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Cell-surface glycans play essential roles in cell communication, immune recognition, and disease progression. Their medical applications are supported by two important technological pillars: glycan recognition and glycan editing. This Review focuses on three key directions: recognition technologies, namely, in situ imaging and glycomic profiling, for detecting and profiling glycans; functional editing technologies, including genetic, enzymatic, chemical, and metabolic approaches, for precisely remodelling glycans; and medical applications driven by the synergy between recognition and editing, with a focus on four areas: biomarkers, lectin-based therapies, precision glycan editing, and cancer immunotherapy. Throughout the Review, five representative glycan classes-high-mannose N-glycans, mucin-type O-GalNAc, heparan sulfate, ganglioside GM3, and glycoRNAs-are used as recurring examples wherever possible. This Review offers an integrated perspective to navigate the process by which glycan recognition and editing technologies collectively drive the translation of cell-surface glycan research into clinical practice.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with significant attention focused on the development of therapeutic drugs and research into pathogenic mechanisms. In the real world, cardiotoxicity induced by multiple factors commonly exists and is closely associated with cardiovascular diseases. Traditional toxicity testing models (such as animal experiments and two-dimensional cell cultures) have limited clinical translation value due to species differences, inability to simulate the complex microenvironment of the human body, and cellular interactions. Cardiac organoids, as an emerging three-dimensional (3D) culture platform, possess 3D structure, multicellular composition, organ-specific functions, and self-organizing capabilities, which can highly mimic the physiological and pathological characteristics of the heart, providing a more precise humanized model for the study of cardiovascular disease mechanisms, drug development, and toxicity assessment. This paper systematically reviews the construction strategies of cardiac organoids and their application progress in toxicology: Firstly, it explores the construction standards and technical optimization of cardiac organoids, focusing on human-engineered heart tissue (hEHT) models and various cardiac organoid models that mimic the human heart, with particular attention to their unique characteristics, utility, and limitations. Secondly, through bibliometric analysis using CiteSpace, it reveals research hotspots and trends in cardiac organoid applications for toxicology, specifically by extracting collaboration networks, conducting co-citation analysis, and co-occurrence analysis. Finally, it summarizes specific applications of cardiac organoids in toxicology, including drug toxicity assessment, environmental pollutant toxicity evaluation, cardiac developmental toxicity studies, disease model construction, and multi-organ cascade studies for systemic toxicity assessment.

Despite the high prevalence of bone fractures in orthopedic practice, the mechanisms underlying muscle injury and regeneration remain poorly understood. Metal ions released from fracture fixation materials may improve patient outcomes by promoting muscle repair and preventing atrophy; however, the underlying mechanisms remain unclear. In this study, we investigated the role of magnesium ions (Mg2+) in regulating muscle regeneration in cardiotoxin-induced muscle injury. Mg2+ supplementation enhanced myogenic differentiation in C2C12 cells, as demonstrated by gain- and loss-of-function experiments targeting lysine-specific demethylase 6 A (KDM6A). Mechanistically, this effect was mediated by KDM6A-dependent demethylation of trimethylated lysine 27 on histone H3 (H3K27me3), rather than by KDM6B. Furthermore, Mg2+-treated myoblasts inhibited excessive osteoclast activation, partially reversing osteoclast-induced promotion of muscle atrophy. These findings reveal a KDM6A-dependent epigenetic mechanism by which Mg2+ coordinates muscle regeneration and modulates muscle-bone crosstalk. Collectively, this study provides a mechanistic basis for the therapeutic potential of magnesium-based biomaterials in mitigating disuse-induced muscle atrophy and improving outcomes following bone injury.

