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Background Freezing of gait is a debilitating symptom of Parkinson’s disease associated with high risks of falls and poor quality of life. While productive therapy for FoG is still underway, early prediction of FoG could help high-risk PD patients to take preventive measures. In this study, we predicted the onset of FoG in de novo PD patients using a battery of risk factors from patients enrolled in PPMI cohort. Methods Baseline characteristics were compared between subjects who developed FoG (68 patients, 37.2%, pre-FoG group) during the five-year follow up and subjects who did not (115 patients, 62.8%, non-FoG group). A multivariate logistic regression model was built based on backward stepwise selection of factors that were associated with FoG onset in the univariate analysis. ROC curves were used to assess sensitivity and specificity of the predictive model. Results At baseline, age, PIGD score, cognitive functions, autonomic functions, sleep behavior, fatigue and striatal DAT uptake were significantly different in the pre-FoG group relative to the non-FoG group. However, there was no difference in genetic characteristics between the two patient sets. Univariate analysis showed several motor and non-motor factors that correlated with FoG, including PIGD score, MDS-UPDRS part II score, SDMT score, HVLT Immediate/Total Recall, MOCA, Epworth Sleepiness Scale, fatigue, SCOPA-AUT gastrointestinal score, SCOPA-AUT urinary score and CSF biomarker Abeta 42 . Multivariate logistic analysis stressed that high PIGD score, fatigue, worse SDMT performance and low levels of Abeta 42 were independent risk factors for FoG onset in PD patients. Conclusions Combining motor and non-motor features including PIGD score, poor cognitive functions and CSF Abeta can identify PD patients with high risk of FoG onset.

Background Chronic diseases pose substantial healthcare burdens globally, notably in aging nations like China. Internet Medical Services (IMS) demonstrate significant potential to mitigate healthcare challenges in chronic disease management through optimized resource allocation and enhanced remote care capabilities. However, persistent adoption disparities and the “high demand–low penetration” paradox highlight persistent barriers stemming from the digital divide. This study aims to investigate factors influencing IMS utilization among chronic disease patients, examining their effects across specific IMS domains and acceptance pathways, thereby offering new insights for optimizing chronic disease management. Methods This study extended the Technology Acceptance Model (TAM) by integrating eHealth literacy and Technology anxiety to evaluate the utilization of IMS among 520 patients with chronic diseases in Jinan, China. IMS was categorized by functional domains (Information Access, Convenience Services, Online Health) and utilization stages (Awareness, Want, Adoption). The dual-method analysis: Awareness-Want-Adoption Gap (AWAG) matrix for service-specific disparity mapping and Structural Equation Modeling (SEM) to quantify perceptual drivers, providing a panoramic perspective to deconstruct the complex utilization. Results Information Access IMS showed the highest acceptance, while Online Health exhibited severe Want-to-Adoption collapse (71.43% gap). Affluent patients demonstrated paradoxical rejection of Online Health despite high Awareness. SEM confirmed Perceived Usefulness (β = 0.338–0.423, P  < 0.001) and eHealth literacy (β = 0.184–0.395, P  < 0.001) are significant and direct drivers of IMS utilization, with stage-specificity observed across the utilization process. Matrix analysis identified critical barriers for vulnerable subgroups: rural residents, elders (≥ 70 years), and low-education (≤ 9 years) patients. Conclusions IMS adoption is governed by multidimensional determinants beyond access, including cognitive, socio-economic, and other factors. Counterintuitive patterns (e.g., affluent patients’ rejection of Online Health) necessitate tiered interventions, such as eHealth literacy programs for vulnerable groups, service standardization to mitigate distrust, and regulatory frameworks to ensure data security. This study’s dual-method framework (matrix analysis and SEM) critically delineated barrier typologies through staged decomposition, establishing an evidence-based scaffold for optimizing digital health equity.

The rational design of heterogeneous catalysts with hierarchical nanostructures and large surface areas is crucial for enhancing active site accessibility and improving catalytic efficiency. In this context, we report the synthesis of a novel, recyclable nanocatalyst composed of Lu₂CrMnO₆ nanoparticles anchored onto pyrimidine grafted graphitic carbon nitride nanosheets (Pm-g-C₃N₄), which are uniformly immobilized on dendritic fibrous nanosilica (DFNS). The integration of DFNS provides a highly porous, open channel framework rich in surface hydroxyl groups, facilitating strong chemical bonding with Pm-g-C₃N₄ and ensuring stable immobilization of the Lu based perovskite phase. This hierarchical DFNS/Pm-g-C₃N₄@Lu₂CrMnO₆ nanocomposite was synthesized through a straightforward, environmentally friendly route and exhibits excellent structural integrity, high dispersion of active Lu₂CrMnO₆ sites, and efficient charge transfer characteristics. Under solvent-free conditions, the catalyst effectively promotes the three component coupling of CO₂, α-amino acids, and ethylene oxide, yielding N-[(2-hydroxyethoxy)carbonyl]glycine with remarkable selectivity and yield under mild reaction parameters. The system demonstrates outstanding recyclability over multiple cycles with negligible activity loss, making it an attractive candidate for sustainable CO₂ conversion. The synergistic effects of the Lu₂CrMnO₆ perovskite, nitrogen rich g-C₃N₄ functionality, and the high surface area DFNS support contribute to the superior catalytic behavior. Overall, the DFNS/Pm-g-C₃N₄@Lu₂CrMnO₆ platform offers promising prospects for green CO₂ fixation technologies relevant to materials science.

