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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by deterioration in memory, cognition, and learning ability. Its etiology is complex and influenced by multiple factors, including genetics and environment. With advancing research into mitochondrial function and mechanisms, impaired mitophagy has been proposed as a significant mechanism contributing to AD. The ApoE ε4 allele, a high-risk genetic factor for AD, may play a key role in disease pathogenesis by inducing mitophagy dysfunction and apoptosis. From the perspective of APOE gene polymorphisms, this study investigates abnormal changes in mitochondrial function and autophagy in humanized APOE4 mice primary astrocytes under oxidative stress, as well as the regulatory effect of curcumin (Cur) on mitophagy and oxidative stress-induced apoptosis, thereby exploring its potential to ameliorate AD through targeting mitophagy. Mitochondrial function analysis revealed that APOE4 expression reduced the antioxidant capacity and respiratory function of primary astrocytes, leading to mitochondrial membrane damage, intracellular reactive oxygen species (ROS) accumulation, and decreased ATP production. Curcumin effectively protected mitochondrial integrity, reduced the number of damaged mitochondria, improved overall mitochondrial function, and helped maintain mitochondrial homeostasis involving in PINK1/Parkin pathway. Regarding autophagy and apoptosis, curcumin was shown to restore autophagic flux, mitigate autophagy disruption caused by oxidative stress, and reverse early-stage apoptosis. Show less

Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E ( Community-residing, Spanish-preferring Mexican/Mexican American adults ( Participants recognized AD as a memory disorder influenced by aging and genes but were largely unfamiliar with AD genetic testing. Testing was viewed as useful for diagnosis rather than future risk prediction, with limited perceived value for cognitively normal individuals without a family history. Despite this limited familiarity, participants expressed interest in AD research involving genetic testing. Findings suggested a perceived responsibility to use AD genetic testing despite limited awareness of its purposes, applications, and clinical implications. Participants' responses reflected a present-oriented health disposition: Genetic testing was viewed as appropriate once symptoms emerge rather than as a proactive tool for anticipating future decline, consistent with current clinical practice outside autosomal dominant AD. Educational materials co-created by community members and researchers may address these gaps by explaining both limitations of genetic testing in isolation and its potential future applications, including how genetic and multimodal biomarker data may inform risk estimation and prevention-focused decision-making. This approach may foster a future-oriented health disposition while remaining responsive to social and structural contexts. Future work is needed among other H/L heritage groups with differing social and structural experiences, migration histories, and language primacy. Show less

Depression, a global mental disorder, is linked to gut-brain axis (GBA) dysfunction. This review explores how traditional Chinese medicine (TCM)-including single herbs (eg, Astragalus membranaceus, Lycium barbarum), herbal formulas (eg, Xiaoyaosan, Xiaochaihu Decoction), and acupuncture-alleviates depression via the GBA, focusing on neuroscience-relevant mechanisms (inflammation, neurotrophy). A systematic literature search was conducted on PubMed, China National Knowledge Infrastructure (CNKI), and Embase from database inception to July 2025. Keywords included ["Traditional Chinese Medicine" or "TCM" or "herb" or "herbal extracts" or "Chinese herbal formulas"], ["depression" or "Depressive like behavior"], ["immune regulation"], ["inflammatory reaction"], ["neuroregeneration" or "nerve" or "neurotransmitter"]. Including peer-reviewed studies on human/animal models, articles that do not meet the requirements are excluded. A total of 307 eligible studies were included. TCM regulates gut microbiota composition-eg, increasing Lactobacillus and Bifidobacterium while reducing pathogenic taxa. Mechanistically, TCM inhibits pro-inflammatory pathways: herbs (eg, Astragalus membranaceus) and formulas (eg, Xiaoyaosan) downregulate IL-6, TNF-α, and IL-1β via suppressing NLRP3 inflammasome and TLR4/NF-κB signaling. They also enhance anti-inflammatory IL-10, elevate neurotransmitters (5-HT, DA), and upregulate BDNF. Acupuncture mirrors these effects, reducing plasma IL-6/TNF-α and restoring microbial balance to improve depressive behaviors. TCM alleviates depression by integrating gut microbiota modulation, inflammatory suppression, and neuroprotection through the GBA. This review highlights TCM's potential as a safe, alternative therapy for depression and identifies directions for standardized, large-scale clinical validation. Show less