Polygenic risk scores (PRSs) quantify genetic susceptibilities, yet ancestry imbalance in genome-wide association studies (GWASs) limits the accuracy of monoracial PRSs in non-European populations. Here, we perform a multiancestry GWAS meta-analysis for lung cancer (76,953 cases and 1,886,372 controls), identifying 87 conditionally independent genome-wide significant loci, including two unreported cytobands. We use a PRS construction method, PRS-CSx, to develop a multiancestry PRS (PRSMA) which outperforms 32 published PRSs. To enhance predictive power, we construct a multitrait PRS (PRSMT) using CatBoost, integrating 32 cross-trait PRSs across three ancestries. Combining PRSMA and PRSMT, we generate PRSMAMT and validate it in independent cohorts (OncoArray, TRICL and All of Us). PRSMAMT demonstrates superior discriminability in European, Asian, and African populations, improves risk stratification, and identifies approximately 10% additional lung cancer cases in the UK Biobank. Individuals with elevated PLCOm2012 scores and high genetic risk exhibit a 12.64-fold higher cumulative risk than those with low scores and low genetic risk, supporting precision prevention strategies.

Bacterial-infected wounds present a critical clinical challenge due to persistent inflammation, impaired angiogenesis, and the lack of real-time treatment monitoring. To address these issues, we developed an innovative colloidal crystal hydrogel microneedle (CT MNs) patch based on CuS nanoparticles (CuS NPs) and tannic acid-berberine nanoparticles (TB NPs). This system integrates synergistic antibacterial/antioxidant therapy with structural color-based drug release self-reporting capability. Specifically, the CT MNs combine photothermal CuS NPs for near‑infrared (NIR)-triggered hyperthermia and temperature‑controlled drug release, the release of TB NPs for potent antibacterial/antioxidant activities, and the color changes of the inverse opal colloidal crystal for real‑time monitoring of drug release. In vitro assays demonstrated strong antibacterial effects (95.65% and 95.92% against E. coli and S. aureus, respectively) and outstanding ROS‑scavenging capacity (92.93% for DPPH and 97.36% for ABTS⁺). In infected rat models, the CT MNs + NIR group achieved rapid wound closure (94.41% by day 10), significantly outperforming the controls. This accelerated healing was attributed to the synergistic effects of photothermal ablation, TB NPs-mediated bacterial clearance, and ROS-scavenging-driven inflammation alleviation. Therefore, this work presents a theranostic dressing that merges targeted combination therapy with non‑invasive optical monitoring of drug release, offering a promising strategy for intelligent wound management.

Fibroblast growth factor receptor 3 (FGFR3) alterations and ERBB2 (HER2) amplification are clinically actionable genomic events in metastatic urothelial carcinoma (mUC). However, their prevalence and overlap in metastatic-specific cohorts remain incompletely defined. We evaluated their nationwide distribution and co-occurrence using the Japanese C-CAT registry. This retrospective study included patients with histologically confirmed mUC who underwent comprehensive genomic profiling with tissue-based FoundationOne assays between January 2019 and June 2025. FGFR3 positivity was defined as pathogenic mutations or fusions meeting companion diagnostic criteria, and HER2 positivity as ERBB2 amplification. Associations with clinicopathological variables were assessed using logistic regression. Co-occurrence was analyzed with Fisher's exact test. Among 1014 patients, FGFR3 alterations were identified in 157 (15.5%) and HER2 amplification in 150 (14.8%). Concurrent alterations occurred in 13 patients (1.3%). Under statistical independence, the expected co-occurrence rate was 2.3%; the observed frequency was significantly lower (P = 0.010; crude OR 0.47). In multivariable analysis, female sex (OR 0.58, 95% CI 0.36-0.93; P = 0.024) and upper tract origin (OR 0.57, 95% CI 0.39-0.84; P = 0.005) were independently associated with lower odds of HER2 amplification. HER2 amplification was independently associated with reduced odds of FGFR3 alterations (adjusted OR 0.49, 95% CI 0.27-0.88; P = 0.018). In this nationwide metastatic cohort, FGFR3 alterations and ERBB2 amplification were each detected in approximately 15% of cases and showed a significant but partial negative association. These findings clarify the molecular epidemiology of mUC and support comprehensive genomic profiling to guide biomarker-driven therapy.

