Histone modifications underpin the cell-type-specific gene regulatory networks that drive the remarkable cellular heterogeneity of the adult mammalian brain. Here, we profiled four histone modifications jointly with transcriptome in 2.5 million nuclei across multiple adult mouse brain regions. By integrating these data with existing maps of chromatin accessibility, DNA methylation, and 3D genome organization, we established a unified regulatory framework for over 100 brain cell subclasses. This integrative epigenomic atlas annotates 81% of the genome, defining distinct active, primed, and repressive states. Notably, active chromatin states marked by combinatorial histone modifications more precisely identify functional enhancers than chromatin accessibility alone, while Polycomb- and H3K9me3-mediated repression contributes prominently to cell-type-specific regulation. Finally, this multi-modal resource enables deep learning models to predict epigenomic features and gene expression from DNA sequences. This work provides a comprehensive annotation of the mouse brain regulatory genome and a framework for interpreting non-coding variation in complex tissues.

Limited oxygen supply or hypoxia can impair fetal development and lead to developmental disorders, but the molecular mechanism underlying this phenomenon remains poorly understood. It is also well known that hypoxia results in transcriptomic alterations and epigenetic reprogramming. Drosophila melanogaster (fruit fly) has been used for decades as a powerful model to dissect the molecular mechanisms regulating development. To better understand the role of early hypoxic stress on development, we performed single-cell joint analysis of chromatin accessibility and transcriptome to characterize the influence of hypoxia on Drosophila embryonic development. We identified hypoxia-induced alterations in both gene expression and chromatin accessibility across 22 cell groups, especially in the genes regulating organogenesis and development of neuronal, tracheal, and muscular systems, including a reduction of germ cells, suggesting a long-lasting influence of hypoxic stress at an early embryonic stage on development and reproduction. In summary, this study demonstrates that early embryonic hypoxia induces cell type- and dose-dependent changes in chromatin accessibility and gene expression, leading to distinct developmental phenotypic responses, such as reduced number of germ cells under both 3% and 5% O₂. We further conclude that the tramtrack ( ttk ) gene is critical in germ cell development and reproduction in Drosophila melanogaster .

BACKGROUND:Intracranial solitary fibrous tumors (ISFTs) are frequently misdiagnosed as meningiomas on MRI. Existing MRI signs have been evaluated individually, without a standardized and externally validated diagnostic framework. PURPOSE:To develop and validate an MRI-based diagnostic score for intracranial solitary fibrous tumors (ISFT-DS) for the preoperative identification of ISFTs. STUDY TYPE:Retrospective multicenter diagnostic accuracy study. POPULATION:Five hundred with ISFTs (mean age, 46.4 ± 11.7 years; 269 men), 250 with low-grade meningiomas (mean age, 57.0 ± 11.1 years; 51 men), and 250 with high-grade meningiomas (mean age, 49.6 ± 14.3 years; 108 men). The development and external validation cohorts included 840 (84%) and 160 (16%) patients, respectively. FIELDSTRENGTH/SEQUENCE:Spin-echo T1-weighted imaging (T1WI), fast or turbo spin-echo T2-weighted imaging, and contrast-enhanced spin-echo T1-weighted imaging. ASSESSMENT:Three potential MRI features-T1WI hyperintensity, honeycomb-like cystic change, and trans-compartmental growth pattern-were assessed by three neuroradiologists and combined into the 0-3-point ISFT-DS. Diagnostic performance and the effects of standardized training in six readers were evaluated. STATISTICAL TESTS:Sensitivity, specificity, accuracy, kappa statistics, receiver operating characteristic analysis, DeLong tests, χ2and Fisher exact tests, analysis of variance, McNemar test, Kruskal-Wallis tests. p < 0.05 indicated statistical significance. RESULTS:At an ISFT-DS cutoff of ≥ 1, sensitivity/specificity were 81.4%/83.3% in the development cohort and 76.3%/86.3% in the external validation cohort, respectively. Specificity reached 98.3%/98.8% at ≥ 2 and 100%/100% at 3. Interreader agreement was good to excellent for the three MRI features and the ISFT-DS (κ = 0.80-0.87). Standardized reader training on the ISFT-DS increased the overall AUC from 0.67 to 0.80 (ΔAUC = 0.13), with larger gains for Readers 1 and 2 (ΔAUC = 0.21 and 0.15, respectively). DATA CONCLUSION:The ISFT-DS provides a reproducible and teachable MRI-based scoring system for standardized preoperative identification of ISFTs. EVIDENCE LEVEL:3. TECHNICAL EFFICACY:Stage 2.

