As the leading cause of mortality and long-term disability in China,cerebrovascular diseases present complex pathophysiological mechanisms involving neuroinflammation,immune dysregulation, and secondary brain injury.The seminal discovery of meningeal lymphatic system in 2015 has fundamentally transformed the understanding of central nervous system immune privilege. This system is now recognized as critical for cerebrospinal fluid drainage, metabolic waste clearance,and central nervous system immune surveillance. Recent advances in neuroimaging and molecular biology have elucidated the pivotal role of the meningeal lymphatic system in cerebrovascular disorders, particularly in modulating inflammatory responses, facilitating post-hemorrhagic erythrocyte clearance,and influencing overall disease progression and recovery. This review synthesizes the latest evidence on the functional contributions of the meningeal lymphatic system to cerebrovascular pathophysiology, to deepen the mechanistic understanding and to highlight its promising potential as a novel therapeutic target.

The gut microbiota coexists symbiotically with the host, playing critical roles in physiological processes such as nutrient metabolism, immune regulation, and intestinal barrier function. However, the microgravity environment in space can significantly alter the composition and function of the gut microbiota, posing numerous challenges to astronaut health. A thorough understanding of the impact of microgravity on the gut microbiota during spaceflight, along with investigating the underlying patterns and mechanisms, is crucial for developing effective health protection strategies. This article synthesizes previous research to systematically elucidate the effects of microgravity on the gut microbiota, including changes in community structure, metabolic dysfunction, and associated pathways. It focuses on the regulatory effects of exercise intervention on the gut microbiota in microgravity environments. As a non-pharmaceutical approach, exercise intervention alleviates microgravity-induced microbiota dysbiosis and metabolic disorders through mechanisms such as regulating the gut-brain axis, influencing inflammatory signaling pathways, and improving intestinal motility and blood supply. This article aims to summarize the impact and mechanisms of microgravity on the gut microbiota, especially the role of exercise in improving intestinal microecological homeostasis, thereby providing theoretical support for astronaut health protection.

Drug side effect prediction plays a crucial role in molecular structure optimization, dose adjustment, and the development of personalized medication strategies, representing an essential component of modern drug research pipelines and clinical medication management. Intelligent computational methods can effectively overcome the limitations inherent in traditional prediction approaches, such as high costs and prolonged development cycles. As an emerging deep learning paradigm capable of effectively modeling graph-structured data, graph neural networks (GNNs) can capture complex relationships between drug molecular structures and biological systems, thereby enhancing the accuracy and generalizability of side-effect prediction models. This article provides a comprehensive review of recent advances in GNN-based drug side effect prediction and discusses potential future research directions in this field.

Doxorubicin is a clinically used broad-spectrum antitumor chemotherapeutic agent that plays a key role in the treatment of various malignancies, including leukemia, breast cancer, and lymphoma. However, its clinical application is largely limited by dose-dependent cardiomyopathy , which can lead to heart failure in severe cases and significantly compromise the prognosis and quality of life of cancer patients. This article systematically reviews the core pathological mechanisms underlying doxorubicin-induced cardiomyopathy, including oxidative stress and lipid peroxidation, mitochondrial dysfunction,apoptosis and necrosis,autophagic dysregulation,energy metabolism reprogramming,inflammatory response network,ferroptosis and cuproptosis. It also summarizes targeted preventive and therapeutic strategies (such as targeted antioxidant therapy, mitochondrial protection, apoptosis inhibition, autophagic regulation). The purpose is to provide a systematic theoretical basis and research directions for the basic research and clinical prevention and treatment of doxorubicin-induced cardiomyopathy.

Glycolipid metabolic diseases are characterized by disorders of glucose and lipid metabolism, which involve multiple pathological mechanisms, including neuroendocrine dysregulation, insulin resistance, oxidative stress, inflammatory responses, and gut microbiota dysbiosis. Glycolipid metabolic disorders can lead to the occurrence and development of various diseases, such as type 2 diabetes, dyslipidemia, obesity, cardiovascular diseases, and metabolic-associated fatty liver disease. In recent years, as a newly identified acylation modification, lactylation modification has attracted considerable attention. It plays a crucial role in regulating protein function, and participates in the regulation of intracellular gene expression and a variety of signaling pathways. This article reviews the regulatory roles and research progress of lactylation modification in glycolipid metabolic diseases, explores its potential as a therapeutic target, with the aim of providing new insights into the prevention and treatment of glycolipid metabolic diseases.