Hematopoietic stem cell transplantation (HSCT) offers curative potential for hematologic malignancies and immune disorders, yet pulmonary complications remain major contributors to non-relapse morbidity and mortality. Traditionally attributed to immune suppression and graft-versus-host disease (GvHD), these complications are increasingly recognized to involve disruption of pulmonary microbial communities. A growing body of clinical and experimental evidence indicates that HSCT-associated perturbations in the lung microbiome, driven by conditioning, antimicrobials, immune injury, and infection, are associated with distinct post-transplant pulmonary phenotypes and, in some cohorts, with mortality risk. Whether these microbial shifts represent causal contributors to lung injury or contextual biomarkers of immune vulnerability remains unresolved, and this distinction carries direct implications for microbiome-targeted intervention. Dysbiotic shifts in the lung have been associated with both infectious and non-infectious complications, including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and fibrotic lung disease. Gut-lung microbial crosstalk may amplify or reflect systemic immune dysfunction, though the directionality of this relationship remains incompletely characterized. Multi-omics approaches, integrating metagenomics, metatranscriptomics, and metabolomics, are beginning to define the host-microbiome interaction signatures that distinguish injury subtypes and predict outcomes. This review synthesizes mechanistic insights into lung microbiome-immune interactions after HSCT, critically appraises the methodological constraints on the current evidence base, and evaluates microbiome-based interventions, including fecal microbiota transplantation, inhaled postbiotics, and precision antimicrobials, as candidate strategies for respiratory protection in transplant recipients, while acknowledging that prospective interventional evidence in this population remains limited.

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, with mortality disproportionately concentrated in low-and middle-income countries (LMICs), where screening infrastructure is limited. Although persistent high-risk human papillomavirus (hrHPV) infection drives nearly all cervical cancers through a prolonged preinvasive window, making the disease both preventable and detectable, current screening modalities face biological and operational limitations that constrain their global impact. Cytology-based methods suffer from moderate sensitivity and subjective interpretations. HPV DNA testing is highly sensitive, it lacks specificity for transforming infections and shifts the diagnostic burden toward triage and colposcopy. Meanwhile, visual inspection methods are accessible, they offer limited reproducibility. In this review, we adopt a target-centric diagnostic framework that organizes cervical cancer screening not by detection platform but by the biological class of the marker being interrogated. We first examined the molecular pathogenesis of cervical carcinogenesis, including HPV genotype-specific biology, viral integration dynamics, oncogene-driven transformation, and epigenetic consolidation, to establish the biological rationale for each biomarker category. We then systematically evaluated conventional screening modalities and their limitations before reviewing emerging diagnostic technologies across four target domains: HPV-derived markers (DNA, mRNA, capsid proteins), host cell-cycle regulators (p16INK4a, Ki-67), non-protein biomarkers (biothiols, volatile metabolites), and marker-free platforms (Raman/FT-IR spectroscopy, AI-assisted cytopathology). Particular emphasis is placed on point-of-care (POC) deployability, noninvasive sampling strategies, and the integration of multilayered risk stratification into scalable screening pathways. By mapping diagnostic innovation onto the biological continuum of cervical carcinogenesis, this review provides a conceptual foundation for developing next-generation screening approaches that align molecular precision with global accessibility, thereby supporting progress toward the World Health Organization goal of cervical cancer elimination.

Neutrophil extracellular traps (NETs) have emerged as dynamic extracellular platforms that integrate innate immunity, adaptive immune activation, and immunothromboinflammation. Rather than representing a single cell-death pathway, NET formation constitutes a context-dependent continuum shaped by the coordinated activation of multiple mechanisms, including NADPH oxidase-derived reactive oxygen species, calcium signaling, mitochondrial reactive oxygen species, PAD4-mediated chromatin remodeling, and metabolic reprogramming. The mechanistic architecture and pathogenic consequences of NET formation vary substantially across inflammatory rheumatic diseases. In gouty arthritis, NETs may amplify NLRP3 inflammasome activation and exacerbate acute inflammation, whereas aggregated NETs can contribute to inflammatory resolution during remission. In rheumatoid arthritis, NETs are enriched in citrullinated autoantigens, thereby promoting anti-citrullinated protein antibody production and contributing to joint structural damage. In systemic lupus erythematosus, NETs containing oxidized mitochondrial DNA enhance nucleic acid sensing and type I interferon responses, while defective NET clearance further aggravates immune dysregulation and organ injury. We propose that NET imbalance in inflammatory rheumatic diseases should not be interpreted as a uniform NETosis process, but rather examined through a disease-specific, four-dimensional framework encompassing mechanisms of formation, molecular composition, clearance capacity, and immunological consequences. Therapeutic strategies targeting NETs are accordingly evolving from broad suppression of NET formation toward multilayered approaches that combine modulation of NET generation with restoration of NET clearance. Nevertheless, clinical translation remains constrained by infection risk, disruption of thromboinflammatory homeostasis, and insufficient patient stratification. Overall, NET imbalance is more likely to function as a disease-specific amplifier of inflammation than as a universal initiating factor. Future studies should establish disease-resolved molecular atlases of NETs and advance biomarker-guided precision intervention strategies.