Individuals differ in their sensitivity to external stimuli. The Highly Sensitive Child (HSC) scale can be used to measure sensitivity in children and adolescents. However, the German version has yet to be validated. We examined the psychometric properties of the German self- and the parent report version of the HSC. Measurement invariance (MI) across age groups was tested for the parent report version and latent profile analysis (LPA) was used to identify sensitivity groups. Pooled data from German-speaking countries ( The online version contains supplementary material available at 10.1007/s12144-026-09244-w. Show less

Patients with type 2 diabetes mellitus (T2DM) face a significantly elevated risk of developing cognitive impairment (CI), which has been recognized as an independent risk factor for dementia. Current glucose-lowering medications are limited by poor central nervous system penetration, delayed intervention, and single-target approaches, highlighting an urgent need for safe and effective complementary strategies. Exercise therapy, leveraging its advantage in "metabolic-neural bidirectional regulation," demonstrates considerable potential in ameliorating T2DM-related CI. This article systematically reviews basic and clinical research from the past decade, revealing that: ① Aerobic exercise, Tai Chi, and dual-task training can all significantly improve global cognitive scores (MoCA, MMSE), with effect sizes increasing over longer intervention periods; ② Tai Chi yields the most comprehensive benefits in memory, executive function, and balance-fall prevention, with an adherence rate as high as 79.6%; ③ Exercise exerts its effects through multi-target mechanisms, including upregulation of BDNF/IGF-1, suppression of IL-6/TNF-α, restoration of blood-brain barrier integrity, remodeling of the gut microbiota-butyrate-brain axis, and enhancement of mitophagy. Future research should focus on large-sample, multi-center, long-term follow-up studies to establish personalized exercise prescriptions based on genetic-metabolic-microbiota profiles. Integrating digital health technologies will enable remote monitoring and precise implementation, thereby providing an evidence-based foundation for constructing an integrated "metabolic-cognitive" prevention and treatment model. Show less

Although traditional rehabilitation training can partially improve motor function in patients with post-stroke motor disorders, its impact on neural plasticity remains limited. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method targeting the auricular branch of the vagus nerve, represents a promising neuromodulatory approach. This prospective study aimed to assess the therapeutic effects of taVNS on functional recovery in this population. A total of 147 patients with post-stroke motor disorders were consecutively enrolled between February 2023 and November 2024. After excluding 8 dropouts, 139 patients were randomly assigned via a random number table to either an electrical stimulation group (taVNS group) or a rehabilitation group (conventional training). The taVNS group initially included 73 patients, with 3 dropouts yielding a final sample of 70. The rehabilitation group initially included 74 patients, with 5 dropouts resulting in 69 participants. All participants underwent comprehensive assessments at baseline and following a 4-week intervention period. Outcome measures encompassed neuroelectrophysiological parameters (motor evoked potential latency and amplitude), clinical functional evaluations (Action Research Arm Test, Fugl-Meyer Assessment for Upper Extremity, Modified Barthel Index), serum biomarker levels (brain-derived neurotrophic factor, S100 calcium-binding protein β), and systematic documentation of adverse events. Based on post-treatment Fugl-Meyer Assessment-Upper Extremity (FMA-UE) scores, patients were further categorized into improvement and non-improvement subgroups for additional comparative analysis. Pearson correlation analysis was utilized to examine potential relationships between functional scores, neurophysiological data, and biomarker concentrations. Baseline characteristics were comparable between groups ( taVNS is an effective and safe adjunctive therapy for post-stroke motor recovery. It enhances neuroelectrophysiological function, improves motor and daily living abilities, and favorably modulates biomarkers of neural injury and repair. The consistent correlations among functional, neurophysiological, and biochemical outcomes highlight an integrated recovery pathway, supporting the integration of taVNS into standard neurorehabilitation protocols. Show less