Colon adenocarcinoma (COAD) is a lethal malignancy with a poor prognosis. The tumor microenvironment (TME) is pivotal in its development, within which lactate accumulation is a common metabolic hallmark. Lactylation, a novel post-translational modification driven by lactate, serves as a crucial link between tumor metabolism and immunosuppression. It plays multifaceted roles in promoting malignant progression, immune evasion, and chemoresistance. Therefore, systematically investigating lactylation and identifying its key mediators may yield novel therapeutic targets and strategies for COAD. We performed an integrative multi-omics analysis of lactylation-related genes (LRGs) in COAD and pan-cancer cohorts, leveraging bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic data from public repositories including TCGA and GEO. A curated set of 160 LRGs was investigated using a multi-step machine learning framework, integrating Cox regression, time-dependent ROC analysis, and optimal risk stratification to construct robust prognostic signatures, which collectively identified AARS2 as a pivotal candidate. Subsequent multi-faceted oncogenic characterization of AARS2 encompassed its expression profiles, diagnostic and prognostic value, and associations with tumor microenvironment heterogeneity. To validate AARS2 at the protein level, we first interrogated the HPA database and subsequently confirmed its expression using immunohistochemistry (IHC) on an independent cohort of clinical COAD specimens. To further elucidate AARS2's functional role in COAD pathogenesis and its potential linkage to lactylation biology, validation was performed using the human COAD cell line HCT116. AARS2 expression was confirmed at both protein (Western blot) and mRNA (qRT-PCR) levels. qRT-PCR additionally quantified transcriptional changes in immune-related genes (CCL5, CXCL10, IFNB1), while extracellular lactate accumulation was measured to assess AARS2-associated metabolic alterations. All statistical analyses were performed in R, with a significance threshold of p < 0.05. Integrative multi-omics analyses identified AARS2 as significantly upregulated in COAD and multiple malignancies, with elevated expression correlating with adverse clinical outcomes. Single-cell and spatial transcriptomic profiling indicated predominant enrichment of AARS2 in malignant cell populations and association with immunosuppressive microenvironment features. Functional enrichment suggested potential involvement in epithelial-mesenchymal transition, hypoxia response, and cell cycle pathways. Immunohistochemical validation in clinical COAD specimens confirmed higher AARS2 protein levels in tumor tissues versus adjacent normal mucosa; concurrent elevation of cGAS protein was observed, though functional activity requires contextual interpretation. studies in HCT116 cells revealed that AARS2 knockdown reduced extracellular lactate accumulation and attenuated global protein lactylation. Concomitantly, transcriptional upregulation of cGAS-STING pathway-associated genes (CCL5, CXCL10, IFNB1) was observed following AARS2 silencing. These correlative findings suggest a potential nexus between AARS2, lactate metabolism, protein lactylation dynamics, and innate immune signaling modulation in COAD. AARS2 correlates with lactylation dynamics, metabolic features, and immune modulation in COAD, suggesting a potential role in lactylation-associated cGAS-STING pathway regulation. These correlative observations warrant rigorous mechanistic validation to define causality and assess translational potential.

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.

To optimize the modifying effect of inorganic additives by using organic modifier, this study selected layered double hydroxides (LDHs) and ultraviolet (UV) absorbers as anti-aging agents to prepare modified asphalt. The anti-aging performance of modified asphalt was evaluated using a weathering tester. The influence of the composite modification effects of organic–inorganic modifiers on the pavement performance of asphalt binders was investigated through conventional tests. Dynamic shear rheometer tests were conducted to examine the performance grade classification of the composite anti-aging-modified asphalt. Fourier transform infrared spectroscopy was employed to analyze the variations in functional group composition of the composite-modified asphalt. Furthermore, molecular dynamics simulations were utilized to elucidate the changes of composite-modified asphalt at the molecular level under UV aging. The results indicate that the incorporation of UV absorbers significantly mitigates the adverse effects of LDHs on the physical properties of asphalt, while their synergistic modification enhances the anti-aging performance of the modified asphalt. Due to the addition of UV absorbers, the solubility difference between the composite modifier and asphalt improves compared to that of LDHs alone. Moreover, as the proportion of UV absorbers increases, the solubility difference gradually decreases, enhancing the thermal stability of the asphalt system.