Artificial intelligence (AI) is transforming drug discovery and development, fields historically constrained by long timelines, high costs, and substantial attrition. Recent advances, particularly in generative modeling, enable an accelerated and increasingly systematic exploration of vast chemical and biological spaces, improving molecular interaction modeling and streamlining the identification and optimization of therapeutic candidates. However, the true utility of this expanded search space remains strictly bounded by the quality of upstream data and the logistical constraints of downstream experimental validation. Emerging platforms, including scaffold-aware and 3D molecular design tools (e.g., AlphaFold, MoleR, and PocketCrafter), single-cell foundation models, and large language models (LLMs), are expanding AI's applicability across the research and development pipeline, spanning target identification, drug discovery, lead optimization, phenotypic screening, and precision biology.AI is also increasingly integrated into preclinical and clinical research workflows, informing adaptive trial design, enabling AI-driven drug repurposing, and supporting the development of safer and more personalized therapies. While the U.S. FDA has approved numerous AI-enabled medical devices and software tools, no fully AI-discovered and AI-designed drug has yet received marketing approval. Nonetheless, several AI-originated candidates have progressed into clinical development, underscoring AI's growing translational impact. Collectively, these advances position AI as a collaborative "lab partner," capable of uncovering non-intuitive molecular designs, accelerating target and lead optimization, and enabling exploration of previously inaccessible chemical and biological space to inform downstream development and clinical decision-making. Despite gains in efficiency, scalability, and cost reduction, the broader impact of AI depends on access to high-quality multimodal data, robust regulatory and ethical frameworks, and careful recognition of methodological limitations. This review critically examines the evolution of AI approaches, highlighting key challenges and opportunities that shape the future of data-driven therapeutic innovation.

Dose-dense (DD) adjuvant chemotherapy represents a standard treatment for patients with high-risk node-positive early-stage HER2-negative breast cancer (BC). In this exploratory analysis of the GIM2 trial, we investigated the efficacy of DD chemotherapy among patients with HER2-negative BC according to HER2 immunohistochemistry (IHC) score. Patients with node-positive early BC were randomized to receive either DD or standard schedule anthracycline- and taxane-based chemotherapy. HER2 status was assessed locally. Tumours with HER2 score 0 were classified as HER2-zero, those with a HER2 score 1+ or 2+ without ISH amplification as HER2-low. Tumours classified as HER2-negative with unknown IHC score were considered as a separate subgroup. Overall, 1243 subjects were eligible for this analysis, with 475 (38.2%) tumours classified as HER2-zero, 446 (35.9%) as HER2-low and 322 (25.9%) as HER2-negative with unknown IHC score. At a median follow-up of 14.9 years (IQR 8.4-16.2), no interaction was observed between treatment effect and HER2 status in invasive disease-free survival (iDFS) (p for interaction = 0.42) nor in overall survival (OS) (p for interaction = 0.34). Efficacy of DD chemotherapy was observed regardless of HER2 status: among patients with HER2-zero tumours, adjusted hazard ratio (aHR) for iDFS was 0.62 (95% confidence interval [CI] 0.45-0.85) and for OS was 0.55 (95% CI 0.36-0.84). Among patients with HER2-low tumours, aHR was 0.82 (95% CI 0.61-1.11) for iDFS and 0.84 (95% CI 0.57-1.23) for OS. In patients with HER2-negative high-risk early BC, the benefit of DD chemotherapy was observed irrespective of HER2 status. (NCT00433420).