Traumatic spinal cord injury (SCI) induces neuronal apoptosis and neuroinflammation, which exacerbate secondary damage and hinder functional recovery. Efficient clearance of apoptotic cells and modulation of the inflammatory microenvironment of spinal cord are essential for promoting tissue repair. This study aimed to investigate whether Midkine (MDK), a heparin-binding growth factor, facilitates functional recovery after SCI and explores the underlying mechanisms. A rat model of moderate SCI was established using Allen's impact method. Lentiviral vectors were used to overexpress MDK in the spinal cord. Behavioral assessments, including BBB score and gait analysis, were performed to evaluate motor function recovery. Motor evoked potentials (MEPs) serve as a neurophysiological tool for evaluating the functional integrity of the corticospinal tract. In vivo and in vitro experiments were conducted to assess microglial efferocytosis and elucidate the underlying molecular mechanisms. Transcriptomic bioinformatic analysis suggests that SCI is characterized by pronounced accumulation of apoptotic cells and robust neuroinflammatory responses, whereas single-cell analysis implicates MDK as a key contributor to neurorepair after SCI. MDK expression is dynamically regulated following SCI, with an early upregulation followed by a gradual decline over time, its location predominantly observed around microglial cells. Functionally, MDK overexpression significantly enhances motor recovery after SCI, accompanied by reduced neuroinflammation, decreased neuronal apoptosis, and improved neuroprotection. Mechanistically, MDK promotes microglial efferocytosis both in vivo and in vitro, activates the AKT/mTOR signaling pathway, upregulates BDNF and LRP-1 expression, and facilitates microglial polarization toward an anti-inflammatory M2 phenotype. Notably, inhibition of LRP-1 with receptor-associated protein (RAP) abolished the efferocytic and neuroprotective effects of recombinant MDK, highlighting LRP-1 as a key mediator of MDK's actions in microglia. Our study unveils the MDK/LRP-1/efferocytosis axis as a previously unrecognized therapeutic target for SCI. By orchestrating apoptotic cell clearance, dampening neuroinflammation, and fostering neuroprotection, this axis critically shapes the post-injury microenvironment to facilitate recovery. These findings suggest that MDK-centered therapy may represent a strategy for spinal cord repair, with LRP-1 modulation offering precise control over microglial responses. Show less

While physical inactivity represents a global health concern, the relationship between structured sports participation and overall physical activity patterns remains unclear. This study examined whether football practice enhances adherence to physical activity guidelines and influences lifestyle activity patterns beyond structured practice sessions. Twenty-seven participants [football players (EG) Show less

Ketamine holds promise for the treatment of post-traumatic stress disorder (PTSD), but challenges remain in delivery and sustained effects. This controlled study evaluates a novel intranasal formulation, employing AmyloLipid nanovesicles (ALN) to enhance ketamine's therapeutic efficacy in a predator-scent stress (PSS) rat model of PTSD. A total of 130 rats underwent PSS or sham-PSS exposure, followed by intranasal administration of ketamine-ALN (4.8, 2.4, 1.2 and 0.6 mg/kg), unloaded-ALN, saline, or standard ketamine three times weekly for two weeks, starting seven days post-trauma. Behavioral assessments, including the elevated plus maze, acoustic startle response, and contextual freezing tests, were complemented by immunohistochemical and Golgi-Cox analyses of hippocampal and paraventricular nucleus (PVN) tissues. Low-dose ketamine-ALN (0.6 mg/kg) significantly reduced anxiety-like behaviors, hyperarousal, and the prevalence of PTSD-like responses (extreme behavior responses) by 45% compared to unloaded-ALN controls. Unlike standard ketamine, ALN-mediated delivery bypassed the blood-brain barrier, enhancing bioavailability and sustaining therapeutic benefit. Mechanistically, ketamine-ALN normalized the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels-which were upregulated in the CA1 stratum lacunosum-moleculare (SLM) post-PSS-thereby stabilizing neuronal excitability. This normalization of HCN1, critical for regulating neuronal excitability and membrane potential, was accompanied by increased levels of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY), enhancing neuroplasticity and dendritic complexity. These findings demonstrate that ALN-based intranasal delivery of ketamine is more effective than standard administration, particularly at low doses. The results suggest that low-dose ketamine-ALN modulates a hippocampal circuit involving HCN1, BDNF, and NPY to foster adaptive stress responses. Collectively, ketamine-ALN represents a promising targeted therapy for PTSD, with HCN1 channels as a key mediator of stress-induced neuronal dysfunction and ketamine's therapeutic action, thus advancing the prospects for precision treatment of stress-related disorders. Show less

