construct a deep convolutional neural network that is more suitable for processing high-dimensional MSI data directly, instead of using dimension reduction techniques, and compared it to seven other machine learning analysis methods' performance in classification accuracy. After ascertaining the superiority of Channel-ResNet10, we used a novel channel selection-based XAI method to identify the key metabolite features that were responsible for its learning accuracy. These key metabolite biomarkers were then processed using MetaboAnalyst for pathway enrichment mapping. We found that Channel-ResNet10 was superior to seven other machine learning methods for MSI analysis, reaching > 98% accuracy in muscle aging and colorectal cancer datasets. We also used a novel channel selection-based XAI method to find that in young and aged muscle tissues, the differentially distributed metabolite biomarkers were especially enriched in the propanoate metabolism pathway, suggesting it as a novel target pathway for anti-aging therapy.

Spatial metabolomics reveals skeletal myofiber subtypes.

Skeletal muscle myofibers are heterogeneous in their metabolism. However, metabolomic profiling of single myofibers has remained difficult. Mass spectrometry imaging (MSI) is a powerful tool for imaging molecular distributions. In this work, we optimized the workflow of matrix-assisted laser desorption/ionization (MALDI)-based MSI from cryosectioning to metabolomics data analysis to perform high-spatial resolution metabolomic profiling of slow- and fast-twitch myofibers. Combining the advantages of MSI and liquid chromatography-MS (LC-MS), we produced spatial metabolomics results that were more reliable. After the combination of high-spatial resolution MSI and LC-MS metabolomic analysis, we also discovered a new subtype of superfast type 2B myofibers that were enriched for fatty acid oxidative metabolism. Our technological workflow could serve as an engine for metabolomics discoveries, and our approach has the potential to provide critical insights into the metabolic heterogeneity and pathways that underlie fundamental biological processes and disease states.

The next "sweet" spot for pancreatic ductal adenocarcinoma: Glycoprotein for early detection.

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas, accounting for more than 90% of all pancreatic malignancies. As a highly lethal malignancy, PDAC is the fourth leading cause of cancer-related deaths worldwide with a 5-year overall survival of less than 8%. The efficacy and outcome of PDAC treatment largely depend on the stage of disease at the time of diagnosis. Surgical resection followed by adjuvant chemotherapy remains the only possibly curative therapy, yet 80%-90% of PDAC patients present with nonresectable PDAC stages at the time of clinical presentation. Despite our advancing knowledge of PDAC, the prognosis remains strikingly poor, which is primarily due to the difficulty of diagnosing PDAC at the early stages. Recent advances in glycoproteomics and glycomics based on mass spectrometry have shown that aberrations in protein glycosylation plays a critical role in carcinogenesis, tumor progression, metastasis, chemoresistance, and immuno-response of PDAC and other types of cancers. A growing interest has thus been placed upon protein glycosylation as a potential early detection biomarker for PDAC. We herein take stock of the advancements in the early detection of PDAC that were carried out with mass spectrometry, with special focus on protein glycosylation.

Differentially expressed glycoproteins in pre- and post-digital rectal examination urine samples for detecting aggressive prostate cancer.

Urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) were previously reported using post-digital rectal examination (DRE) urine specimens. To explore the potential of using pre-DRE urine specimens for detecting AG-PCa, we compared glycoproteins between pre- and post-DRE urine specimens, verified the previously identified post-DRE AG-PCa-associated urinary glycoproteins in pre-DRE urine specimens, and explored potential new glycoproteins for AG-PCa detection in pre-DRE urine specimens. Quantitative glycoproteomic data were acquired for 154 pre-DRE urine specimens from 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score = 6), and 65 patients with AG-PCa (Gleason score 7 or above). Compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas cell mediated immune response proteins were enriched in post-DRE urine samples. Analyses of AG-PCa-associated glycoproteins from pre-DRE urine revealed that the three urinary glycoproteins, prostate-specific antigen (PSA), prostatic acid phosphatase (ACPP), and CD97 antigen (CD97) that were previously identified in post-DRE urine samples, were also observed as AG-PCa associated glycoproteins in pre-DRE urine. In addition, we identified three new glycoproteins, fibrillin 1 (FBN1), vitronectin (VTN), and hemicentin 2 (HMCN2), to be potentially associated with AG-PCa in pre-DRE urine specimens. In summary, glycoprotein profiles differ between pre- and post-DRE urine specimens. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant PCa.

Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness.

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.

Roles of RNA m6A modification in nonalcoholic fatty liver disease.

NAFLD is a series of liver disorders, and it has become the most prevalent hepatic disease to date. However, there are no approved and effective pharmaceuticals for NAFLD owing to a poor understanding of its pathological mechanisms. While emerging studies have demonstrated that m6A modification is highly associated with NAFLD. In this review, we summarize the general profile of NAFLD and m6A modification, and the role of m6A regulators including erasers, writers, and readers in NAFLD. Finally, we also highlight the clinical significance of m6A in NAFLD.

Melatonin protects against body weight gain induced by sleep deprivation in mice.

Sleep deprivation is an epidemic phenomenon in modern society. Lack of sleep has been shown to result in metabolic and endocrine disorders that predispose to obesity and other chronic metabolic diseases. Melatonin is a sleep-related neurohormone and affected by the circadian rhythm and light/dark cycles. Melatonin has recently been used to ameliorate diet-induced or night light-induced energy metabolic imbalance. However, the effect of melatonin on sleep deprivation-induced obesity has been poorly characterized. This study focuses on the protective effects of melatonin on lipid metabolism and body weight homeostasis in sleep-deprived mice. Mice subjected to sleep deprivation had significantly decreased plasma melatonin content and increased food intake and body weight gain compared to that of control. Meanwhile, the transcription factor PPARγ protein in liver increased, but there were no significant changes in hepatic circadian proteins BMAL1 and REV-ERBα after 10 consecutive days of sleep deprivation. Moreover, melatonin supplementation increased liver AMPKα/PPARα signaling pathway activity, which leads to lipid catabolism and reduced fat accumulation. These findings suggested that melatonin may be a potential agent for protecting against sleep deprivation-induced obesity.

Ultrasensitive catechin electrochemical sensor based on uniform ordered mesoporous carbon hollow spheres (MCHSs) advanced carbon-based conductive materials.

Catechin is one of the flavonoids with antioxidant activity and has attracted great interest. A rapid and accurate detection of catechin is of great significance. Herein, an ultrasensitive catechin electrochemical sensor based on uniform ordered mesoporous carbon hollow spheres (MCHSs) advanced carbon-based conductive material modified glass carbon electrode was constructed. The MCHSs were synthesized by pyrolysis using nitrogen protection and template removal methods, and they exhibited excellent electrochemical detection for catechin owing to their high conductivity and uniform and small spheres with a large specific surface area and hollow structure. Under optimal conditions for the detection of catechin, the MCHSs/GCE showed a wider linear range (10 -1400 nM) and lower detection limit (LOD, 2.82 nM, (S/N = 3)). Furthermore, the electrochemical reaction sites and redox mechanisms of catechin were revealed by electrochemical behavior and density flooding theory. Moreover, the sensor we constructed exhibited good accuracy and stability for the detection of catechin in actual sample detections.