Inotuzumab ozogamicin, an anti-CD22 antibody-drug conjugate, has demonstrated high response rates and measurable residual disease (MRD)-negativity in acute lymphoblastic leukemia (ALL). This phase 2 single-center study evaluated inotuzumab 0.6 mg/m2 day 1 and 0.3 mg/m2 day 8 (cycle 1) followed by 0.3 mg/m2 days 1 and 8 (cycles 2-6) for adults with B-cell ALL in morphologic remission with detectable MRD (≥1 × 10-4 by multiparameter flow cytometry, BCR::ABL1 transcripts ≥0.01% by polymerase chain reaction [PCR], or ≥1 × 10-6 by next-generation sequencing [NGS]). Thirty-seven patients (median age 49 years) were treated, including 17 with Philadelphia-chromosome (Ph)-negative ALL and 20 with Ph-positive ALL. Twenty-eight patients (76%) were in first remission (CR1). Overall, 26 patients (70%) achieved MRD-negativity, including 76% of patients with Ph-negative ALL and 65% of patients with Ph-positive ALL. The NGS MRD-negativity rate was 73%. With a median follow-up of 50 months, the median overall survival (OS) was 61 months, with a median relapse-free survival (RFS) of 40 months. Patients treated in CR1 vs CR2+ had a median OS that was not reached versus 14 months, respectively (p = 0.056). Three cases (8%) of non-fatal sinusoidal obstructive syndrome (SOS) were observed. Inotuzumab was safe and effective at eradicating MRD.

Immunodeficiency can precede and directly contribute to cancer development, particularly in B-cell lymphoproliferative disorders (B-CLPDs), where immune dysfunction is often intrinsic to the disease. A subset of such patients initially classified as having secondary immunodeficiency (SID) resulting from the BCLP may harbour underlying primary immunodeficiencies (PIDs). Recognizing the pattern of these hidden PID patients not only refines disease classification but also expands our understanding of the genetic determinants of cancer-associated immunodeficiency. Identification of tumour somatic variants that overlap with germline genes causative of PID uncovers novel mechanisms of immune dysfunction in B-CLPD, thereby providing new avenues for precision oncohaematology. This evolving host-centred perspective supports individualized, anticipatory care; enhances early detection of immune-mediated complications enabling tailored treatment responses; provides informed family counselling; and improves long-term outcomes for patients.

Within the central nervous system (CNS), motor neurons constitute the principal and highly specialized functional units responsible for the precise regulation of somatic motor activity. Their developmental processes and plasticity mechanisms directly underpin the establishment and maintenance of neural circuits. This review offers a focused overview of the developmental processes and functional characteristics of motor neurons, while clarifying the definition of motor neuron plasticity. It further elucidates the intricate interplay between plastic alterations and the onset of injury, whereby aberrant plasticity acts as both a critical determinant in motor neuron injury and an accelerator of motor function deterioration. Building on these insights, the review constructs a multidimensional classification framework of motor neuron injury and further elaborates on the core molecular mechanisms of motor neuron regeneration, including signaling pathway regulation, epigenetic modifications, and maintenance of microenvironmental homeostasis. Conclusively, it summarizes the existing therapeutic strategies for motor neuron injury-related disorders, such as targeted gene therapy, cell replacement therapy, and neuromodulation technology, while dissecting the intervention mechanisms and limitations of each strategy. Although extensive studies have separately investigated various aspects of motor neurons, this review establishes a comprehensive framework that integrates findings from developmental mechanisms to therapeutic strategies and provides a comprehensive theoretical reference for future research on precision therapeutics, and facilitates bridging preclinical research and clinical translation.

