搜索结果：Science translational medicine

The gut microbiome supports digestion, immunity, and metabolism; its imbalance (dysbiosis) drives inflammation and metabolic dysfunction, contributing to chronic diseases such as diabetes, cardiovascular disease, inflammatory bowel disease, and autoimmune disorders. Medicinal plants provide a wide range of phytochemicals (such as polyphenols, flavonoids, alkaloids, saponins), which reach the colon and undergo two-sided interactions with microbes in the gut, acting as potential microbiome modulators and substrates of biotransformation into bioactive metabolites. This structured narrative review synthesises evidence from peer-reviewed studies indexed in PubMed, Scopus, and Web of Science over the last 10 years on the role of medicinal plants in microbiome-mediated chronic disease modulation. This literature is organised into three mechanistic axes: (i) perturbations, defined here as measurable shifts in microbial diversity or taxonomic composition relative to a baseline or healthy reference state, together with beneficial taxa enrichment; (ii) alterations in microbial metabolite output, especially short-chain fatty acids (SCFAs) and other immunometabolic mediators; and (iii) downstream host metabolic and immune signalling. Rather than broad descriptive summaries, the literature is organised using an axis-based mechanistic framework, highlighting key translational constraints such as botanical heterogeneity, dose/formulation variability, and inconsistent microbiome endpoint standardisation, that must be addressed to strengthen human evidence and clinical relevance. Illustrative microbiome-mediated processes involve botanicals such as turmeric (curcumin), ginseng (ginsenosides), and green tea (catechins), though evidence strength varies by study design. Future progress requires standardised phytochemical characterisation, microbiome-stratified trials, and integration of multi-omics with artificial intelligence analytics to enhance mechanistic insight, identify responders, and enable personalised plant-based microbiome therapies.

Generalist foundation models (GFMs) are renowned for their exceptional capability and flexibility in diverse tasks. In the field of medicine, while GFMs exhibit superior generalizability, specialist models excel in precision because of their domain-specific knowledge. Here we show a cooperative framework, Generalist-Specialist Collaboration (GSCo), that synergistically combines a powerful generalist model with lightweight specialists. In this framework, specialists provide expert guidance, such as diagnostic predictions and visually similar clinical cases, as contextual information to the generalist, which then makes a final diagnosis. We developed MedDr, an open-source GFM tailored for medicine, as well as a suite of lightweight specialist models crafted for specific downstream tasks. A comprehensive evaluation on 32 datasets across diverse medical modalities shows that MedDr outperforms state-of-the-art GFMs on downstream datasets. Furthermore, GSCo exceeds GFMs and specialists in medical image diagnosis and report generation. This approach offers an effective and computationally efficient paradigm for deploying GFMs in clinical settings, enhancing scalability and enabling precise analysis across a wide range of scenarios.

Emerging insights into the gut microbiome have sparked interest in exploring microbial therapeutics for treating inflammatory bowel diseases (IBD). However, no microbial therapeutics have yet shown clinical efficacy for IBD. E. coli Nissle 1917 (EcN) while effective for maintenance of remission, is only marginally effective for treating active colitis. We postulated that EcN effectiveness is hindered by the inflamed intestine, which prevents colonization since EcN lacks stress-resistance mechanisms necessary to persist during colitis. To address this, we introduced a fitness advantage, the ttr operon, to EcN (EcN::ttr), enabling tetrathionate, a byproduct of intestinal inflammation, to be used as fuel. We hypothesized that EcN::ttr bioengineered to bloom during colitis would effectively treat colitis. We evaluated the efficacy of EcN::ttr in murine colitis: acute DSS and a chronic mucin 2-deficient model. To determine the role of IL-10 in EcN::ttr protection, we tested its efficacy in IL-10-deficient mice. Finally, we co-incubated EcN::ttr with human colonoids to understand its effect on barrier proteins. EcN::ttr ameliorated colitis more effectively than EcN and 5-aminosalicylate. EcN::ttr bloomed during inflammation and promoted immunoregulatory responses reliant on IL-10 that limited leukocyte infiltration and decreased TNF-α+ myeloid resident cells. EcN::ttr induced functional changes in the gut microbiome related to mucosal healing, increased butyric acid, reduced bacterial translocation, and improved ZO-1 organization. We provide a proof-of concept study that bioengineering ttr into EcN unlocks a robust therapeutic effect during colitis. EcN::ttr may be a novel microbiome therapeutic for IBD due to its enhanced ability to successfully colonize the inflamed gut.