Circadian clock genes,which are a group of genes that control and maintain the running of the circadian rhythms, exhibit rhythmic expression under constant light-dark cycles through a series of transcription-translation feedback loops, thereby maintaining normal physiological and biochemical homeostasis in the human body and participating in the onset and progression of diseases. Oral cancer is a malignant tumor originating from the oral mucosa, with an increasing incidence rate each year, closely associated with adverse lifestyle habits and environmental factors. Studies have shown that abnormal expression of circadian clock genes can affect the occurrence and development of oral cancer through various mechanisms. In this review, we summarize the mechanisms by which circadian clock genes affect the onset and progression of oral cancer, including their roles in the cell cycle, autophagy, immune microenvironment, and epigenetics, with the aim of providing a theoretical basis and new insights for the precise prevention and treatment of oral cancer.

Fibroblasts (FB) are widely distributed in the interstitial tissues of various organs and play a central role in skin wound healing.Due to their high plasticity,FB can respond to signals from the tissue damage microenvironment,undergoing phenotypic changes and dynamically maintaining tissue homeostasis and structural integrity.As a heterogeneous and functionally diverse cell type,FB not only regulate inflammation and angiogenesis,but also exhibit stem cell-like properties, playing a critical role in skin wound healing and pathological scar formation. Under physiological conditions, FB are moderately activated, synthesizing and remodeling extracellular matrix components, such as collagen, to promote tissue regeneration. Once healing is complete, they either undergo apoptosis or return to a quiescent state to maintain collagen turnover balance. However, during pathological scar formation, FB remain persistently activated and evade apoptosis, leading to abnormal collagen deposition and extracellular matrix components disorganization, ultimately resulting in functional impairment. This review primarily discusses the mechanisms by which FB contribute to skin wound healing and scar formation, aiming to clarify the biological behaviors of FB at different stages of wound healing. The goal is to provide new theoretical insights and potential therapeutic targets for clinical interventions in skin wound repair and the prevention of pathological scarring.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. In recent years, cuproptosis,a newly discovered form of programmed cell death,has gradually gained attention for its role in the pathogenesis of PD.The core mechanism of cuproptosis involves the binding of excessive copper ions to lipoylated proteins in the tricarboxylic acid (TCA) cycle,leading to abnormal protein aggregation and loss of iron-sulfur cluster proteins, thereby triggering mitochondrial proteotoxic stress.This article systematically reviews the impact of cuproptosis on key neuronal organelles-mitochondria,the endoplasmic reticulum ,and lysosomes and its molecular mechanisms.Cuproptosis exacerbates the damage and death of dopaminergic neurons by disrupting mitochondrial respiratory chain function, intensifying oxidative stress, inhibiting mitophagy, interfering with endoplasmic reticulum protein folding and calcium homeostasis, as well as impairing lysosomal acidification and the autophagy-lysosome pathway. Understanding the interactive network between cuproptosis and organelle dysfunction may provide new potential targets for PD treatment strategies.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor specifically expressed on the surface of microglia. It maintains the homeostasis of the neuroimmune microenvironment by regulating microglia proliferation, activation, and phagocytosis. Numerous studies have demonstrated that in Alzheimer's disease and Parkinson's disease, TREM2 primarily promotes M2-type microglial polarization via the DAP10/12 or PLCγ2 pathway, enhances microglial phagocytic function and alleviating oxidative stress and neuroinflammation. In epilepsy and stroke, TREM2 regulates the transformation of microglia into disease-associated microglia by activating the PI3K or Wnt pathway, thereby reducing neuroinflammation and facilating tissue repair. These findings suggest that TREM2 plays a crucial role in the pathological progress of the aforementioned neurodegenerative diseases; however, its underlying mechanisms and clinical significance remain inadequately characterized. Therefore, this review systematically and comprehensively summarizes the biological characteristics, pathophysiological functions, and potential mechanisms of TREM2, aiming to provide a reliable theoretical foundation for TREM2 and its associated signaling pathways as candidate targets for the clinical diagnosis and treatment of central nervous system diseases.