Background:Primary angiosarcoma of bone (ASB) is a rare and aggressive primary bone tumor. The prognostic significance of anatomical location (axial vs. appendicular skeleton) remains poorly defined. This study aimed to compare clinicopathological features and survival outcomes between these two groups. Methods:Patients diagnosed with primary ASB (1975-2019) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Tumors were categorized as axial (spine, pelvis, ribs, skull) or appendicular (extremities). Overall survival was analyzed using Kaplan-Meier and Cox models. Cancer-specific mortality (CSM) was evaluated with Fine-Gray competing risk regression to calculate subdistribution hazard ratios (SHR). Results:Among 458 patients, 162 (35.4%) had axial and 296 (64.6%) had appendicular tumors. Axial patients were older (median 63 vs. 46 years, p < 0.001), had higher distant metastasis at diagnosis (43.2% vs. 29.1%, p = 0.002), and underwent surgery less frequently (37.0% vs. 81.1%, p < 0.001). The 5-year overall survival was significantly worse for axial tumors (16.8% vs. 38.2%, p < 0.001). The 5-year cumulative incidence of CSM was 69.5% for axial versus 50.8% for appendicular tumors (p < 0.001). Multivariate analysis confirmed axial location as an independent predictor of higher CSM (SHR 1.62, 95% CI: 1.25-2.10, p < 0.001) , independent of the year of diagnosis. Conclusions:Axial tumors represent a distinct high-risk subgroup characterized by limited surgical resectability and inferior survival. Anatomical location should be considered a critical stratification factor in clinical management and future trials.Abbreviations: ASB, Primary angiosarcoma of the bone; SEER, Surveillance, Epidemiology, and End Results; OS, Overall Survival; CSS, Cancer-Specific Survival; CSD, Cancer-Specific Death; CIF, Cumulative Incidence Function; SHR, Subdistribution Hazard Ratio; CI, Confidence Interval; HR, Hazard Ratio.

Integrating single-cell transcriptomic and epigenomic data provides a robust framework for investigating gene regulation mechanisms. Existing analyses typically treat these modalities as synchronized features that can be translated in a static manner; however, the temporal delays that underpin cellular kinetics are intrinsic to dynamic biological systems. To address this limitation, we propose utilizing the "molecular asynchrony" within regulatory hierarchies to determine the thermodynamic properties of individual cells. Here, we present SeqTag, a single-cell multiomics sequencing method that simultaneously profiles the transcriptome, chromatin accessibility, and histone modifications, supported by an analytical framework to identify asynchronous states across regulatory layers for characterization of single-cell kinetics. By measuring the epigenetic priming potential and remodeling rates during adult mouse oligodendrogenesis, we delineated a sequential program for bivalency resolution as maturing cells traverse Waddington's landscape. This process becomes increasingly decoupled with age, a change linked to a drift in progenitor cell-fate probabilities. By identifying entropy-driving regulatory elements, we characterized the aging-related decline in cell identity across various cell types and proposed a dynamic model linking static genetic variants to the risk of late-onset diseases. In summary, our integrated approach established a unified framework for employing multimodal single-cell genomics to model the kinetics of complex cellular processes.

The value of a deep learning (DL) model in distinguishing intracranial solitary fibrous tumors (ISFTs) from angiomatous meningiomas (AMs) and predicting overall survival (OS) of patients with ISFTs have not been systematically assessed. The aim of this study was to develop and validate an MRI-based DL model for distinguishing ISFTs from AMs and predicting OS for patients with ISFTs. (Transformer + Clinic) and clinical models were developed and validated on retrospectively collected preoperative MRI scans of patients with ISFTs and AMs diagnosed between January 2008 and January 2023 at primary cohort (PC) and external validation cohort (EVC). We randomly selected 139 ISFT patients to form a follow-up cohort. The model with the highest mean area under curve (AUC) of receiver operating characteristic (ROC) on both cohorts was identified as optimal model (OM). The follow-up cohort were stratified into high- and low-risk groups based on a fixed cutoff calculated by the OM. The OM (Stepglm[both] + GBM) in (Transformer + Clinic) models outperformed the OM (Lasso + GBM) in clinical models in distinguishing ISFTs from AMs on EVC, with an AUC of 0.936 (95