Accurate detection of KRAS codon mutations is essential for precision oncology in colorectal cancer (CRC), yet conventional liquid biopsy methods often lack sufficient sensitivity for rare ctDNA variants, particularly in early diseases. We developed a three-dimensional (3D) plasmonic KRAS microarray integrating blocked recombinase polymerase amplification with plasmon-enhanced fluorescence. Quencher-modified blocking probes suppress wild-type DNA while selectively enabling mutant signal amplification. A single primer-probe set per codon allows comprehensive detection of all substitutions within KRAS codons 12/13, 61, and 146. The platform achieved detection down to 1 fM by direct hybridization and 100 zM after blocked amplification, exceeding conventional PCR and next-generation sequencing sensitivity. Codon-level specificity was validated in CRC cell lines, with distinct signals for each mutation. Clinical analysis of 58 patients showed 100% concordance between tissue, plasma, and urine in mutation-positive malignant cases when sufficient input was available, indicating accurate reflection of tumor profiles. In benign tumors, detection was rare despite tissue mutations, likely due to limited ctDNA release.This plasmonic microarray enables ultra-sensitive, specific, and non-invasive detection, supporting early diagnosis, minimal residual disease monitoring, and longitudinal CRC management.

Brain aging is an inevitable but modifiable process in which cellular, molecular, and systemic alterations converge on the central nervous system to determine cognitive health span. Much of the existing literature examines the biological mechanisms of aging, the distinction between normal and pathological brain aging, and lifestyle or pharmacological interventions as separate domains, with few integrative analyses connecting these elements into a clinically relevant conceptual framework. This knowledge gap limits the effective translation of geroscience advances into practical, lifespan-oriented strategies for prevention and care. This review aims to: (1) distinguish systemic aging from cognitive frailty within a brain-oriented clinical framework; (2) summarize key molecular mechanisms of brain aging, including telomere shortening, genomic instability, epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction; (3) contrast clinical features of normal brain aging with neurodegenerative disease; and (4) evaluate emerging therapeutic strategies, including senolytics, gene modulation, and nutrient-sensing pathway regulation, while critically appraising the translational readiness of each. Integrating proactive lifestyle measures with advances in geroscience may provide a cohesive framework for promoting not only longer life but also healthier brain aging, although most interventional evidence to date remains preclinical, and substantial translational gaps must be addressed before these strategies can be validated in clinical practice.

Physical activity reduces the risk of mortality and age-related chronic diseases, yet its association with biological age measured by DNA methylation (DNAm) clocks remains unclear. This systematic review and meta-analysis aims to evaluate the association between physical activity and biological age measured by DNAm clocks. In this systematic review and meta-analysis, we conducted a systematic search of Embase, Cochrane Central Register of Controlled Trials, PubMed, Ovid, Scopus, and Web of Science from Jan 1, 2011, to June 6, 2025, to identify articles on the associations of physical activity and DNAm age, epigenetic age acceleration (EAA), or epigenetic age deviation in humans. Studies were included if they were peer-reviewed, published in English, included a study population with a mean or median age of 18 years or older, and investigated the association between DNAm clocks and physical activity in humans. Studies were excluded if the study population was a disease-specific population without controls. We evaluated risk of bias using an adapted Newcastle-Ottawa Scale and Cochrane Risk of Bias scale. We then performed a random-effects meta-analysis using reported or estimated standardised β coefficients and SEs. We also conducted a publication bias analysis and influence analysis. The study was registered with PROSPERO, CRD42024499021. We identified 34 437 articles and, after removal of duplicates and screening, 44 studies were included in the systematic review comprising 145 465 participants: 62 887 (43·2%) females and 82 578 (56·8%) males, with mean ages ranging from 24·1 years to 78·5 years. Across studies, higher levels of physical activity were generally associated with lower DNAm age, although many individual associations did not reach statistical significance. Seven cross-sectional studies contributed to the meta-analysis. Each one SD higher in metabolic equivalent of tasks-min per week was associated with 0·03 SD lower Horvath EAA (β=-0·03 [95% CI -0·05 to -0·01]) and 0·09 SD lower GrimAge EAA (-0·09 [-0·12 to -0·05]). No statistically significant association was observed for Hannum EAA or PhenoAge EAA. Higher physical activity is significantly associated with lower biological age as measured by Horvath EAA and GrimAge EAA. However, evidence is predominantly from cross-sectional studies, limiting causal inference. Future longitudinal studies and clinical trials using standardised, objectively measured physical activity are warranted to clarify dose-response relationships, and to determine whether physical activity can causally modify ageing trajectories, thereby informing precision strategies for healthy longevity. The National University of Singapore and the National Medical Research Council of Singapore.