PD-L1 tumor proportion score (TPS) is used to guide immunotherapy in non-small cell lung cancer (NSCLC), yet its ability to predict pathological response in the neoadjuvant setting remains limited. Thirty pathologists from 11 countries independently assessed PD-L1 TPS in pre-treatment biopsies and residual viable tumor (RVT) in matched resection specimens after neoadjuvant chemoimmunotherapy in 30 digitized cases from the ReGraDE (regression grading in Germany) study. Interobserver agreement was evaluated using intraclass correlation coefficients (ICC) and Fleiss' kappa. Associations between TPS and RVT were analyzed using Pearson correlation, and correlations derived from single-rater and averaged TPS were compared using the Williams test. Interobserver agreement was moderate for both TPS and RVT (ICC = 0.74, 95% CI 0.60-0.87, and ICC = 0.74, 95% CI 0.62-0.85, respectively) and became near-perfect when mean scores per case were calculated across observers (ICC = 0.99, for both). However, TPS remained poorly correlated with RVT for both single-rater assessment (r = -0.17, p = 0.38) and averaged TPS (r = -0.16, p = 0.39) with no significant difference between these approaches (p = 0.96). Differences in interpretation thresholds were observed particularly in borderline cases around the 1% TPS cut-off and in distinguishing 0% from minimal RVT, but did not account for the lack of association between TPS and RVT. Systematic differences were observed depending on individual professional experience, particularly in borderline cases. Interobserver variability does not explain the limited predictive value of PD-L1 TPS in the neoadjuvant setting, suggesting an intrinsic limitation of the biomarker.

Research misconduct poses a serious threat to academic integrity, particularly in medical sciences. This study aimed to estimate the prevalence of various forms of research misconduct include plagiarism, data fabrication or falsification, authorship misconduct, salami slicing, and purchasing research work among postgraduate students in Iranian medical universities using the Unmatched Count Technique (UCT). A cross-sectional survey was conducted among postgraduate students from multiple Iranian medical universities using a double-list version of the unmatched count technique (UCT). The questionnaire was administered in two sequential waves, with approximately half of participants completing List A and the remaining participants completing List B, ensuring that each respondent received only one list version. For each research misconduct behavior, prevalence was estimated by calculating the mean difference in endorsement counts between lists containing the sensitive item and corresponding control lists with only non-sensitive items. In the double-list design, prevalence estimates were computed separately for List A and List B, with sensitive items counterbalanced across list positions to control for order effects. The final prevalence was calculated as the average of the two list-specific estimates, improving precision and reducing list-order bias. The most commonly reported misconduct was using others' ideas or phrases without proper citation (43%), followed by dishonest result reporting (38%), data fabrication or deletion (34%), and authorship misrepresentation (34%). Salami slicing was reported by 26%, and 20% admitted to purchasing parts or all of a research project. The UCT survey tool demonstrated acceptable reliability, with intraclass correlation coefficients (ICCs) ranging from 0.64 to 0.84. The findings indicate a troubling level of research misconduct among postgraduatestudents in Iran's medical sciences universities. This highlights the need for effective ethics training, stronger academic integrity policies, and enforceable institutional mechanisms to promote responsible research conduct and protect the future credibility of medical professionals.

Colorectal cancer is one of the most prevalent malignant tumors worldwide. Early screening relies on accurate polyp detection during colonoscopy. Polyps in colonoscopic images exhibit diverse morphologies, indistinct boundaries, and low contrast. Specular reflections, fold occlusions, and imaging artifacts further complicate detection, which fail to meet the requirements of real-time clinical assistance. To address these challenges, we propose BCP-YOLO (You Only Look Once), a high-precision, relatively lightweight polyp detection framework built upon an improved YOLOv8 architecture, designed to achieve a well-balanced trade-off between detection accuracy and computational efficiency. First, to mitigate complex background interference and improve small polyp detection, a BiFormer module is integrated into the backbone network to enhance focus on salient polyp regions while suppressing noise. To alleviate boundary ambiguity, the CARAFE content-aware upsampling operator is incorporated into the feature fusion stage, to refine lesion boundaries and spatial details. PConv module is employed to optimize network efficiency, reducing computational cost while maintaining detection performance. Experimental results on the Kvasir-SEG and CVC-ClinicDB datasets demonstrate that BCP-YOLO achieves a mean average precision (mAP0.5) of 88.5% on Kvasir-SEG, representing a 3.4% improvement over the YOLOv8 baseline. Precision and recall increase by 5.5% and 1.3%, respectively. The model contains 11.7 M parameters and achieves an inference speed of 104.1 frames per second (FPS). Five-fold cross-validation on both datasets validates its strong generalization capability and robustness. The method provides a high-accuracy and deployable solution for computer-aided diagnosis in real-time colonoscopy, offering significant potential to improve the reliability and efficiency of early colorectal cancer screening.

