The central nervous system (CNS) maintains homeostasis and immune surveillance through a recently defined brain‐wide clearance network: the glymphatic–lymphatic axis. This system couples the intramural glymphatic pathway, responsible for convective fluid transport and parenchymal waste removal, with the meningeal lymphatic vessels (MLVs), which serve as the critical efferent route to the peripheral immune system. This review delineates the structural and functional foundations of each component, their regulatory dynamics, including the roles of sleep and aging, and their synergistic interplay in maintaining fluid balance, clearing metabolic waste, and facilitating neuroimmune communication. Mounting evidence identifies the dysfunction of this integrated axis as a common pathological mechanism across a spectrum of neurological disorders. We highlight its pivotal role in three key paradigms: acute injury (stroke), chronic proteinopathy (Alzheimer's disease, AD), and autoimmune dysregulation (multiple sclerosis, MS), where impaired clearance and maladaptive immune responses are central, recurring themes. The review critically evaluates emerging translational strategies aimed at therapeutically modulating this axis, including pharmacological targets (VEGF‐C, Piezo1 agonists), noninvasive neuromodulation (photo‐biomodulation, PBM), and surgical interventions (lymphaticovenous anastomosis, LVA). This synthesis positions the glymphatic–lymphatic axis as a fundamental physiological network and a pivotal target for novel interventions, outlining key future research directions in neurology.

Alveolar regeneration deficiency may lead to persistent emphysematous destruction in chronic obstructive pulmonary disease (COPD), lacking effective treatments to halt disease progression. Dysfunction of alveolar type II epithelial cells (AT2 cells), which serve as the progenitor in distal lung, is thought to be a major cause of alveolar regeneration deficiency. However, the mechanisms underlying AT2 cells dysfunction following injury and alveolar regeneration deficiency in COPD remain poorly understood. We aim to elucidate molecular mechanisms underlying impaired AT2 cells progenitor function, and better understand regeneration defects in COPD by integrating scRNA-seq analysis, chronic cigarette smoke-exposed murine model and alveolar organoid. Chronic cigarette smoke (CS)-exposed murine model was established to evaluate emphysematous destruction and AT2 cell function through immunostaining and organoid assays. Integrated analysis of patient and CS-exposed mice derived single-cell RNA sequencing data was performed to identify transcriptional alterations in AT2 cells. Focusing on the identified ITGA3, we performed functional validation and mechanistic investigation via genetic manipulation and pharmacological interventions in organoid as well as in vivo pharmacological interventions upon CS injury. Chronic CS exposure impaired AT2 cells proliferation and self-renewal capacity. Single-cell profiling revealed disrupted proliferation pathways and ITGA3 downregulation in AT2 cells. Mechanistically, ITGA3 regulates AT2 cells self-renewal function defects upon injury through FAK/YAP axis. And CS-induced reactive oxygen species (ROS) accumulation contributed to ITGA3 suppression and regenerative impairment. In vivo scavenging ROS with NAC restored CS-induced ITGA3 loss in AT2 cells, reactivated FAK/YAP signaling and ameliorated emphysematous pathology. Our study elucidates core regulatory role of ROS/ITGA3-FAK-YAP axis in AT2 cells renewal dysfunction in COPD by integrating single-cell genomics, preclinical models, and functional organoid studies, demonstrating ROS/ITGA3 as a new promising avenue for therapeutic intervention of COPD regeneration therapy.

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, is characterized by rapid recurrence and poor prognosis despite multimodal therapy.

Glioblastoma (GBM) remains difficult to control. Monoclonal antibodies (mAbs) have transformed the treatment of several extracranial cancers, but they have not consistently improved survival in GBM. This narrative review examines the main biological and translational barriers to antibody-based therapy. It also evaluates strategies to overcome them. We reviewed preclinical, translational, and clinical evidence on antibody delivery, target stability, the tumor microenvironment, target discovery, and emerging antibody formats. Heterogeneous blood–brain and blood–tumor barriers produce uneven intratumoral exposure, especially at infiltrative margins. Spatial and temporal heterogeneity promotes antigen loss and treatment escape. Lymphocyte dysfunction, myeloid dominance, and suppressive vascular and metabolic programs further limit immune activity. Receptor-mediated transcytosis and focused ultrasound may improve delivery. Single-cell and spatial profiling, surfaceome and endocytome proteomics, longitudinal sampling, and causal inference may improve target selection. Depending on their design, antibody–drug conjugates (ADCs) can deliver cytotoxic payloads, whereas bispecific constructs can enable immune redirection, dual-target recognition, or receptor-mediated transport. However, clinical benefit remains limited by construct design, target accessibility, regional exposure, toxicity, and inadequate biomarker selection. Successful translation requires modality-specific alignment of exposure at the relevant site of action, target requirements, immune dependence, molecular design, and safety. Biomarker-guided patient selection, spatial pharmacokinetic and pharmacodynamic validation, and early evidence of clinical benefit are also essential.

Neurological diseases, often caused by irreversible loss of terminally differentiated neurons, present considerable challenges to treatment due to the limited regenerative capacity of these neurons. Although induced pluripotent stem cells hold promise for neuronal regeneration, their clinical application is constrained by risks, including tumorigenicity, incomplete neuronal maturation, and immune rejection. Recent advancements in direct neuronal reprogramming, which bypasses the intermediate pluripotent stage by directly converting non-neuronal cells into functional neurons, offer a compelling alternative for in situ neuronal replacement in neurodegenerative diseases. Key transcription factors, such as NeuroD1, Ascl1, Sox2, as well as CRISPR activation (CRISPRa) of NGN2 and ISL1, have been explored to convert glial cells into neurons. However, several challenges remain. This review discusses the current applications of direct neuronal reprogramming technology in several neurological diseases. We further highlight the potential contamination issues in adeno-associated virus (AAV) delivery systems and propose a code of conduct to avoid artifacts and pitfalls. Finally, we point out future directions for expanding direct reprogramming targets, integrating organoid-based disease modeling, and advancing reprogramming regulation techniques.