Integration of Artificial Intelligence (AI), particularly deep learning, into medical imaging represents a profound shift in diagnostic medicine, moving from purely descriptive analysis to advanced predictive and prescriptive analytics. This Collection explores the rapid advancement of AI-driven tools in their specific fields such as oncology, cardiology, ophthalmology and so on, highlighting their potential to improve diagnostic accuracy, workflow efficiency, and personalized treatment planning. However, significant challenges remain, including the heterogeneity of medical image data, the "black box" nature of some intelligent models, and the critical hurdles of clinical integration and validation. The research presented here addresses these frontiers, showcasing innovations in algorithm development, explainable AI, and translational application. This Editorial synthesizes the contributions and outlines the essential collaborative pathway-uniting computer scientists, clinicians, and regulatory bodies-required to translate algorithmic promise into robust, trustworthy, and equitable clinical tools that genuinely improve patient care.

Angiogenesis is a fundamental prerequisite for functional tissue regeneration, and biomaterials that drive endogenous vascularization hold immense translational potential for treating tissue defects, organ damage, and ischemic diseases. Herein, gelatin methacryloyl (GelMA) and chitosan methacryloyl (CSMA) were synthesized via a copolymerization-based modification method. Hydrogel microspheres were prepared by emulsification, followed by cross-linking through photoinitiator-induced radical polymerization under UV light. Combined with freeze-drying, size-tunable porous GelMA/CSMA composite microspheres (G/CMS) were fabricated. The as-prepared G/CMS establish a favorable pro-regenerative microenvironment by integrating size-dependent mechanical feedback and charge-mediated cellular interactions. Specifically, CSMA incorporation imparted a positive surface charge, enhancing cellular affinity, while smaller diameters amplified mechanical stimuli promoting adhesion via mechanotransduction. In vitro, the optimized formulation (G/CMS-B) significantly promoted the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), and upregulated key angiogenic genes (VEGF, ANG, KDR) without exogenous growth factors. In vivo, subcutaneous implantation and hindlimb ischemia models confirmed accelerated neovascularization and blood flow recovery. The developed G/CMS exhibited excellent biocompatibility, controllable degradability, injectability, and excellent elastic recovery. This synergistic platform effectively modulates physicochemical cues to promote vascularization, offering a promising, cost-effective strategy for regenerative medicine.

There is a lack of data on the optimal gestational weight gain (GWG) in twin pregnancies in China. A multicenter retrospective study was conducted, containing 1247 twin pregnancies in both North and South China. Optimal GWG was defined as the interquartile range of GWG across pre-pregnancy body mass index stratum among low-risk women. The composite outcome was defined as any occurrence of preterm delivery, small for gestational age, large for gestational age, and hypertensive disorders during pregnancy. The study found that the optimal total gestational weight gain was 16-21.80 kg for underweight, 15.35-21.50 kg for normal weight, 12.10-20.25 kg for overweight, and 5.50-18.50 kg for obese subgroups. Corresponding gestational weight gain rates were 0.43-0.61 kg/week, 0.42-0.59 kg/week, 0.34-0.55 kg/week, and 0.15-0.51 kg/week. The proposed gestational weight gain ranges by our study were lower than the provisional Institute of Medicine (IOM) twin recommendation but higher than the Chinese Nutrition Society's singleton recommendation. Additionally, 46.11% of participants gained appropriate weight according to our suggestion, compared to 43.48% and 23.82% for the Institute of Medicine of twin guideline and the Chinese Nutrition Society's singleton recommendation, respectively. Furthermore, the association between the composite outcome with insufficient GWG defined by our suggestion was the strongest [adjusted odds ratio (95% confidence interval) = 1.74 (1.21-2.49)] among recommendations. Noteworthy, regional differences were observed. Southern Chinese women had a lower prevalence of adverse outcomes with proposed appropriate GWG ranges (80.78%) compared to the IOM twin guideline (82.04%). while northern women showed a slightly higher incidence of adverse outcomes under the proposed guidelines (65.67%) versus the IOM guideline (64.46%). Meanwhile, insufficient GWG was also more strongly linked to adverse outcomes in northern women (adjusted OR = 2.35) compared to southern women (adjusted OR = 1.15). These results indicating that northern women may need a higher optimal GWG threshold. Our study emphasizes the necessity of establishing official gestational weight gain guideline for Chinese twin pregnancies, and regional-specific guidelines may need to be considered.