Abstract BACKGROUND Subthalamic nucleus (STN) and globus pallidus interna (GPi) are the most effective targets in deep brain stimulation (DBS) treatment for Parkinson disease (PD). However, the individualized selection of targets remains a clinical challenge. OBJECTIVE To combine unilateral STN and contralateral GPi stimulation (STN DBS in one brain hemisphere and GPi DBS in the other) to maximize the clinical advantages of each target while inducing fewer adverse side effects in selected patients with PD because each target has its own clinical effects and risk profiles. METHODS We reviewed the clinical outcomes of 8 patients with idiopathic PD treated with combined unilateral STN and contralateral GPi DBS. Clinical outcome assessments, focusing on motor and nonmotor symptoms, were performed at baseline and 6-mo and 12-mo follow-up. We performed the assessments under the following conditions: medication on and off (bilateral stimulation on and off and unilateral STN stimulation on). RESULTS Patients showed a significant improvement in motor symptoms, as assessed by the Unified Parkinson Disease Rating Scale III (UPDRS-III) and Timed Up-and-Go Test (TUG), in the off-medication/on-stimulation state at 6-mo and 12-mo follow-up. Also, patients reported a better quality of life, and their intake of levodopa was reduced at 12-mo follow-up. In the on-medication condition, bilateral stimulation was associated with an improvement in axial symptoms, with a 64% improvement in measures of gait and falls at 12-mo follow-up. No irreversible adverse side effects were observed. CONCLUSION Our findings suggest that combined unilateral STN and contralateral GPi DBS could offer an effective and well-tolerated DBS treatment for certain PD patients. Graphical Abstract Graphical Abstract

Therapeutic options for refractory depression are urgently needed. We conducted a deep brain stimulation (DBS) randomized controlled trial of the bed nucleus of the stria terminalis (BNST), an extended amygdala structure, and nucleus accumbens (NAc) in 26 refractory depression patients to assess treatment efficacy and predictors of response. BNST-NAc DBS had a 50% depression response rate and 35% remission rate in the open-label phase. We identified an objective intracranial physiological biomarker using acute and chronic intracranial recordings, machine learning, and an integrated framework combining electrophysiology, neuroimaging, and behavior: lower BNST theta and prefrontal-BNST coherence with top-down connectivity predicted better depression outcomes and quality-of-life after chronic stimulation at 3, 6 and 12 months, confirmed across eyes -open and -closed states and machine learning. We identified a physiology-guided connectivity network involving dorsal anterior cingulate and lateral inferior frontal cortex tracts. These biomarkers, linked to negative emotional bias and anxiety, highlight the efficacy of BNST-NAc DBS for refractory depression and has potential broader clinical implications. ClinicalTrials.gov registration: NCT04530942. This study identifies BNST theta and prefrontal BNST coherence as intracranial biomarkers predicting depression outcomes after DBS. Lower activity predicted better long-term benefit, linking brain circuits to emotional bias and anxiety.

Background Postural abnormalities (PA) are common in the advanced stages of Parkinson’s disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. Methods T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. Results Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. Conclusions Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. Trial registration Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

Subthalamic nucleus (STN) and globus pallidus interna (GPi) are two main structures primarily targeted by deep brain stimulation (DBS) to treat advanced Parkinson's disease (PD). A subset of cases with unsatisfactory outcomes may benefit from rescue DBS surgery targeting another structure, while these patients' characteristics have not been well described and this phenomenon has not been well reviewed. This monocentric retrospective study included patients with PD, who underwent rescue STN DBS following an unsatisfactory outcome of the initial bilateral GPi DBS in a retrospective manner. A short review of the current literature was conducted to report the clinical outcome of rescue DBS surgeries. Eight patients were identified, and six of them were included in this study. The rescue STN DBS was performed 19.8 months after the initial GPi DBS. After 8.8 months from the rescue STN DBS, patients showed a significant off-medication improvement by 29.2% in motor symptoms compared to initial GPi DBS. Non-motor symptoms and the health-related quality of life were also significantly improved. Our findings suggest that the rescue STN DBS may improve off-medication motor and non-motor symptoms and quality of life in patients with failure of initial GPi DBS. The short review of the current literature showed that the target switching from GPi to STN was mainly due to poor initial outcomes and was performed by target substitution, whereas the switching from STN to GPi was mainly due to a gradual waning of benefits, long-term axial symptoms, dyskinesia, and dystonia and was performed by target addition.