Yong Luo

Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, and a sustained neuroimmune response. Among immune-related targets, triggering receptor expressed on myeloid cells 2 (TREM2) is of particular interest because it is supported by human genetics, microglial biology, and expanding therapeutic development. TREM2 regulates microglial survival, phagocytosis, lipid handling, metabolic fitness, and plaque-associated responses, yet its therapeutic significance is more complex than a simple protective receptor model suggests. Although multiple TREM2-directed strategies have entered preclinical and early clinical development, recent evidence indicates that pharmacological target engagement does not necessarily translate into clinical benefit. We therefore propose that the therapeutic value of TREM2 is best understood through the concept of therapeutic window. TREM2 modulation is more likely to be beneficial when amyloid pathology is still being actively contained and microglial functional reserve remains preserved, whereas later disease stages, tau-associated neurodegeneration, receptor shedding, genetic heterogeneity, and pre-existing immune dysfunction may narrow or alter treatment benefit. Within this framework, soluble TREM2 (sTREM2) should be interpreted cautiously, as it may reflect receptor shedding, target engagement, microglial state, disease stage, or a combination of these processes rather than serving as a direct surrogate of efficacy. Viewed in this way, the central challenge of TREM2-directed therapy is to determine both when receptor modulation can still produce meaningful tissue protection and how the mode of receptor engagement shapes adaptive or maladaptive microglial programs.

Objective: This study aims to investigate the potential risks and molecular mechanisms by which exposure to polyethylene terephthalate microplastics (PET-MPs) induces ischemic stroke (IS) as a neurotoxic and vasculotoxic agent. Methods: We analyzed literature published between 2005 and 2025 on the association between IS and microplastics using bibliometric methods. IS-related expression profile data were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes and genes from WGCNA co-expression network modules were identified. PET-MPs-related targets were identified using public databases; after intersecting these with disease-related targets, GO and KEGG enrichment analyses were performed, and a PPI network was constructed. Three machine learning algorithms—LASSO, SVM, and Random Forest—were used to identify core genes, and their diagnostic value was evaluated using GSEA, immune infiltration analysis, ROC curves, and Bayesian networks. Finally, binding modes were validated through molecular docking and dynamics simulations. Results: Bibliometric analysis revealed that research has focused on the potential causal relationship between PET-MP exposure and IS. Thirty common targets between PET-MPs and IS were identified, with KEGG pathways showing significant enrichment in processes such as inflammatory response regulation, the NF-κB signaling pathway, the TNF signaling pathway, leukocyte transendothelial migration, and steroid hormone synthesis. Machine learning identified 8 core targets (PTGS2, BCL2A1, CA13, TOP2A, CYSLTR2, CES1, PLIN5, S1PR3), with an AUC of 0.988 for the ensemble model. Immune infiltration analysis using CIBERSORT revealed that the core genes are closely associated with macrophages and neutrophils; molecular docking and molecular dynamics simulations confirmed that PET-MPs adopt stable binding conformations with the 8 targets. Conclusion: PET-MPs may contribute to the development of IS by regulating neuroinflammation and immune imbalance through the aforementioned targets, providing new targets and a theoretical basis for understanding the mechanisms of their neurotoxicity and for the prevention and treatment of IS.

Nanomaterials have demonstrated substantial promise in the diagnosis and treatment of neurological and psychiatric disorders, offering novel strategies to overcome the limitations of traditional therapies. This review utilizes bibliometric analysis to evaluate global trends in nanomaterial research for neurological and psychiatric diseases, based on a corpus of 3,987 publications retrieved from the Web of Science Core Collection spanning from 1997 to August 2025. The analysis reveals a consistent upward trajectory in annual publications, reflecting substantial and growing international interest across diverse regions. Following an overview of global research dynamics, this review explores the pathogenesis of neurological and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, depression, and schizophrenia. The mechanisms underlying these conditions, including neuroinflammation, oxidative stress, protein aggregation, and neurotransmitter imbalances, are systematically discussed. Subsequently, the review focuses on how nanomaterials, including nanoparticles, nanocomposites, and nanocarriers, target these pathogenic mechanisms. The therapeutic applications of nanomaterials are evaluated with respect to their ability to modulate neuroinflammation, reduce oxidative stress, improve drug delivery to the brain, and facilitate the repair of neuronal damage. Despite the promising potential of nanomaterials, several challenges remain, including biocompatibility, targeted delivery, and scalability of treatment options. The review concludes by highlighting future directions for research, emphasizing the need for continued innovation in nanomaterial design and application to address these challenges and advance clinical treatments for neurological and psychiatric disorders.