Pituitary macroadenomas often cause visual pathway impairment due to optic chiasm compression. The association between systemic neurotrophic factors and visual recovery remains insufficiently explored. This prospective observational cohort study included 53 patients (106 eyes); 36 patients (72 eyes) completed a 12-month follow-up. Patients were assigned to a treatment group (surgical and/or pharmacological; Show less

This narrative review systematically synthesizes recent clinical and pre-clinical evidence to elucidate the latest neurobiological mechanisms underlying acupuncture for post-stroke insomnia combined with cognitive impairment (PS-ICI). PS-ICI is characterized pathologically by a hippocampal-prefrontal circuitry-mediate "sleep-cognition vicious cycle" and clinically by concurrent cognitive decline and sleep-architecture disruption, both of which markedly impede post-stroke neurological recovery. Grounded in the Traditional Chinese Medicine (TCM) principle of "regulating Shen and re-animating the brain, "acupuncture exerts bidirectional modulation on cognition and sleep, significantly improving core functional outcomes and activities of daily living. Up-to-date studies confirm that synergistic, multi-dimensional effects are achieved through regulation of the BDNF-TrkB-PI3K/Akt signaling axis, preservation of neurovascular unit integrity, restoration of gut-brain axis homeostasis, normalization of circadian immune rhythms, and reshaping of default-mode network (DMN) plasticity. Given the high heterogeneity of included studies, a qualitative integrative approach was employed. Current evidence is nevertheless limited by small sample sizes, short follow-up durations, and substantial heterogeneity in acupuncture parameters (frequency and point selection); future work must therefore focus on dissecting inter-pathway interactions, standardizing therapeutic protocols, and integrating multi-omic technologies to propel acupuncture toward precision, evidence-based management of PS-ICI. Show less

The intestine acts as the primary site for absorption of dietary lipids. These lipids are packaged and transported via lipoprotein complexes, whose altered levels correlate with metabolic disease.  The Show less

Innate lymphoid cells (ILCs) are rare, tissue-resident innate lymphocytes that functionally mirror CD4+ T helper cell lineages but lack antigen receptors. Type 3 ILCs (ILC3s) are enriched in the gut, airways, and mucosal lymphoid tissues, where they regulate inflammation and promote barrier integrity. To define the regulatory architecture of primary human ILC3s, we map promoter-anchored chromosomal contacts using high-resolution, low-input Promoter Capture Hi-C (PCHi-C) in these cells alongside CD4+ T cells. By combining statistical detection with a PCHi-C-adapted Activity-by-Contact approach, we link promoters to distal regulatory elements, identifying hundreds of ILC3-specific contacts. We use these maps to connect genome-wide association study (GWAS) risk variants for Crohn's disease to target genes using multiCOGS, a Bayesian framework that integrates PCHi-C with summary-statistic imputation and multivariate fine-mapping. This analysis highlights both known and unanticipated candidates, including Show less

While a growing body of literature suggests a role for infections in Alzheimer's disease (AD), microbial contributions to AD remains a contentious topic, in part due to challenges in reconciling the positive evidence with studies reporting null findings. Here, we examine the evidence that argues against a role for infections in AD, while offering mechanistic hypotheses that may account for both the negative and positive findings, including dysregulated host immunity and gene-environment interactions of AD-associated genes. Show less