The basal ganglia play essential roles in motor control, emotion, learning and reward processing. Their dysfunction contributes to many neurological and psychiatric disorders. However, the gene regulatory programs defining basal ganglia cell-type identity and function remain poorly understood, limiting interpretation of disease-associated non-coding variants. Here, we present the first single-cell multiome atlas of histone modifications and transcriptomes across eight basal ganglia regions from neurotypical adult human donors. Joint profiling reveals cell-type-specific deployment of active and repressive cis-regulatory elements and gene regulatory networks, and suggests a combinatorial homeobox transcription factor code underlying cell identity. Integration with matched spatial transcriptomic MERFISH data uncovers regional heterogeneity of epigenomic landscapes. Comparative analysis between human and mouse medium spiny neurons uncovers conservation of core gene regulatory features. This atlas interprets non-coding risk variants of neuropsychiatric disorders and supports the development of a deep learning model to predict gene regulation and functional effects of disease-associated variants.

High-fidelity single-nucleotide-resolution mapping of abasic (AP) sites in mammalian genomes remains technically challenging due to low abundance and high background. Here we present DEPACE-seq (Dual-End PAB-Conjugated Endo IV-Cleaved Sequencing), a robust and easy-to-implement method for precise genome-wide profiling of AP sites. DEPACE-seq employs an N-pyrrolyl-alanine-2,2'-(ethylenedioxy)bis(ethylamine)-biotin (PAB) probe that selectively conjugates AP sites via a mild Pictet-Spengler reaction. The resulting PAB-AP adducts are efficiently and specifically cleaved by endonuclease IV, while remaining inert to other aldehyde-containing DNA bases. Independent library construction from both cleavage ends and the intersection of the resulting signals enable high-confidence identification of AP sites at single-nucleotide resolution. Application of DEPACE-seq across different cell types and damage conditions enabled high-confidence characterization of two AP-site populations: long-lived sites enriched in satellite and intergenic regions, and repair-intermediate sites induced by transient damage and enriched in transcriptionally active regions, both exhibiting cell-type-dependent features. Molecular dynamics simulations further elucidate how endonuclease IV accommodates bulky PAB adducts. Together, DEPACE-seq provides a robust platform for high-confidence, single-nucleotide-resolution mapping of AP sites in mammalian genomes, enabling systematic investigations of genome instability, DNA repair, aging, and cancer.

Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1) is a multifunctional protein central to DNA repair and redox regulation, yet its dynamic post-translational modifications (PTMs) remain poorly understood. Here, we report a biotin-regulated avidin-based nano-catcher (bMIPAPE1) capable of capturing active APE1 in living cells. By leveraging biotin-saturated avidin assembled onto magnetic nanoparticles and surface-imprinted with polydopamine, we engineered highly specific binding cavities for APE1 that enable retention of labile PTMs. This platform revealed 25 previously unreported PTMs across 18 residues of APE1, encompassing acetylation, phosphorylation, ubiquitination, methylation, S-nitrosylation, palmitoylation, and succinylation, and highlighting several PTM hotspots. Representative modifications include phosphorylation at Y264 and Y269, and acetylation at K63, with several PTMs associated with APE1 nuclear export. In addition to high specificity and intracellular compatibility, bMIPAPE1 attenuated both the DNA repair and redox-related functions of APE1. Our findings demonstrate the utility of artificial nanocomposites as tools for live-cell PTM profiling and functional modulation of target proteins, offering a powerful approach to decode protein regulation in living systems and identify potential therapeutic targets in cancer.

The role of 2-hydroxyglutarate (2HG) in the methylation process of O6-methylguanine-DNA methyltransferase (MGMT) promoter remains unclear. This study aimed to investigate the predictive efficacy and role of 2HG in MGMT promoter methylation. Patients who met the inclusion criteria were retrospectively included and divided into MGMT promoter methylation group (M) and MGMT promoter unmethylation group (UM). 2HG, Glutamate (Glu), N-acetylaspartate (NAA), Choline (Cho), 2HG/Creatine (Cr), 2HG/Glu and Cho/NAA were calculated. Intergroup differences were estimated using Mann-Whitney U test and Chi-square test. Subsequently, the receiver operating characteristic (ROC) curves were plotted for evaluating diagnostic efficacy of metabolic indices with statistical differences. Then, the causal steps approach was performed for discussing the mediation effect of 2HG. 75 patients (male: 52, female: 23, age: 46.81 ± 1.52 years) were included (48 in M, 27 in UM). Compared with UM, M exhibited higher 2HG, 2HG/Cr, 2HG/Glu, Cho/NAA and lower Glu, the differences were statistically significant (P < 0.05). 2HG/Glu exhibited the best diagnostic efficacy (area under curve: 0.788, [95