Aims: Approximately 96% of the Gelao population lives in Guizhou Province, predominantly in Wuchuan and Daozhen counties. This study explored the prevalence of dementia and the factors associated with it among the Gelao ethnic group in this area. Methods: A stratified random cluster sampling method was used to conduct a face‐to‐face questionnaire survey with Gelao individuals aged ≥ 65 years from August to October 2022. The survey collected data on demographics, medical history, lifestyle, and dietary habits. Participants were assessed using the Chinese Mini‐Mental Status Examination (CMMS) and the Activities of Daily Living (ADL) scale. Dementia diagnoses were made according to DSM‐IV‐TR criteria. Results: Among the 2712 participants, the prevalence of dementia was found to be 24.74% (95% CI: 23.1–26.4). Multivariable analysis indicated that factors such as not residing in a nursing home, maintaining good tooth brushing habits, engaging in physical activity, visiting the market, playing mahjong, having a high income, drinking oil tea, and consuming Houttuynia cordata were associated with lower odds of dementia (all p < 0.05). Conclusion: The prevalence of dementia among older Gelao adults is notably high, especially among women. These results underscore the urgent need for targeted awareness campaigns, screening initiatives, and intervention strategies aimed at alleviating the dementia burden within this ethnic minority population.

Neuroinflammation is a key pathogenic factor for neurodegenerative diseases. Mesenchymal stem cell (MSC) transplantation, as a potential strategy for regul

Introduction: Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive memory decline, with neuropathological hallmarks including amyloid plaques and neurofibrillary tangles. Current treatments only alleviate symptoms and cannot halt disease progression. Icaritin (ICT), a natural compound, has shown neuroprotective potential. Transactive response DNA-binding protein 43 (TDP-43) is widely recognized as a key neuropathological hallmark of AD and related dementias. This study investigated the protective effects of ICT against TDP-43-induced damage in N2a/APP695swe (APP) cells and explored the underlying mechanisms. Methods: N2a/APP695swe/TARDBP cells overexpressing APP and TDP-43 were constructed via lentiviral transfection, and the optimal ICT dosage was determined using the CCK-8 assay. The effects of ICT on TDP-43 cell phenotypes were then assessed using CCK-8, ELISA, and Western blot. Finally, transmission electron microscopy, flow cytometry, assay kits, and Western blot were used to investigate the protective mechanisms of ICT. Results: ICT treatment significantly increased cell viability, reduced Aβ42 levels, and alleviated phospho-Tau and phospho-TDP-43 accumulation. Mechanistically, ICT improved mitochondrial morphology, decreased ROS levels, enhanced ATP production, and modulated the AMPK/mTOR and PINK1/Parkin autophagy signaling pathways to mitigate TDP-43-mediated cellular stress. Conclusion: ICT protects cells from TDP-43-induced mitochondrial dysfunction and autophagy impairment, providing mechanistic insight into its potential as a therapeutic agent for AD.

Neuroinflammation, particularly through the NLRP3 inflammasome, plays a significant role in the progression of Parkinson's disease (PD). Icaritin (ICT), a flavonoid compound derived from Epimedium, has demonstrated potential therapeutic effects on PD. In this study, an MPTP-induced PD mouse model was used to evaluate the impact of ICT. The mice were treated with ICT through intragastric administration, and their motor functions were assessed by the rotarod test and the pole test. Immunofluorescence was used to examine the expression of TH, Iba1, and GFAP, and Western blotting was used to measure changes in the levels of NLRP3 and other relevant proteins. The results showed that ICT significantly improved motor dysfunction induced by MPTP, reduced dopaminergic neuronal damage, diminished glial cell activation, and inhibited the expression of proteins in the NLRP3 signalling pathway. These findings suggest that ICT has a protective effect on the MPTP-induced PD mouse model and that its mechanism of action is likely related to the inhibition of NLRP3-mediated neuroinflammation. Graphical Abstract

Neuronal intranuclear inclusion disease (NIID) is a chronic progressive neurodegenerative disorder characterized by the formation of eosinophilic intranuclear inclusion bodies in the nuclei of neurons in the central, peripheral, and autonomic nervous systems, as well as visceral organs. The clinical presentation of this disease is diverse, manifesting as headaches, fever, altered consciousness, dementia, seizures, sensory and motor disturbances, and autonomic dysfunction, making it prone to misdiagnosis in clinical practice. This article reports a case of NIID diagnosed through skin biopsy and genetic testing, along with a review of relevant literature. It provides an overview of the characteristics and diagnosis of NIID, emphasizing the importance of early diagnosis and comprehensive treatment in managing this rare neurological disorder.