To address clinical bottlenecks of traditional antipsychotic drugs, including delayed onset of action, significant peripheral side effects, and poor patient compliance, nanodelivery systems offer a feasible approach through their unique physicochemical properties to improve drug solubility, optimize in vivo transport, and enhance blood-brain barrier (BBB) penetration efficiency. This review focuses on the application potential and translational value of nanodelivery systems in psychiatric disorders. We systematically summarize recent advances in the construction strategies of mainstream nanocarriers, including lipid‑based, polymer‑based, inorganic nanomaterials, Metal-Organic Frameworks (MOFs), and Extracellular Vesicles (EVs), as well as commonly used nanoparticle preparation and characterization techniques. We briefly discuss key challenges facing nanoformulations, such as long‑term safety, large‑scale production, and batch‑to‑batch consistency, and highlight future directions driven by artificial intelligence and precision medicine. This review aims to provide insights for the rational design of nanodelivery systems for psychiatric disorders and to advance the development of precision psychiatry.

Neurological disorders are often devastating and notoriously difficult to repair, creating an urgent need for novel research models and therapeutic strategies. Neural organoids-three-dimensional, self-assembling structures derived from stem cells-have emerged as a powerful platform to address this challenge. Supported by enabling technologies like bioreactors and 3D printing, advanced maturation protocols have significantly enhanced their cellular diversity and functional utility. This progress has paved the way for their widespread application in developmental studies, disease modelling, and notably, regenerative medicine. Focusing specifically on the latter, this article reviews how neural organoid transplantation opens new avenues for treating CNS injuries and degeneration. We first elaborate on the development, characteristics, and maturation strategies of neural organoids. We then summarise the translational applications and achievements of transplanting both whole neural organoids and their derived vesicles, analyse the prevailing challenges in the field, and finally, outline future directions to advance the therapeutic potential of this technology.

Heart failure remains a leading global cause of morbidity and mortality, with limited capacity for myocardial regeneration following infarction. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a promising therapeutic resource due to their scalability, differentiation potential, and immunologic adaptability. Engineered cardiac patches, three-dimensional constructs of hiPSC-CMs combined with supporting cells and scaffolds, offer a strategy to deliver organized myocardium directly to injured hearts, overcoming the limitations of cell injection therapies. This review synthesizes evidence from 2010 to early 2025, spanning rodent, porcine, and non-human primate models, as well as the first clinical trials of hiPSC-CM patches. We highlight recent advances in maturation protocols, vascularization strategies, and scaffold engineering, while discussing two distinct translational paradigms: short-term paracrine support versus long-term remuscularization under sustained immunosuppression. Preclinical studies show that engineered patches improve graft survival, with engraftment rates ranging from 5 to 15%, alongside enhanced vascularization, electrical coupling, and left ventricular function. In large animal models, patches scaled to clinically relevant sizes achieved durable integration and improved hemodynamics. Of note, arrhythmogenic risk was lower than in intramyocardial injection models. Early human trials in Japan and Germany confirm feasibility and safety, with preliminary evidence of efficacy, including preliminary evidence of improved left ventricular ejection fraction and upgrades in NYHA functional class. Immunogenicity, graft maturation, and manufacturing scalability remain key hurdles, though innovations such as gene-edited hypoimmunogenic lines, multipronged maturation strategies, and bioreactor-based production offer potential solutions. Engineered hiPSC-CM cardiac patches represent a rapidly advancing frontier in regenerative cardiology. While early data indicate technical feasibility and measurable functional benefits, broader adoption will depend on resolving challenges of immune compatibility, arrhythmia prevention, and large-scale manufacturing. With coordinated progress in science, engineering, and regulation, cardiac patches may evolve into a transformative therapy for heart failure.

This review explores the role of in vitro electrical and mechanical stimulation in modulating wound-healing behavior, with a primary focus on the predominant skin cell types: fibroblasts and keratinocytes. By analyzing the existing literature, we delineate the complex relationships between stimulation parameters-such as voltage, current, frequency, and mechanical strain-and cellular responses, including proliferation and migration. Our data-driven approach compiled more than 390 experimental data points for electrical stimulation and over 170 for mechanical stimulation in vitro, constructing a comprehensive library of cell responses that were previously fragmented and difficult to compare across studies. We critically evaluate various stimulation platforms and configurations, emphasizing their influence on cellular mechanobiology and their translational potential in regenerative medicine. Ultimately, this review underscores the necessity of a multi-parameter optimization strategy to effectively exploit electromechanical cues for targeted skin tissue regeneration.