Mild behavioral impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we cross-sectionally describe the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. Show less

Neuronal ceroid lipofuscinosis type 3 (CLN3) disease is a rare, life-limiting pediatric neurodegenerative disorder with no approved disease-modifying therapy. We conducted a prospective case report from October 2023 to April 2025 involving two female siblings with genetically confirmed CLN3 disease (homozygous for the common 1 kb deletion). Both patients were treated with oral, weight-based miglustat for 18 months. Miglustat was supplied as off-label use in the absence of a therapeutic alternative for this severe neurodegenerative disorder. Clinical outcomes were assessed using comprehensive ophthalmologic evaluation, the Unified Batten Disease Rating Scale (UBDRS), and the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). At the time of report, patients were aged 13 and 10 years. Both had been diagnosed at age 7 years and commenced miglustat at ages 11 and 9 years, respectively. Over the treatment period, both patients demonstrated improvement in visual acuity and clinical stabilization on the Unified Batten Disease Rating Scale. One patient showed measurable improvement in adaptive functioning as assessed by Vineland-3. No significant adverse effects were reported. These preliminary findings suggest potential short-term clinical benefit of miglustat in pediatric patients with CLN3 disease, particularly when initiated early in the disease course. Further studies involving larger cohorts and longer follow-up are warranted to evaluate the safety and long-term efficacy of miglustat in this population. Show less

To investigate the association between quantitative retinal vascular parameters and coronary artery disease (CAD) and to evaluate the efficacy of a retinal phenotype-based diagnostic model as a non-invasive tool for early CAD screening. A retrospective cross-sectional study. A single-centre study conducted at the Cardiovascular Center of Beijing Tongren Hospital, Capital Medical University, China, between January and October 2024. 417 patients with suspected angina undergoing their first coronary angiography (CAG) were enrolled. Inclusion criteria were age >18 years and high-quality fundus photography within 24 hours pre-CAG. Major exclusions were prior coronary interventions, severe systemic/valvular heart diseases and ocular conditions impairing retinal vascular visualisation. The primary outcome was the association between quantitative retinal vascular parameters and the presence of CAD (defined as ≥50% stenosis). Secondary outcomes included the diagnostic performance area under the receiver operating characteristic curve (AUROC) of three predictive models: one based on quantitative retinal vascular parameters alone, one based on traditional risk factors and a combined model integrating both retinal and clinical variables. This study enrolled 417 patients undergoing initial CAG. Compared with non-CAD controls (n=190), patients with CAD (n=227) had higher prevalence of hypertension, dyslipidaemia and diabetes, along with elevated levels of fasting blood glucose, lipoprotein(a) (Lp(a)), triglyceride (TG) and glycated haemoglobin (HbA1c) (all p<0.05). Quantitative fundus analysis revealed that multiple retinal vascular parameters were independently associated with CAD after multivariable adjustment, including fractal dimension (FD), vessel density (VD) and specific zonal measures of vessel diameter and tortuosity (all p<0.05). Multivariable logistic regression incorporating both fundus and clinical variables identified the following independent predictors of CAD: a decrease in FD (OR=0.26, 95% CI 0.16 to 0.41, p<0.01), reduced optic disc long-to-short axis ratio (OR=0.04, 95% CI 0.004 to 0.46, p=0.01) and optic disc-to-macula distance (OR=0.91, 95% CI 0.86 to 0.97, p<0.01), male sex, dyslipidaemia and elevated levels of Lp(a), TG, low-density lipoprotein cholesterol and HbA1c (all p<0.05). The final diagnostic model achieved an AUROC of 0.802 (95% CI 0.76 to 0.845), with a sensitivity of 0.797 and a specificity of 0.679 at the optimal cut-off. Internal validation via bootstrap resampling (1000 iterations) confirmed the robustness of the identified predictors. Our findings, derived from an artificial intelligence-based fully automated quantitative retinal vascular parameters measurement method, revealed that multiple quantitative fundus parameters-including FD, VD and other morphological parameters were significantly associated with CAD risk. The CAD diagnostic model we developed demonstrates strong performance and high interpretability, making it suitable for early CAD screening and diagnosis. Show less