The study aimed to predict expression of pituitary transcription factor 1 (PIT1) in pituitary adenomas using habitat, intra-tumoral and peri-tumoral radiomics models. A total of 129 patients with pituitary adenoma (training set, n = 103; test set, n = 26) were retrospectively enrolled. A total of 12, 18, 14, 13, and 14 radiomics features were selected from the ROIintra, ROIintra+peri (ROIintra+2mm, ROIintra+4mm, ROIintra+6mm), and ROIhabitat, respectively. Then, three machine learning algorithms were employed to develop radiomic models, including logistic regression (LR), support vector machines (SVM), and multilayer perceptron (MLP). The performances of the intra-tumoral, combined intra-tumoral and peri-tumoral, and habitat models were evaluated. The peritumoral region (ROI2mm, ROI4mm, ROI6mm) of the combined model with the highest performance was individually selected for further peritumoral analysis. Moreover, a deep learning radiomics nomogram (DLRN) was constructed incorporating clinical characteristics and the peri-tumoral and habitat models for individual prediction. The combined modelintra+2mm based on ROIintra+2mm achieved a better performance (AUC, 0.800) than that of the intra-tumoral model alone (AUC, 0.731). And the habitat model showed a higher performance (AUC, 0.806) than that of the intra-tumoral model. In addition, the performance of the peri-tumoral model based on ROI2mm was 0.694 in the testing set. Furthermore, the DLRN achieved the highest performance of 0.900 in the test set. The DLRN showed the best performance for PIT1 expression in pituitary adenomas, followed by the habitat, combined modelintra+2mm, intra-tumoral model, and peri-tumoral model based on ROI2mm, respectively. These different models are helpful for the model choice in clinical work.

Spermatogenesis is a key process for the sexual reproduction species. In lepidopteran insects, spermatogenesis produces two different types of sperms, in which eupyrene sperm carry genomic DNA and fertilize eggs, whereas apyrene sperm are necessary for eupyrene sperm to enter eggs. However, functional genetic studies of spermatogenesis in Plutella xylostella remain a longstanding puzzle even though the phenomenon in lepidoptera has been widely documented more than a century. In this study, we particularly focus on the gene Nap1 which belongs to the Nucleosome assembly protein family. Our findings revealed that Nap1 was highly expressed in the testes, and the disruption of PxNap1 induced male sterility in P. xylostella, while the fertility of mutant females was comparable to wild-type females. Additionally, through immunofluorescence staining analysis, we found that the eupyrene sperm bundles presented diffusedly scattered nuclei in PxNap1 mutant males, while the nuclei in the wild-type were clustered together presented as needle shape. We also found that PxNap1 deficiency hinders the transfer of eupyrene sperm to the bursa copulatrix and spermatheca of females. However, the apyrene spermatogenesis was not affected in the PxNap1 mutant. RNA-seq analyses indicated that the defects of eupyrene sperm in PxNap1 mutants were related to energy metabolic such as pentose and glucuronate interconversions, biosynthesis of amino acids, and pentose phosphate pathway. Our study demonstrates that PxNap1 plays crucial function in eupyrene spermatogenesis and eupyrene sperm migration. Our research provides valuable insights for the genetic factors underlying reproductive processes in Lepidopteran insects.