Stressors significantly impact human and animal health, increasing the risk of physical and mental disorders, in part by affecting the gut-brain axis. Although a link between stress, alterations in gut microbial composition, and the serum metabolite profile has already been established in humans, multiomics studies integrating the faecal microbiome and untargeted metabolomics remain unavailable. The objectives of the present study were twofold: first, to identify microbial and metabolic signatures associated with prolonged stress, and second, to evaluate the potential of integrative multiomics approaches to predict key metabolites and discover non-invasive faecal biomarkers of stress in pigs (n = 60). Gut microbial profiles were obtained by shotgun metagenomic sequencing, while faecal metabolites were analysed by untargeted reverse-phase liquid chromatography quadrupole time of flight mass spectrometry, followed by partial least squares discriminant analysis. Metabolite prediction from microbial features was performed using the machine learning method based on neural ordinary differential equations. Eleven discriminant metabolites were identified. In the control group, neurotransmitters such as serotonin and metabolites such as 2-acetamidophenol and sinapine (which possess anti-inflammatory and antioxidant properties) were the most prominent. Conversely, the stressed group exhibited elevated levels of xanthosine, pyrimidine bases (thymine and uracil), n-octadecylamine, and N-α-acetyl-L-lysine. N-octadecylamine (r = 0.37) showed a positive, and serotonin (r = -0.32) a negative correlation with hair cortisol. The results revealed interspecific interactions that modulated microbial and metabolic shifts between the control and stressed pig groups. Feature selection further identified 64 microbial genes that improved classification accuracy between control and stressed pigs to 91.06% and enhanced the prediction of key metabolites, including serotonin and xanthosine. Overall, this integrative multiomics framework elucidates complex microbiome-metabolite interactions and identifies non-invasive biomarkers of prolonged stress-induced metabolic dysregulation, providing valuable insights for animal welfare and translational human health research.

Beyond established risk factors such as genetics and hormones, the human microbiome has emerged as a pivotal player in breast cancer pathogenesis. This review delineates the technological evolution in breast microbiome research, spanning traditional culture methods to high-throughput sequencing and cutting-edge spatial omics. We elucidate the role of the gut-breast axis in modulating breast cancer development through its influence on estrogen metabolism, immune responses, and microbial metabolites. Furthermore, we analyze the distinctive compositional features of the intratumoral microbiota and their dual, context-dependent roles in promoting invasion, inducing immunosuppression, and driving metabolic reprogramming within the tumor microenvironment. Novel microbiome-based therapeutic strategies, including targeted microbiota depletion, engineered microbial therapeutics, and dietary interventions, are summarized. Finally, we discuss the translational potential of microbiome research in refining breast cancer risk prediction, evaluating treatment responses, and advancing personalized prevention and treatment strategies, ultimately contributing to improved patient outcomes.

While formalin-fixed paraffin-embedded (FFPE) samples are invaluable for human non-Hodgkin B-cell lymphoma translational research, effective methods for spatial profiling of chromatin accessibility and histone modifications in these tissues remain limited. Here, we introduce epi-Patho-DBiT, a platform that combines reverse crosslinking of FFPE tissues with spatially resolved assays for transposase-accessible chromatin using sequencing (spatial-FFPE-ATAC) or cleavage under targets and tagmentation (spatial-FFPE-CUT&Tag). Using spatial-FFPE-ATAC, we map epigenetic landscapes in mucosa-associated lymphoid tissue and follicular lymphoma, identifying chromatin variants linked to B-cell malignancy and resolving tumor karyotypes. Mitotic age inference reveals spatial tumor dynamics and uncovers cholesterol-mediated cell proliferation. Furthermore, spatial-FFPE-CUT&Tag elucidates genomic alterations during transformation of follicular lymphoma into diffuse large B-cell lymphoma and identifies DIP2C with dysregulated H3K4me3 and H3K27me3 levels. Unexpectedly, we observe elevated H3K27me3 occupancy at a chromosome 2 locus containing tumor-promoting genes, attributed to copy number amplification and thereby upregulation in transformed diffuse large B-cell lymphoma.