Mind-body exercises (MBEs), including Tai Chi (TC), Qigong (QG), Yoga (YG), and Mindfulness-Based Stress Reduction (MBSR), show promise in neuropsychiatric rehabilitation by modulating neuroinflammation. This study systematically examines the effects of MBEs on neuroinflammation-related biomarkers in neuropsychiatric disorders, aiming to identify optimal modalities, dosages, and key moderators. Databases were systematically searched for eligible RCTs from inception until February 2025. Data were analyzed using R packages (" Twenty-nine RCTs involving 2253 participants were included. MBEs significantly reduced IL-6 [standardized mean difference (SMD) = -0.47] and IL-1β [SMD = -0.90], while increasing BDNF [SMD = 1.08] and IL-10 [SMD = 0.87]. Effects on TNF-α [SMD = -0.33] and CRP [SMD = -0.12] showed a non-significant trend toward benefit. Dosages between 600 and 1000 MET-min/week yielded the most pronounced anti-inflammatory effects. Network meta-analysis ranked TC and MBSR as the most effective for reducing proinflammatory cytokines, while QG showed the greatest benefits for neurotrophic outcomes. Participant characteristics (age, population, clinical conditions) and MBE parameters (duration, frequency, session length) significantly moderated neuroprotective effects. MBEs effectively reduce proinflammatory cytokines (IL-1β, IL-6) and enhance anti-inflammatory cytokine (IL-10) and neurotrophic factor (BDNF) in neuropsychiatric disorders. The optimal dosage ranges from 600 to 1000 MET-min/week. Given the impact of participant characteristics and MBE parameters, personalized prescriptions may enhance clinical outcomes and long-term neuroprotective effects. Show less

Falls have long been a significant safety concern worldwide, not only compromising the physical and psychological health of older adults and limiting their social engagement but also imposing substantial economic and caregiving burdens. Evidence on fall risk perception among Chinese community-dwelling older adults remains limited, especially for those transitioning to community living after hospital discharge. This research examined the subtypes of fall risk perception of Chinese community-dwelling older adults in the post-discharge transition and to explore subgroup characteristics and associated factors. A cross-sectional survey was conducted between January 2024 to March 2025 in Hangzhou, Zhejiang Province. A self-designed questionnaire was used to collect demographic and health-related information, The Fall Risk Perception Scale for Community-dwelling Older Adults was used to assess the fall risk perception, the objective fall risk was assessed by Morse Fall Scale. Latent profile analysis (LPA) was performed to extract latent classes of fall risk perception, and multinomial regression analyses were used to identify differences between these categories. A total of 468 older adults were included, with 56.0% were male. Three fall risk perception subtypes were identified by LPA: Low Perception-Social Context Desensitized Type (29.2%), Moderate Perception - Balanced Type (43.4%), and High Perception - Bio-behaviorally Salient Type (27.4%). Individuals who were aged with 70-79 (OR = 0.46, 95% CI: 0.27-0.77), with college education or above (OR = 0.31, 95% CI: 0.13-0.76), those who underwent surgery during hospitalization (OR = 0.26, 95% CI: 0.15-0.43), reported difficulty falling asleep (OR = 0.40, 95% CI: 0.20-0.82), and those with a history of falls (OR = 0.44, 95% CI: 0.24-0.81) were significantly more likely to be in the High Perception - Bio-behaviorally Salient Type. Compared to objective fall risk level, a third of participants (31.4%) correctly estimated their fall risk, 23.1% overestimated it and 45.5% underestimated it. Most older adults possess a Moderate Perception - Balanced Type toward fall risk. Key determinants of heightened risk perception included advanced age, higher education, fall history, and recent surgical experience. Tailored, profile-specific risk communication strategies are essential to improve perceptual accuracy during the hospital-to-home transition may support post-discharge fall prevention. Show less