Background:This retrospective study compared two types of gliomas and two subtypes of multiple gliomas. Methods:The clinical manifestations, magnetic resonance imaging (MRI) findings, pathological characteristics, and clinical outcomes of 188 patients with unifocal and 94 patients with multiple gliomas (59 with multifocal and 35 with multicentric gliomas) were analyzed. Results:Compared with patients with unifocal glioma, those with multiple gliomas were older (P=0.001) and more likely to be male (χ2 = 4.857, P=0.028). Patients with multiple gliomas had smaller extent of surgical resection (χ2 = 161.016, P<0.001) and a worse prognosis (χ2 = 43.733, P<0.001) than those with unifocal gliomas. Multiple gliomas were more likely to have a non-superficial location (χ2 = 51.758, P<0.001), obvious peritumoral oedema (χ2 = 9.688, P=0.008), intense enhancement (χ2 = 24.547, P<0.001), a higher WHO grade (P=0.001), a lower ratio of isocitrate dehydrogenase (IDH) mutation (χ2 = 51.770, P<0.001), and codeletion of 1p19q (χ2 = 8.637, P=0.003). Tumor location and IDH status were identified as independent risk factors for multiple gliomas (P<0.001 and P=0.003, respectively). Deep tumor location was found to be the only factor related to unfavorable overall survival (OS) in multiple gliomas. Patients with multifocal gliomas were more likely to be male than patients with multicentric gliomas (χ2 = 6.521, P=0.011). The locations of multifocal and multicentric gliomas were significantly different (P=0.048). WHO grade was identified as an independent prognostic factor (P=0.034) in patients with multicentric gliomas but not in those with multifocal gliomas. Conclusions:The demographic characteristics, extent of resection, radiological features, pathological features and prognostic factors differ between patients with multiple gliomas and those with unifocal gliomas. The clinical and radiological features differ between patients with different subtypes of multiple gliomas. Multiple gliomas located only in superficial regions are more likely to be multicentric gliomas and the prognosis is solely related to the WHO grades, providing valuable guidance for clinical treatment.

DNA methylation and hydroxymethylation are extensively reprogrammed during mammalian early embryogenesis, and studying their regulatory functions requires comprehensive DNA hydroxymethylation maps at base resolution. Here, we develop single-cell 5-hydroxymethylcytosine (5hmC) chemical-assisted C-to-T conversion-enabled sequencing (schmC-CATCH), a method leveraging selective 5hmC labeling for a quantitative, base-resolution, genome-wide landscape of the DNA hydroxymethylome in mouse gametes and preimplantation embryos spanning from the zygote to blastocyst stage. We revealed that, in addition to late zygotic stages, onset of ten-eleven translocation (TET)-mediated DNA hydroxymethylation initiates immediately after fertilization and is characterized by the distinct 5hmC patterns on the parental genomes shaped by TET3 demethylase. We identified persistent clusters of 5hmC hotspots throughout early embryonic stages, which are highly associated with young retroelements. 5hmC is also associated with different regulatory elements, indicating a potential regulatory function during early embryogenesis. Collectively, our work elucidates the dynamics of active DNA demethylation during mouse preimplantation development and provides a valuable resource for functional studies of epigenetic reprogramming in early embryos.

Tremor-dominant Parkinson’s disease (TD) and Essential Tremor (ET) are the two most common types of tremors, posing huge challenges in diagnosis. This study was to investigate the pathogenesis of tremors using brain morphology and employ artificial intelligence techniques for distinguishing them. The cortical thickness differences in TD were primarily centered on the right precuneus, while in ET were mainly observed in the right medial orbitofrontal cortex. Subcortical analysis revealed that TD patients primarily exhibited an increase in pallidum, whereas ET patients showed a significant reduction in thalamus. Causal network analysis indicated that in TD, the right temporal lobe exhibited the highest out-degree, and gradually extended to motor control regions. In contrast, ET primarily exhibits initial changes in the prefrontal and occipital visual cortices. Finally, by incorporating these specific characteristics, we developed a machine learning model capable of accurately distinguishing between different tremor types, providing valuable insights for clinical practice.

Desmoplastic infantile ganglioglioma (DIG) is a rare intracranial benign tumor occurring in infants under 2 years of age. It has good biological and behavioral characteristics and occasionally has malignant characteristics, such as multiple intracranial lesions, postoperative progression or recurrence, meningeal diffusion, and metastasis. We present a non-infant with DIG who underwent tumor progression. A 16-year-old girl presented with DIG in the cerebral cistern and underwent subtotal resection. A magnetic resonance imaging (MRI) of the brain 2 years later revealed that the area of abnormal enhancement in the surgical site was approximately the same as before, and follow-up was continued. A reexamination 5 years later showed that the residual extent of the operative area was significantly larger than before and involved the right frontal and temporal lobes, considering the progression of the residual part of the tumor. This case report focuses on the occurrence of DIG and its potential malignant features, as assessed through magnetic resonance imaging.