The incidence of renal cell carcinoma (RCC) and its associated economic burden have risen significantly in Taiwan. While targeted therapy has become a standard treatment, its real-world effectiveness and cost-effectiveness remain to be fully evaluated. This population-based cohort study utilized the Taiwan National Health Insurance Research Database and Cancer Registry to analyze 14,131 RCC cases diagnosed between 1998 and 2016. Key outcomes included life expectancy (LE), loss of LE, and lifetime medical costs. The cumulative incidence rate of RCC increased from 0.37 to 0.73% in men and from 0.23 to 0.36% in women. Significant LE loss was observed, particularly in patients under 50 years of age (14.38 years in men; 12.89 years in women). In advanced cases, targeted therapy yielded a slightly higher LE (4.43 years) compared to non-targeted therapy (3.63 years); however, the loss of LE was similar between groups. The real-world relationship between survival outcomes and lifetime medical costs of targeted therapy in Taiwan suggests suboptimal efficiency under current clinical practice. These findings suggest a need to re-evaluate reimbursement strategies by considering pharmacogenomic heterogeneity, implementing genomic profiling for precision medicine, and transitioning toward more effective combination therapy paradigms.

Defective clearance of apoptotic hepatocytes contributes to inflammation and progression of alcohol-associated liver disease (ALD), but the mechanisms regulating macrophage efferocytosis during alcohol exposure remain unclear. We investigated whether fatty acid synthase (FASN)-dependent lipid metabolism controls hepatic macrophage efferocytosis in ALD. Human liver tissues from patients with alcohol-related cirrhosis (AC) and controls (n = 18/group), together with experimental ALD mouse models (n = 6/group), were analyzed for hepatocyte apoptosis and hepatic macrophage alterations. Transcriptomic profiling (n = 3/group), pharmacological inhibition, and myeloid- or Kupffer cell-specific Fasn knockout mice (n = 6/group) were used to define the role and mechanism of FASN-mediated lipogenesis in macrophage efferocytosis. In patients with AC, hepatocyte apoptosis was markedly increased compared with controls (p < 0.0001), accompanied by increased accumulation of CD68-positive inflammatory macrophages (p < 0.001). In experimental ALD mice, hepatocyte apoptosis and monocyte-derived macrophage infiltration were also significantly increased (p < 0.0001). Mechanistically, ethanol impaired macrophage efferocytosis by more than 80% (p < 0.01). This was associated with inhibition of the PI3K/AKT/SREBP1 pathway, reduced FASN expression, and suppressed de novo lipogenesis. Reduced FASN expression decreased NRF2 activity and impaired TREM2 transcription, resulting in defective clearance of apoptotic cells. TREM2-positive hepatic macrophages were markedly reduced in both human AC and murine ALD (p < 0.0001). Consistently, Kupffer cell-specific Fasn deletion significantly aggravated hepatocyte apoptosis and liver injury in vivo (p < 0.01). Alcohol impairs macrophage efferocytosis by suppressing the PI3K/AKT/SREBP1-FASN-NRF2-TREM2 axis. Disruption of this lipogenic program promotes hepatocyte apoptosis and liver inflammation in ALD. Alcohol-associated liver disease is characterized by hepatocyte death and ongoing inflammation, but the mechanisms that connect these processes to macrophage efferocytosis remain poorly understood. Our research revealed that ethanol suppresses FASN-dependent de novo lipogenesis and downstream NRF2-TREM2 signaling in hepatic macrophages. Impairment of lipogenesis compromises efferocytosis, leading to an accumulation of apoptotic hepatocytes and increased monocyte infiltration. These findings underscore the potential of targeting macrophage lipid metabolism as a therapeutic strategy in ALD. However, further translational validation is needed before clinical application.

Meningeal lymphatic vessels (mLVs) have recently emerged as pivotal regulators of central nervous system homeostasis, orchestrating cerebrospinal fluid (CSF) drainage, metabolic waste clearance, and neuroimmune surveillance at the brain and meningeal interface. Stroke, ischemic or hemorrhagic, exerts profound functional insults on mLVs, disrupting clearance pathways. These disturbances not only exacerbate acute edema and neuroinflammation but also dictate long-term outcomes, including post-stroke cognitive decline. In this review, we synthesize current understanding of mLVs anatomy and physiology, emphasizing their dynamic remodeling after stroke. We further examine the context-dependent immune functions of mLVs, and their role in shaping post-stroke brain injury and repair. In addition, we discuss emerging therapeutic strategies targeting the glymphatic-lymphatic axis and outline key translational challenges. Although these findings support a framework in which impaired fluid clearance contributes to stroke pathophysiology, most mechanistic insights derive from preclinical models, and direct evidence in human stroke remains limited. Accordingly, therapeutic implications should be interpreted with caution and require rigorous clinical validation.