Prenatal exposure to air pollutants has been linked to developmental delays in early childhood. This study investigated the association between prenatal exposure to ambient manganese (Mn) and delays in achieving specific neurodevelopmental milestones. Data were obtained from a nationwide population-based cohort study that recruited children born in 2005 and their mothers. Developmental outcomes were assessed by conducting home interviews at 6 and 18 months of age. Gestational exposure to ambient Mn was estimated using a land-use regression model enhanced with machine learning. Associations between Mn exposure and delayed milestone attainment were evaluated using multivariable logistic regression, adjusting for child, maternal, household factors, and co-exposure to particulate matter and nitrogen dioxide. A total of 17,683 term singleton births without congenital anomalies were included. Mn exposure during mid-gestation showed more consistent associations with later attainment of selected developmental milestones. After adjustment for relevant covariates, each 1 ng/m³ increase in second-trimester Mn exposure was associated with higher odds of delayed gross motor, fine motor, language, and social milestones ("walking with support": adjusted odds ratio [aOR] = 1.028; 95% confidence interval [CI]: 1.004-1.053), fine motor skills ("drawing arbitrarily": aOR = 1.081; 95% CI: 1.053-1.109), language milestones ("waving goodbye": aOR = 1.048; 95% CI: 1.022-1.075; "calling a parent meaningfully": aOR = 1.050; 95% CI: 1.021-1.080), and social interaction ("drinking with both hands": aOR = 1.045; 95% CI: 1.021-1.071). These findings suggest modest associations between prenatal ambient Mn exposure, particularly during mid-gestation, and early neurodevelopmental timing.

Chronic liver disease represents a major global public health challenge, and its malignant progression to hepatocellular carcinoma is the leading cause of death among affected patients. Gut microbiota dysbiosis is a critical driver of this process. As the central hub of the "gut-liver axis," the gut microbiota, when disrupted, compromises the integrity of the intestinal mucosal barrier, promoting the translocation of microbial metabolites, such as lipopolysaccharides and aberrant secondary bile acids, to the liver. In turn, key signaling pathways become activated, including TLR4/NF-κB, Wnt/β-catenin, and PI3K/Akt, sustaining persistent hepatic inflammation and oxidative stress. These pathological processes accelerate the progression from liver fibrosis to cirrhosis, promote genomic instability, and suppress tumor suppressor gene expression, paving the way for the malignant transformation of hepatocytes. Leveraging its holistic regulatory properties, characterized by multi-component, multi-target, and multi-pathway actions, Chinese medicine can intervene at multiple stages of this inflammation-to-cancer cascade by modulating both the structure and function of the gut microbiota. It does so first by enriching beneficial short-chain fatty acid-producing bacteria, such as Lactobacillus and members of the phylum Firmicutes, which helps restore the intestinal mucosal barrier, limit endotoxin translocation, and alleviate hepatic inflammation and fibrosis. In parallel, by normalizing bile acid metabolism and reestablishing gut microbial homeostasis, Chinese medicine counteracts the development of a tumor-permissive microenvironment marked by immune suppression and DNA damage in hepatocytes induced by microbial metabolites. At the same time, it enhances anti-tumor immune responses mediated by CD8+ T cells and other immune effectors. Drawing on evidence from multi-omics analyses and clinical studies, this review examines the core mechanisms and recent advances regarding how Chinese medicine monomers and formulations modulate the gut microbiota to impede the progression of chronic liver disease to HCC. It highlights gut microbiota dysbiosis as a key driver of hepatocarcinogenesis and highlights the therapeutic potential of targeted microbiota regulation by Chinese medicine, providing a conceptual foundation and strategic approaches for the precision prevention and treatment of hepatocellular carcinoma.