Intervertebral disc degeneration (IDD) is a common degenerative spinal disease in orthopedics, with its incidence increasing year by year. It is one of the main causes of low back pain. Due to the complex etiologies and pathological processes of IDD, its molecular mechanisms have not been fully elucidated, so there are currently no clear targeted therapeutic approaches. The Notch signaling pathway is a highly conserved signal transduction pathway. It is closely related to the progression of IDD by participating in regulating a series of biological processes such as extracellular matrix metabolism, inflammatory responses, cell homeostasis, and the microenvironment of intervertebral disc cells. By reviewing previous literature, the authors introduced the structure and transduction pathway of Notch signaling, then focused on elaborating the changes in Notch signaling expression and its impact on the pathological process of IDD. In addition, they summarized the current application status of the Notch signaling pathway as a therapeutic target for IDD, aiming to provide an important molecular biological basis for the pathogenesis of IDD and also expected to offer a theoretical basis for the development of therapeutic strategies targeting this pathway.

Ginsenoside Rh2 (G-Rh2), a rare saponin derived from the traditional medicinal herb Panax ginseng, is recognized as one of its most potent bioactive components. It exhibits diverse pharmacological properties, including anti-inflammatory, antibacterial, anti-allergic, cardioprotective, immunoregulatory, and neuroprotective effects, underscoring its considerable therapeutic potential. Preclinical studies have demonstrated that G-Rh2 exerts its anti-tumor activity through multiple mechanisms, such as inhibiting proliferation, inducing apoptosis, regulating autophagy, suppressing metastasis, modulating epigenetic and metabolic profiles, enhancing immunity, and reversing multidrug resistance. It also demonstrates efficacy in ameliorating adverse reactions induced by chemotherapy or radiotherapy. This review systematically summarizes the anti-tumor mechanisms of G-Rh2 across various cancer types and discusses relevant combination therapy strategies. We also outline recent advances in drug delivery systems designed to improve its pharmacokinetic profile and anti-tumor efficacy, aiming to provide new insights and potential targets for tumor treatment.

Rosacea is a chronic inflammatory skin disease primarily characterized by persistent facial erythema, telangiectasia, papules, and pustules. Its pathogenesis is closely associated with dysfunction of the gut-skin axis. Based on the gut-skin axis theory, this review systematically summarizes the relationship between gut dysbiosis and rosacea. Current evidence indicates that patients with rosacea exhibit characteristic alterations in gut microbiota composition, which contribute to the onset and progression of rosacea through multiple mechanisms, including the disruption of intestinal barrier integrity, induction of systemic immune dysregulation, and reduction of anti-inflammatory short-chain fatty acids (SCFAs).Furthermore,various therapeutic strategies targeting the gut-skin axis,such as probiotics/postbiotics,specific dietary interventions,and botanical extracts,have demonstrated potential efficacy in the management of rosacea.Future largescale prospective studies and multi-omics integrative analyses are warranted to establish causal relationships, thereby providing a theoretical foundation for the development of gut microbiometargeted personalized therapies for rosacea.

The striatum orchestrates the timing and vigor of movement through its direct and indirect pathways. The indirect pathway has been viewed as primarily suppressing motor output traditionally. However, recent studies indicate that dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) within the indirect pathway can either facilitate or inhibit behavior depending on context, thus exerting bidirectional control over movement. Accordingly, this review first synthesizes evidence on the diverse regulatory functions of D2-MSNs across multiple domains of motor control, including movement initiation, speed regulation, habit formation, and avoidance. It then examines the mechanisms by which D2-MSNs regulate movement at three levels: the characteristic patterns of receptor distribution on these neurons, their interactions with other striatal interneuron populations, and the organization of downstream neural circuits. Finally, the significance of D2-MSNs in various movement disorders is considered, in order to refine understanding of their role within basal ganglia models of motor control and to inform more precise therapeutic strategies for movement disorder-related conditions.