OBJECTIVE Craniopharyngiomas are rare, benign brain tumors that are primarily treated with surgery. Although the extended endoscopic endonasal approach (EEEA) has evolved as a more reliable surgical alternative and yields better visual outcomes than traditional craniotomy, postoperative visual deterioration remains one of the most common complications, and relevant risk factors are still poorly defined. Hence, identifying risk factors and developing a predictive model for postoperative visual deterioration is indeed necessary. However, there is still a lack of research on these topics. Therefore, the authors used the largest known case series of EEEA for craniopharyngioma to determine pertinent risk factors and develop a nomogram for the noninvasive preoperative prediction of visual outcome. METHODS A total of 483 cases of craniopharyngioma (338 in the training cohort, 145 in the validation cohort) between January 2019 and March 2023 were retrospectively reviewed, and related risk factors were identified. In total, 851 radiomic features from the MR images of each case were extracted. The least absolute shrinkage and selection operator algorithm was used to select features and construct the radiomic score (Rad-score). A support vector machine (SVM) classifier was adopted to construct a radiomic model. Moreover, a clinical-radiomic nomogram was built by multivariable logistic regression. The performance of the nomogram was assessed by its discrimination, calibration, and clinical utility. RESULTS The overall incidence of postoperative visual deterioration was 9.1%. A lack of intraoperative visual evoked potential (VEP) monitoring (OR 0.221, p = 0.001), larger maximum tumor diameter (OR 1.052, p = 0.014), and tight adherence (OR 2.963, p = 0.044) were demonstrated as independent risk factors for postoperative visual deterioration. The radiomic model using the SVM based on 8 selected features exhibited good discrimination in predicting adhesion strength in the training and validation cohorts (area under the receiver operating characteristic curve [AUC] 0.85 vs 0.80). Moreover, the nomogram incorporating the Rad-score and clinical factors showed AUCs of 0.827 and 0.808 in the training and validation sets, respectively, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSIONS Intraoperative VEP monitoring was proven to help reduce postoperative visual deterioration, while tight adherence and larger maximum tumor diameter were confirmed as independent risk factors. The radiomic model allowed a noninvasive prediction of the adherence strength between the optic nerves and craniopharyngioma. The nomogram showed a promising performance for noninvasively predicting postoperative visual deterioration and may serve as a useful tool for clinical decision-making and patient counseling.

The tremor-dominant (TD) subtype of Parkinson's disease (PD) is characterized by prominent tremor symptoms. However, the temporal and causal relationships between brain structural alterations in TD patients remain unexplored. A total of 61 TD patients and 61 matched healthy controls (HCs) were included in this study. The gray matter volume (GMV) of the bilateral precuneus (PCUN) was significantly reduced in TD patients. A structural covariance network analysis seeded with the left pallidum (PAL.L), which had the most significant differences, revealed a substantial reduction in covariance with precentral gyrus in TD patients. We performed a causal structural covariance network analysis using the TD duration as a pseudotime series. The PCUN, with the highest out-degree in the cortex, regulates numerous regions, including the supplementary motor area and the extensive temporal lobe. Machine learning was utilized to construct a model that accurately assesses the surgical prognosis based on the above cortical volume and clinical scale, with the aim of assisting in clinical deep brain stimulation (DBS) treatment. These findings suggested a progressive pattern of GMV changes extending from the PAL.L to the PCUN region and continuing to other brain regions, providing insights into the progression of TD and enhancing DBS treatment strategies.

Molecularly imprinted polymers (MIPs) have emerged as powerful artificial recognition platforms in the fields of separation science, chemical sensing, drug delivery, and biocatalysis, offering unparalleled tailor-made specificity and affinity for target molecules. Among various functional materials, dopamine-based MIPs have garnered exceptional attention in recent years due to their unique combination of advantageous physicochemical properties, including facile and controllable polymerization under mild conditions; rich interfacial interactions through diverse functional groups; excellent biocompatibility and biodegradability; and versatile secondary functionalization capabilities. This comprehensive review systematically summarizes and critically analyzes the latest advances in dopamine-based MIPs, with particular focus on innovative design strategies and their cutting-edge biomedical applications. Emphasis is also placed on the long-standing challenges of dopamine in molecular imprinting, and future perspectives on next-generation materials based on dopamine-based MIPs.